WO2026006808A1 - Hydroxylamine nitric oxide donors for thermally induced delivery of inhalable nitric oxide - Google Patents

Abstract

Provided are thermo-responsive nitric oxide (NO) releasing molecules ("donors") and their use with polymer delivery systems. The delivery systems may include devices that allow for delivery of a dose of NO for inhalation such as portable inhalation devices. The compositions and methods may be used in the treatment of pulmonary conditions such as pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, and asthma. In some aspects, the compositions and methods provide a portable NO delivery mechanism allowing safe and pure NO administration outside of as well as in hospital settings.

Description

HYDROXYLAMINE NITRIC OXIDE DONORS FOR THERMALLY INDUCED DELIVERY OF INHALABLE NITRIC OXIDE CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to and benefit of U.S. Provisional Patent Application No. 63/665,853 filed June 28, 2024. The contents of which are incorporated herein in their entirety FIELD OF THE DISCLOSURE [0002] The present disclosure provides nitric oxide (NO) donors for thermally induced delivery of inhalable nitric oxide. BACKGROUND OF THE DISCLOSURE [0003] Inhaled nitric oxide (iNO) can be used to treat a variety of disorders affecting pulmonary systems such as pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma among others. It is also a potent antimicrobial agent. [0004] Current commercial iNO delivery systems deliver iNO as a dilute gas (2-160 ppm) from more concentrated NO gas tanks. These compressed gas cylinders and associated delivery systems are costly, difficult to transport, and dangerous, limiting iNO administration to well controlled hospital settings. Alternative on-demand delivery systems have focused on NO generation via corona discharge, photolysis, and catalytic reduction of higher NOx. However, many of these delivery systems do not currently meet demands for portability and NO purity, or rely on toxic and/or explosive NO precursors. Thus, a need for generation of medical-grade nitric oxide using delivery systems with small form factors and low power demands remains. SUMMARY OF THE DISCLOSURE [0005] The current disclosure provides thermo-responsive nitric oxide releasing compounds (“donors”) based on N-trityl 3,6-dihydro-1,2-oxazines, allyl hydroxylamine, methods of synthesizing such compounds, and their use with delivery systems to provide inhaled nitric oxide (NO). In some aspects, the compositions and methods described herein provide inhaled nitric oxide systems that can be stored for extended periods with minimal loss of NO delivery activity. [0006] In some aspects, the thermo-responsive hydroxylamine nitric oxide (NO) releasing compounds have structures including that of Formula I, II, or III: R₅ R₆ wherein R₁ comprises an atom bound to N wherein a weak bond is formed, and R₁, R₂, R₃, R₄, R₅, R_6, and R₇ are independently H or an organic molecule. In some aspects, R₁ is hydrogen, substituted or unsubstituted C_1-20-alkyl, substituted or unsubstituted C_3-8-cycloalkyl, wherein in each C_1-20-alkyl-, C_3-8-cycloalkyl-, one CH₂ group may optionally be replaced by CO, SO or SO₂, SO₃, SiR^N2 one CH₂ group optionally by O or NR^N and one H group optionally by C₁-C₂₀ aryl, heteroaryl, or alkyl groups, halogens, OR, or NR^N where R is hydrocarbon and superscript “N” is a whole number. R₁ may also be a hydrocarbon polymer. In some aspects R₁ may be a reactive non-metal or an alkyl or cycloalkyl substituted with reactive non-metals such as H, C, N, O, P, S, and Se. In embodiments, R₂-R₇ may be a wide range of chemical motifs as they do not directly participate in bond forming and breaking reactions resulting in the release of NO. For example, R2, R3, R4, R5, R6, and R7 of Formula I and R2, R3, R4, R5, and R6 of Formulas II and III may independently be selected from an alkyl group, alcohol, aldehyde, a carboxylic acid, esters nitrile, an aromatic group, an ether, an amine, amide, silane, phosphine, thiol, thioether, or a halide. [0007] In some aspects, the NO-releasing molecule may be cast in a polymer, including a porous polymer, to create an amorphous solid dispersion. Such casting may allow for covalent and non- covalent bonding of the NO-releasing molecule to the polymer. In some aspects, release of NO from the molecule and/or the amorphous solid dispersion may be controlled or modified by the application of heat. While a variety of heating and administration systems may be used, in some aspects, the NO-releasing molecule may be administered using a handheld portable apparatus. Such a device may be presented in a variety of formats including a breathing bag, as part of continuous positive airway pressure (CPAP), through a nasal canula, or other individualized inhaled distribution systems, to allow for constant or controlled release of inhaled nitrous oxide (iNO). [0008] In embodiments, the disclosure includes inhaling NO released from the hydroxylamine NO releasing compounds described herein for the use in treatment of disease in a subject including a human, the diseases including diseases affecting pulmonary systems such as pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, and asthma among others. In some aspects, inhaled NO may be used as an antimicrobial agent. [0009] In embodiments, the disclosure includes methods of synthesizing trityl-diphenyloxazine including combining trityl chloride of formula of formula of formula . [0010] In embodiments, the disclosure includes methods of synthesizing 2,5-diphenyloxazine including combining (9H-fluoren-9-yl)methyl hydroxycarbamate of formula 1,3-butadiene of formula to form 2,5-diphenyloxazine of the formula . [0011] In embodiments, the disclosure includes methods of synthesizing trityl-bicyclicoxazine comprising combining trityl chloride of formula bicyclicoxazine of formula . of the foregoing and related ends, certain illustrative aspects of the NO releasing molecules and delivery systems are described herein in connection with the following description and the attached drawings. This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This summary is not intended to identify key features or essential features of any subject matter described herein. BRIEF DESCRIPTION OF THE DRAWINGS [0013] Some of the drawings submitted herein may be better understood in color. Applicant considers the color versions of the drawings as part of the original submission and reserve the right to present color images of the drawings in later proceedings. [0014] FIG. 1 is a cartoon of NO donors (NO releasing molecules) physically doped in porous supporting matrices (non-covalently bound), or chemically bonded (covalently bound) to porous polymeric matrices. [0015] FIG. 2 illustrates hydroxylamines converted to labile nitrosos via retro-cycloadditions (Class 1) and retro-ene (Class 2) reactions. [0016] FIG.3 illustrates a NO/NO2 measurement flow system with an optional activated carbon filter. [0017] FIGs.4A-4C are graphs showing thermolysis of three examples of NO releasing molecules: (FIG.4A) 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6) under N2 at 0.5L/min at 150^oC (without supporting matrix); (FIG. 4B) 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct-5-ene (Compound 3) under N2 at 0.5L/min at 110^oC (without supporting matrix); and ( FIG.4C) N-allyl- N-(tri([1,1'-biphenyl]-4-yl)methyl)hydroxylamine (Compound 10) under N2 at 0.5L/min at 190^oC (without supporting matrix). [0018] FIGs. 5A-5B. are graphs showing (FIG. 5A) photolysis of a S-nitrosothiol under N2 atmosphere and (FIG.5B) photolysis of a S-nitrosothiol under air. Higher NO2 contamination is seen due to aerobic oxidation (from Journal of Controlled Release 2020, 318, 264–269). [0019] FIGs. 6A-6D are graphs showing: (FIG. 6A) a comparison of powder X-ray diffraction patterns (PXRD) of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6) alone and combined with hyper crosslinked polymer (HCP-1) by 15 wt% using different mixing methods with only the solvent dispersed method resulting in amorphous solid dispersion (ASD) with no detectable crystalline domain; (FIG. 6B) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2- oxazine (Compound 6) under N2 at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1) as the supporting matrix, at 150^oC; and (FIG. 6C) the yield of NO via thermolysis by day since synthesis (with normal room light exposure) for 79 days of 3,6-diphenyl-2-trityl-3,6-dihydro-2H- 1,2-oxazine, 15 wt% in hyper crosslinked polymer (HCP-1) as the supporting matrix (ambient temperature and humidity) and (FIG.6D) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2- oxazine dispersed in hyper crosslinked polymer (HCP-1) by 15wt% with periodic application of heat (150 ^oC). [0020] FIGs.7A-D are graphs showing: (FIG.7A) PXRD of 3,6-diphenyl-2-trityl-3,6-dihydro-2H- 1,2-oxazine (Compound 6) alone and mixed with hyper crosslinked polymer (HCP-1-OEt) by 15 wt% through solvent dispersing showing that solvent dispersion results in loss of all detectable crystalline domains; (FIG. 7B) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6) under N₂ at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix, at 150^oC; (FIG.7C) the yield of NO via thermolysis by day since synthesis (with normal room light exposure) for 36 days of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6), 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix (stored at ambient temperature and humidity); and (FIG.7D) thermolysis of 3,6-diphenyl-2-trityl- 3,6-dihydro-2H-1,2-oxazine (Compound 6) dispersed in hyper crosslinked polymer (HCP-1-OEt) by 15 wt% with periodic application of heat (150^oC). [0021] FIGs. 8A-8C are a graphs showing: (FIG. 8A) PXRD of 3-trityl-3-oxa-3- azabicyclo[2.2.2]oct-5-ene (Compound 3) alone and combined with hyper crosslinked polymer (HCP-1) by 15wt% using different mixing methods. Only solvent dispersion results in amorphous solid dispersion (ASD); (FIG. 8B) thermolysis of 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct-5-ene (Compound 3), under N2 at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1) as the supporting matrix, at 90^oC; and (FIG.8C) the yield of NO via thermolysis by day since synthesis (with normal room light exposure) for 27 days of 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct-5-ene (Compound 3), 15 wt% in hyper crosslinked polymer (HCP-1) as the supporting matrix (stored at ambient temperature and humidity). [0022] FIGs.9A-9C are graphs showing: (FIG.9A) PXRD of 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct- 5-ene (Compound 3) alone, and combined with hyper crosslinked polymer (HCP-1-OEt) 15 wt% using solvent dispersion; (FIG. 9B) thermolysis of 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct-5-ene (Compound 3), under N2 at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix, at 90^oC; and (FIG.9C) the yield of NO via thermolysis after storage on bench (with normal room light exposure) for 35 days of 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct-5-ene (Compound 3),15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix. [0023] FIGs. 10A-10B are graphs showing: (FIG. 10A) the yield of NO via thermolysis after storage on bench (with normal room light exposure) for 28 days of S-nitroso-N-acetylpenicillamine (SNAP) 15 wt% in hyper crosslinked polymer (HCP-1) as the supporting matrix; and (FIG.10B) the yield of NO via thermolysis after storage on bench (with normal room light exposure) of 3,6- diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6), 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct- 5-ene (Compound 3), and S-nitroso-N-acetylpenicillamine (SNAP), each donor was dispersed by 15 wt% in hyper crosslinked polymer (HCP-1) as the supporting matrix. [0024] FIGs. 11A-11B are graphs showing: (FIG. 11A) thermolysis of 3,6-diphenyl-2-trityl-3,6- dihydro-2H-1,2-oxazine (Compound 6) under N₂ at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1) as the supporting matrix, at different temperatures, 90^oC, 120^oC, and150^oC; and (FIG. 11B) a larger scale (10x the quantity of FIG.6B) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro- 2H-1,2-oxazine (Compound 6) under N₂ at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP- 1) as the supporting matrix, at 150^oC. [0025] FIGs. 12A-12C are graphs showing: (FIG. 12A) thermolysis of 3,6-diphenyl-2-trityl-3,6- dihydro-2H-1,2-oxazine (Compound 6) under N₂ at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix, at different temperatures, 90^oC, 120^oC, and150^oC; (FIG. 12B) a larger scale (6x scale of FIG.7B) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2- oxazine (Compound 6) under N2 at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix, at 150^oC; and (FIG.12C) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro- 2H-1,2-oxazine (Compound 6) under N2 sweep gas at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix, under PID feedback control to maintain a consistent concentration of NO in the sweep gas. The target NO concentration is set at 2 ppm. [0026] FIGs. 13A-13D are graphs showing: (FIG. 13A) thermolysis of 3,6-diphenyl-2-trityl-3,6- dihydro-2H-1,2-oxazine (Compound 6) under N2 at 0.5L/min, 15 wt% in cross linked polystyrene (DiaionⓇ HP-20) as the supporting matrix, at 150^oC.; (FIG.13B) thermolysis of 3,6-diphenyl-2- trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6) under N₂ at 0.5L/min, 15 wt% in PAF-1 as the supporting matrix, at 150^oC; (FIG. 13C) thermolysis of TAF-3,6-dihydro-2H-1,2-oxazine (Compound 18) under N₂ at 0.5L/min, at 150^oC; and (FIG. 13D) thermolysis of Trityl resin-3,6- dihydro-2H-1,2-oxazine (Compound 19) under N₂ at 0.5L/min, at 150^oC. [0027] FIGs.14A-14B show graphs of: (FIG.14A) PXRD of 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct- 5-ene (Compound 3) in the document), and 15 wt% the donor molecule solvent dispersed in different supporting matrix showing that dispersion eliminates detectable crystalline domains; and (FIG.14B) thermolysis of 3-trityl-3-oxa-3-azabicyclo[2.2.2]oct-5-ene (Compound 3), under N2 at 0.5L/min, 15 wt% in different porous supporting matrices, at 90^oC. [0028] FIG.15 is a graph showing thermolysis of S-nitroso-N-acetylpenicillamine (SNAP) under air at 0.5L/min, 15 wt% in HCP-1 as the supporting matrix, at 120^oC. (SNAP is one of a conventional NO donor to compare). [0029] FIGs. 16A-16G are graphs showing: (FIG. 16A) thermolysis of 3,6-diphenyl-2-trityl-3,6- dihydro-2H-1,2-oxazine (Compound 6) under air at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix, at 150^oC; (FIG.16B) thermolysis of 3,6-diphenyl-2-trityl- 3,6-dihydro-2H-1,2-oxazine (Compound 6) under air at 0.5L/min, 15 wt% in hyper crosslinked polymer (HCP-1-OEt) as the supporting matrix, under PID feedback control. The target NO concentration is set at 2 ppm; (FIG.16C) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2- oxazine (Compound 6) under air at 0.5L/min, 15 wt% in alumina as the supporting matrix, at 150^oC; (FIG.16D) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6) under air at 0.5L/min, 15 wt% in UIO-67 as the supporting matrix, at 150^oC; (FIG.16E) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6) under air at 0.5L/min, 15 wt% in PAF-1 as the supporting matrix, at 150^oC; (FIG.16F) thermolysis of 3,6-diphenyl-2-trityl-3,6- dihydro-2H-1,2-oxazine (Compound 6) under air at 0.5L/min, 15 wt% in crosslinked polystyrene as the supporting matrix, at 150^oC; and (FIG.16G) thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro- 2H-1,2-oxazine (Compound 6) under air at 0.5L/min, 15 wt% in linear polystyrene as the supporting matrix, at 150^oC. Compared to FIG.16F, dense polymer supporting matrix results in spikes on the NO curve and lower NO yield. [0030] FIG.17 is a graph showing thermolysis of 3,6-diphenyl-2-trityl-3,6-dihydro-2H-1,2-oxazine (Compound 6) under 100% Oxygen at 0.5L/min, 15 wt% in HCP-1-OEt as the supporting matrix, at 150^oC. [0031] FIG.18 is a schematic showing an apparatus of a portable inhalation device 1802, with an NO generator (1) including a heating element (2) and NO releasing materials (3), a power control circuit (4), a battery (5), an airway flowmeter (6), an NO sensor (7), an NO2 sensor (8), and a signal circuit board (9). DETAILED DESCRIPTION [0032] Inhaled nitric oxide (iNO) can be used to treat a variety of pulmonary disorders such as pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, and asthma among others. However, current iNO therapy requires a complex and expensive system of gaseous NO storage cylinders and devices to monitor and regulate the dilution and delivery of NO, limiting the availability of iNO treatment. Ideally, iNO delivery systems would be inexpensive, portable, and result in pure, controlled, and sustained levels of NO in a mixture of air or oxygen. [0033] The development of portable NO generation and delivery that provides pure, controlled, and sustained levels of NO in a mixture of air or oxygen faces numerous challenges. Current methods are designed for in vivo release under conditions close to ambient temperatures. This results in limited stability and a short shelf-life. Another challenge includes maintaining purity of generated NO as NO is highly reactive, spontaneously forming NO₂ in the presence of O_2. [0034] NO has been successfully produced via ionization of air under the action of a corona discharge via iridium spark plugs. However, the produced gas stream is heavily contaminated with metal nanoparticles and ozone and the system requires large amounts of power to generate the gas stream. While contaminants can be filtered before inhalation, the lifetime of a filter is not unlimited, and it is unclear how one can tell when a filter is depleted. Moreover, such systems generally have high power demands, further decreasing their useability. NO can also be formed via chemical or electrochemical reduction of higher NOx, typically nitrite or NO₂. This approach is limited by the complicated kinetics, must be subject to careful feedback control, has dangerous NO precursors, and has a minor explosion hazard. NO also has been generated via photolysis of nitrosothiols, but nitrosothiols have limited stability at room temperature. Furthermore, this approach is not currently compatible with release under air as substantial NO2 is observed. [0035] The current disclosure provides thermo-responsive NO releasing compounds and delivery systems that are highly portable and can be stored for extended periods with no or limited loss of NO delivery activity. In particular embodiments, the current disclosure provides thermally induced NO release from a porous matrix. In some aspects, the compositions may be amorphous solid dispersions including NO donors and porous matrices. In some aspects, the current disclosure provides an administration device for heating NO releasing materials and delivering the released NO to a patient for inhalation. [0036] In the disclosed systems and methods, hydroxylamine derivatives are thought to be converted to labile nitrosos via retro-cycloadditions (Class 1) and retro-ene (Class 2) reactions (FIG.2). From the in-situ generated nitroso, NO is quickly released through C-N homolysis. These novel NO-releasing compounds have more tunable release profiles relative to conventional donors such as S-nitrosothiols because the kinetics can be controlled by more than bond homolysis. For example, the release profile may also be controlled by heat. [0037] The disclosed compounds release NO at high temperatures. Class 1 and 2 donors release NO in modest and high yields (5-95%) at temperatures between 80°C and 190°C, including 85°C, 90°C, 95°C, 100°C, 110°C, 115°C, 120°Cm 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C, 165°C, 170°C, 175°C, 180°C, 185°C, 190°C, or any fraction thereof. For example, NO release may be obtained by applying heat at 150ºC to hydroxylamine derivatives as shown in FIGs.4A or 6B, at 100 ºC as shown in FIG.4B, at 190 ºC as shown in FIG.4C, at 90 ºC as shown in FIGs.8B and 9B, at 120 ºC as shown in FIG.11A and the like. While the compounds may be delivered via a variety of devices, in some aspects, the compounds are incorporated into a porous matrix as shown in FIG.1 and released on the application of heat. The use of such compositions may also reduce NO₂ contamination as shown in FIG.16A. In other aspects, the porous matrix compounds including the hydroxylamine derivatives may be heated using an inhalation device as described in further detail with reference to FIG.18. [0038] The disclosed NO donors are also stable under ambient conditions for at least eleven weeks without refrigeration when dispersed in a hyper-crosslinked polymer (HCP-1) (FIG.6C). The yield of NO per release trial drops from 65% to 50% at 80 days of storage on the bench. For comparison, FIG.10A shows that one of the most common chemical sources of NO, S-nitroso- N-acetylpenicillamine, lose 70% of their activity after just three weeks under identical conditions when dispersed in a hyper-crosslinked polymer (HCP-1). [0039] Aspects of the current disclosure are now described with additional detail and options as follows: (i) Hydroxylamine NO Donors; (ii) Porous Matrices & Associated Considerations; (iii) Application of Heat; (iv) Purity; (v) Stability; (vi) Administration; (vii) Disorders for Treatment; (viii) Exemplary Embodiments; (ix) Experimental Examples; and (x) Closing Paragraphs. These headings are provided for organizational purposes only and do not limit the scope or interpretation of the disclosure. [0040] (i) Hydroxylamine NO Donors. The terms “nitric oxide donor” or “NO donor” refer broadly to species and/or compounds that donate, release and/or directly or indirectly transfer a nitric oxide species, and/or stimulate the endogenous production of nitric oxide in vivo and/or elevate endogenous levels of nitric oxide in vivo, such that the biological activity of the nitric oxide species is expressed at the intended site of action. [0041] The terms “nitric oxide releasing” or “nitric oxide donating” refer to species that donate, release and/or directly or indirectly transfer any one (or two or more) of the three redox forms of nitrogen monoxide (NO+, NO−, NO (e.g., •NO)) and/or methods of donating, releasing and/or directly or indirectly transferring any one (or two or more) of the three redox forms of nitrogen monoxide (NO+, NO−, NO). In some embodiments, the nitric oxide release is accomplished such that the biological activity of the nitrogen monoxide species is expressed at the intended site of action. [0042] NO donor compounds disclosed herein are thermo-responsive, meaning that they release NO upon the application of heat. In some aspects, the donors may be designed to form unstable nitrosos from the hydroxylamine oxidation state organic molecules when heated. The NO release mechanism of dihydro oxazine compositions of Formula I, N-allyl compositions of Formula II, and O-allyl compositions of Formula III show nitroso release allowing hydroxylamine derived NO, with moisture stable motifs, and tunable release temperatures. Because the substituents represented by R₁-R₇ do not directly participate in release of NO, a variety of substituents are expected to be viable NO releasing molecules. [0043] In embodiments, NO donors may include compounds of Formula I, II, and III. R₅ R₆ [0044] R₁ in Formulas I, II, and III includes an atom bound to N wherein a weak bond is formed. Without being bound by theory, compounds of Formula I are believed to form a transient nitroso (NO-R₁) via a retro-cycloaddition, more specifically, a retro 4+2 cycloaddition, reaction as shown in FIG.2. Without being bound by theory, compounds of Formula II and III are believed to form a transient nitroso (NO-R₁) via a retro ene reaction, reactions II and III in FIG.2. The bolded bonds and atoms effect the desired reactivity, and the formation of the nitroso. [0045] In reactions I, II, and III, all three donors of Formulas I, II, and III, are thought to converge to the same intermediate, a nitroso bound to substituent R₁. Once this nitroso is generated, homolysis of the NO-R₁ bond furnishes NO. The structural requirements for this step are only that the NO-R₁ bond is sufficiently weak to spontaneously break at the reaction temperature, for example, between 45ºC - 300ºC. Nitrosos form notoriously weak bonds to other atoms. Therefore, there are many identities of R₁ where this could be the case. In some aspects, R1 may be hydrogen, C_1-20-alkyl, C_3-8-cycloalkyl, wherein in each C_1-20-alkyl-, C_3-8-cycloalkyl-, one CH₂ group may optionally be replaced by CO, SO or SO₂, SO3, SiR^N2 one CH₂ group optionally by O or NR^N and one H group optionally by C1-C20 aryl, heteroaryl, or alkyl groups, halogens, OR, or NR^N, where superscript N is a whole number. R1 may also be a hydrocarbon polymer. In some aspects, R₁ may include organic compounds. In embodiments, R₁ includes alkyls and cycloalkyls including reactive non-metals such as H, C, N, O, P, S, and Se. [0046] In embodiments, R2-R7 may be a wide range of chemical motifs as they do not directly participate in bond forming and breaking reactions resulting in the release of NO. For example, R2, R3, R4, R5, R6, and R7 of Formula I and R2, R3, R4, R5, and R6 of Formulas II and III may independently include an organic molecule. For example, R2, R3, R4, R5, R6, and R7 of Formula I and R2, R3, R4, R5, and R6 of Formulas II and III may independently be selected from an alkyl group, alcohol, aldehyde, a carboxylic acid, esters nitrile, an aromatic group, an ether, an amine, amide, silane, phosphine, thiol, thioether, or a halide. In embodiments, the organic molecule may be any organic molecule that does not prevent the release of NO from the thermo-responsive hydroxylamine NO releasing compounds. In some embodiments, R2 and R7 of Formula I may be the same. For example, R2 and R7 may include the same carbon and the compound of Formula I forms the bicyclic compound of Formula I.I. [0047] In some aspects, R2 and R7 of Formula I may be bound together. For example, R2 may include one carbon, R7 may include one carbon, and the carbon of R2 may be bound to the carbon of R7. In the case where R2 and R7 include only one carbon, the compound of Formula I forms the bicyclic compound of Formula I.II. R₅ R₂ and R₇ may independently include any number of carbon atoms and may be bound together at any atom of their structure. For example, R₂ and R₇ may bind together to form a 5 member bicyclic oxazine, 6 member bicyclic oxazine, or a 7 member bicyclic oxazine. [0049] Because R₂ to R₇ are not thought to directly participate in the formation of the nitroso, a wide variety of substitution patterns may be effective NO donors. [0050] In some aspects, R1 may include C, N, O, P, S with additional substituent groups as shown in the examples below: [0051] In embodiments, R₁ is a triphenyl methyl group, i.e. a trityl, of Formula IV. Formula IV [0052] The atom bound to N is the carbon of the methyl group, i.e. location *. R₈, R_9, and R₁₀ independently include an organic molecule or an inorganic molecule and, although shown in the para position, R₈, R_9, and R₁₀ can be ortho, meta or para with respect to the carbon bound to the central junction carbon (i.e. the sp³ carbon). In embodiments, R₈, R_9, and R₁₀ include Hydrogen (H), a t-butyl group, a phenyl group, or Bromide (Br). [0053] In embodiments, R₁ is a triphenyl methyl group, i.e. a trityl, of Formula V [0054] The atom bound to N is the carbon of the methyl group, i.e. location *. R8, R9, and R10 independently include an organic molecule or an inorganic molecule and, although shown in the para position, R8, R9, and R10 can be ortho, meta or para with respect to the carbon bound to the central junction carbon (i.e. the sp³ carbon). R11 can include a halogen or hydrogen and, although shown in the ortho position, can be in the ortho, meta, or para position with regard to the central junction. In embodiments, R8, R9, and R10 can include Hydrogen (H), a t-butyl group, a phenyl group, or Bromide (Br), a resin, or hydrogen, and R11 can include a halogen, such as chlorine, or hydrogen. [0055] For example, compounds of Formula IV may have the structures shown in Table 1, below. Table 1 Exemplary compounds of Formula IV [0056] For the general chemical formulas provided herein, if no substituent is indicated, a person of ordinary skill in the art will appreciate that the substituent is hydrogen. A bond that is not connected to an atom, but is shown, indicates that the position of such substituent is variable. A jagged line, wavy line, two wavy lines drawn through a bond or at the end of a bond indicates that some additional structure is bonded to that position. For a great number of the additional monomers disclosed herein, but not explicitly shown in structures it is understood by those in the art of polymers, that these monomers can be added to change the physical properties of resultant polymeric materials even where the elemental analysis would not indicate such a distinction could be expected. Such physical properties include solubility, charge, stability, cross-linking, secondary and tertiary structure, and the like. Moreover, if no stereochemistry is indicated for compounds having one or more chiral centers, all enantiomers and diastereomers are included. Where a number of substituents is not specified, there may be one or more substituents present. For reference FIG. 2 discloses the core molecular connectivity required to affect NO release through cycloreversion or retro-ene reactions. R2-R7 are spectator substituents. They may be a wide range of chemical motifs because they do not directly participate in bond forming and breaking reactions resulting in the release of NO. [0057] Organic molecules which may be used at R1 as well as R2, R3, R4, R5, R6, and R7 of Formula I and R2, R3, R4, R5, and R6 of Formulas II and III may be independently selected from molecules as described in: Clayden, et al. Organic Chemistry.2nd ed., Oxford University Press, 2012; Carey et al. Advanced Organic Chemistry, Part A: Structure and Mechanisms and Part B: Reactions and Synthesis. 5th ed., Springer, 2007, the disclosures of which are incorporated herein by reference. In embodiments, organic molecules may include single chain organic molecules, cyclic organic molecules, branched chain organic molecules, or may include multiple single chain, branched chain, and cyclic structures in combination. For example, organic molecules may include a methyl group, a dimethyl group, an ethyl group, a propyl group (n-propyl, iso-propyl), a butyl group (n-buyl, sec-butyl, iso-butyl, tert-butyl), a phenyl group, and a trityl group. In embodiments, organic molecules may include Hydrogen (H), Carbon (C), Nitrogen (N), Oxygen (O), Fluorine (F), Phosphorous (P), Sulfur (S), Chlorine (Cl), Selenium (Se), Bromine (Br), and Iodine (I). In some aspects, the organic molecules for use as R1-R7 can include an alkyl group, a carboxylic acid, esters nitrile, an aromatic group, an ether, an amine, silane, thiol/thioether, or a halide. For example, the organic molecule may be alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heterocyclyl, heteroalicyclyl, aralkyl, aryl(alkyl), cycloalkyl(alkyl),heteroaralkyl, heteroaryl(alkyl), heteroalicyclyl(alkyl), heterocyclyl(alkyl), hydroxy, alkoxy, acyl, cyano, O- carbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, O-carboxy, ester, C-carboxy, sulfenyl, sulfonyl, haloalkyl, haloalkoxy, mono-substituted amine, di-substituted amine, polyamino, allyl, diether, oxazine, or poly ether groups. [0058] In embodiments, the organic molecule may be any organic molecule that does not prevent the release of NO from the thermo-responsive hydroxylamine NO releasing compounds. [0059] In particular embodiments, organic molecules may include ethers, halogens, sulfides, sulfones, sulfoxides, phosphates, phosphonates, phosphites, silanes, silioxides, carboxylates, alcohols, alkenes, alkynes, arenes, and/or heterocycles. [0060] An “alkyl” as used herein refers to a fully saturated aliphatic hydrocarbon group. The alkyl moiety may be branched or straight chain. Examples of branched alkyl groups include iso-propyl, sec-butyl, t-butyl and the like. Examples of straight chain alkyl groups include methyl, ethyl, n- propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl and the like. The alkyl group may have 1 to 30 carbon atoms (whenever it appears herein, a numerical range such as “1 to 30” refers broadly to each integer in the given range; e.g., “1 to 6 or 1 to 12 carbon atoms” means that the alkyl group may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated). The “alkyl” group may also be a medium size alkyl having 1 to 12 carbon atoms. The “alkyl” group could also be a lower alkyl having 1 to 6 carbon atoms. An alkyl group may be substituted or unsubstituted. By way of example only, “C1-C5 alkyl” indicates that there are one to five carbon atoms in the alkyl chain, e.g., the alkyl chain is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert- butyl, pentyl (branched and straight-chained), etc. Typical alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl and hexyl. [0061] An “alkylene” as used herein refers broadly to a bivalent fully saturated straight chain aliphatic hydrocarbon group. Examples of alkylene groups include methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene and octylene. The alkylene group may have 1 to 30 carbon atoms (whenever it appears herein, a numerical range such as “1 to 30” refers broadly to each integer in the given range; e.g., “1 to 30 carbon atoms” means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 30 carbon atoms, although the present definition also covers the occurrence of the term “alkylene” where no numerical range is designated). The alkylene group may also be a medium size alkyl having 1 to 12 carbon atoms. The alkylene group could also be a lower alkyl having 1 to 6 carbon atoms. An alkylene group may be substituted or unsubstituted. For example, a lower alkylene group can be substituted by replacing one or more hydrogens of the lower alkylene group and/or by substituting both hydrogens on the same carbon with a C3-6 monocyclic cycloalkyl group [0062] An “alkenyl” as used herein refers broadly to a monovalent straight or branched chain radical of from two to twenty carbon atoms containing a carbon double bond(s) including 1- propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl and the like. An alkenyl group may be unsubstituted or substituted. [0063] An “alkynyl” as used herein refers broadly to a monovalent straight or branched chain radical of from two to twenty carbon atoms containing a carbon triple bond(s) including 1-propynyl, 1-butynyl, 2-butynyl and the like. An alkynyl group may be unsubstituted or substituted. [0064] A “cycloalkyl” as used herein refers broadly to a completely saturated (no double or triple bonds) mono- or multi- cyclic (such as bicyclic) hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro fashion. As used herein, the term “fused” refers broadly to two rings which have two atoms and one bond in common. As used herein, the term “bridged cycloalkyl” refers broadly to compounds wherein the cycloalkyl contains a linkage of one or more atoms connecting non-adjacent atoms. As used herein, the term “spiro” refers broadly to two rings which have one atom in common and the two rings are not linked by a bridge. Cycloalkyl groups can contain 3 to 30 atoms in the ring(s), 3 to 20 atoms in the ring(s), 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s) or 3 to 6 atoms in the ring(s). A cycloalkyl group may be unsubstituted or substituted. Examples of mono-cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Examples of fused cycloalkyl groups are decahydronaphthalenyl, dodecahydro- 1H-phenalenyl and tetradecahydroanthracenyl; examples of bridged cycloalkyl groups are bicyclo[1.1.1]pentyl, adamantanyl and norbornanyl; and examples of spiro cycloalkyl groups include spiro[3.3]heptane and spiro[4.5]decane. [0065] A “cycloalkenyl” as used herein refers broadly to a mono- or multi- cyclic (such as bicyclic) hydrocarbon ring system that contains one or more double bonds in at least one ring; although, if there is more than one, the double bonds cannot form a fully delocalized pi-electron system throughout all the rings (otherwise the group would be “aryl,” as defined herein). Cycloalkenyl groups can contain 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s) or 3 to 6 atoms in the ring(s). When composed of two or more rings, the rings may be connected together in a fused, bridged, or spiro fashion. A cycloalkenyl group may be unsubstituted or substituted. [0066] An “aryl” as used herein refers broadly to a carbocyclic (all carbon) monocyclic or multicyclic (such as bicyclic) aromatic ring system (including fused ring systems where two carbocyclic rings share a chemical bond) that has a fully delocalized pi-electron system throughout all the rings. The number of carbon atoms in an aryl group can vary. For example, the aryl group can be a C₆-C₁₄ aryl group, a C₆-C₁₀ aryl group or a C₆ aryl group. Examples of aryl groups include benzene, naphthalene and azulene. An aryl group may be substituted or unsubstituted. “heteroaryl” refers to a monocyclic or multicyclic (such as bicyclic) aromatic ring system (a ring system with fully delocalized pi-electron system) that contain(s) one or more heteroatoms (for example, 1, 2 or 3 heteroatoms), that is, an element other than carbon, including nitrogen, oxygen and sulfur. The number of atoms in the ring(s) of a heteroaryl group can vary. For example, the heteroaryl group can contain 4 to 14 atoms in the ring(s), 5 to 10 atoms in the ring(s) or 5 to 6 atoms in the ring(s), such as nine carbon atoms and one heteroatom; eight carbon atoms and two heteroatoms; seven carbon atoms and three heteroatoms; eight carbon atoms and one heteroatom; seven carbon atoms and two heteroatoms; six carbon atoms and three heteroatoms; five carbon atoms and four heteroatoms; five carbon atoms and one heteroatom; four carbon atoms and two heteroatoms; three carbon atoms and three heteroatoms; four carbon atoms and one heteroatom; three carbon atoms and two heteroatoms; or two carbon atoms and three heteroatoms. Furthermore, the term “heteroaryl” includes fused ring systems where two rings, such as at least one aryl ring and at least one heteroaryl ring or at least two heteroaryl rings, share at least one chemical bond. Examples of heteroaryl rings include furan, thiophene, benzothiophene, oxazole, benzoxazole, 1,2,3-oxadiazole, benzothiazole, imidazole, benzimidazole, indole, indazole, pyrazole, benzopyrazole, isoxazole, benzoisoxazole, isothiazole, thiadiazole, pyridine, pyridazine, pyrazine, quinoline, and isoquinoline. A heteroaryl group may be substituted or unsubstituted. [0067] A “heterocyclyl” or “heteroalicyclyl” as used herein refers broadly to three-, four-, five-, six- , seven-, eight-, up to 18-membered monocyclic, bicyclic and tricyclic ring system wherein carbon atoms together with from 1 to 5 heteroatoms constitute said ring system. A heterocycle may optionally contain one or more unsaturated bonds situated in such a way, however, that a fully delocalized pi-electron system does not occur throughout all the rings. The heteroatom(s) is an element other than carbon including oxygen, sulfur and nitrogen. A heterocycle may further contain one or more carbonyl or thiocarbonyl functionalities, so as to make the definition include oxo-systems and thio-systems such as lactams, lactones, cyclic imides, cyclic thioimides and cyclic carbamates. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro fashion. As used herein, the term “fused” refers to two rings which have two atoms and one bond in common. As used herein, the term “bridged heterocyclyl” or “bridged heteroalicyclyl” refers to compounds wherein the heterocyclyl or heteroalicyclyl contains a linkage of one or more atoms connecting non-adjacent atoms. As used herein, the term “spiro” refers to two rings which have one atom in common and the two rings are not linked by a bridge. Heterocyclyl and heteroalicyclyl groups can contain 3 to 30 atoms in the ring(s), 3 to 20 atoms in the ring(s), 3 to 10 atoms in the ring(s), 3 to 8 atoms in the ring(s) or 3 to 6 atoms in the ring(s). For example, five carbon atoms and one heteroatom; four carbon atoms and two heteroatoms; three carbon atoms and three heteroatoms; four carbon atoms and one heteroatom; three carbon atoms and two heteroatoms; two carbon atoms and three heteroatoms; one carbon atom and four heteroatoms; three carbon atoms and one heteroatom; or two carbon atoms and one heteroatom. Additionally, any nitrogens in a heteroalicyclic may be quaternized. Heterocyclyl or heteroalicyclic groups may be unsubstituted or substituted. Examples of such “heterocyclyl” or “heteroalicyclyl” groups include 1,3-dioxin, 1,3-dioxane, 1,4-dioxane, 1,2-dioxolane, 1,3-dioxolane, 1,4-dioxolane, 1,3-oxathiane, 1,4-oxathiin, maleimide, succinimide, acid, dioxopiperazine, imidazoline, imidazolidine, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, morpholine, oxirane, piperidine, piperazine, pyrrolidine, azepane, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran, thiamorpholine, thiamorpholine sulfoxide, thiamorpholine sulfone and their benzo-fused analogs (e.g., benzimidazolidinone, tetrahydroquinoline and/or 3,4-methylenedioxyphenyl). [0068] An “aralkyl” and “aryl(alkyl)” as used herein refers refers broadly to an aryl group connected, as a substituent, via a lower alkylene group. The lower alkylene and aryl group of an aralkyl may be substituted or unsubstituted. Examples include benzyl, 2-phenylalkyl, 3- phenylalkyl and naphthylalkyl. [0069] A “cycloalkyl(alkyl)” as used herein refers broadly to a cycloalkyl group connected, as a substituent, via a lower alkylene group. The lower alkylene and cycloalkyl group of a cycloalkyl(alkyl) may be substituted or unsubstituted. [0070] A “heteroaralkyl” and “heteroaryl(alkyl)” as used herein refers broadly to a heteroaryl group connected, as a substituent, via a lower alkylene group. The lower alkylene and heteroaryl group of heteroaralkyl may be substituted or unsubstituted. Examples include 2-thienylalkyl, 3- thienylalkyl, furylalkyl, thienylalkyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl and imidazolylalkyl and their benzo-fused analogs. [0071] A “heteroalicyclyl(alkyl)” and “heterocyclyl(alkyl)” as used herein refers broadly to a heterocyclic or a heteroalicyclic group connected, as a substituent, via a lower alkylene group. The lower alkylene and heterocyclyl of a (heteroalicyclyl)alkyl may be substituted or unsubstituted. Examples include tetrahydro-2H-pyran-4-yl(methyl), piperidin-4-yl(ethyl), piperidin-4-yl(propyl), tetrahydro-2H-thiopyran-4-yl(methyl) and 1,3-thiazinan-4-yl(methyl). [0072] An “hydroxy” as used herein refers to an –OH group. [0073] An “alkoxy” as used herein refers broadly to the Formula –OR wherein R is an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl) is defined herein. Examples of alkoxys are methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, tert- butoxy, phenoxy and benzoxy. An alkoxy may be substituted or unsubstituted. [0074] An “acyl” as used herein refers broadly to a hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl) and heterocyclyl(alkyl) connected, as substituents, via a carbonyl group. Examples include formyl, acetyl, propanoyl, benzoyl and acryl. An acyl may be substituted or unsubstituted. [0075] A “cyano” group as used herein refers to a “-CN” group. [0076] A “halogen atom” or “halogen” as used herein refers to any one of the radio-stable atoms of column 7 of the Periodic Table of the Elements, such as, fluorine, chlorine, bromine and iodine. [0077] An “O-carbamyl” group as used herein refers to a “-OC(=O)N(R_AR_B)” group in which R_A and R_B can be independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl). An O-carbamyl may be substituted or unsubstituted. [0078] An “N-carbamyl” group as used herein refers broadly to an “ROC(=O)N(RA)-” group in which R and RA can be independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl). An N-carbamyl may be substituted or unsubstituted. [0079] A “C-amido” group as used herein refers broadly to a “-C(=O)N(RARB)” group in which RA and RB can be independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl). A C-amido may be substituted or unsubstituted. [0080] An “N-amido” group as used herein refers broadly to a “RC(=O)N(RA)-” group in which R and RA can be independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl). An N-amido may be substituted or unsubstituted. [0081] A “S-sulfonamido” group as used herein refers broadly to a “-SO2N(RARB)” group in which RA and RB can be independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl). An S-sulfonamido may be substituted or unsubstituted. [0082] A “N-sulfonamido” group as used herein refers to a “RSO2N(RA)-” group in which R and RA can be independently hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl). An N-sulfonamido may be substituted or unsubstituted. [0083] An “O-carboxy” group as used herein refers to a “RC(=O)O-” group in which R can be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl), as defined herein. An O-carboxy may be substituted or unsubstituted. [0084] An “ester” and “C-carboxy” as used herein refers to a “-C(=O)OR” group in which R can be the same as defined with respect to O-carboxy. An ester and C-carboxy may be substituted or unsubstituted. [0085] A “sulfenyl” group as used herein refers to an “-SR” group in which R can be hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl). A sulfenyl may be substituted or unsubstituted. [0086] A “sulfonyl” group as used herein refers broadly to an “SO₂R” group in which R can be the same as defined with respect to sulfenyl. A sulfonyl may be substituted or unsubstituted. [0087] A “haloalkyl” as used herein refers to an alkyl group in which one or more of the hydrogen atoms are replaced by a halogen (e.g., mono-haloalkyl, di-haloalkyl, tri-haloalkyl and polyhaloalkyl). Such groups include chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1- chloro-2-fluoromethyl, 2-fluoroisobutyl and pentafluoroethyl. A haloalkyl may be substituted or unsubstituted. [0088] A “haloalkoxy” as used herein refers to an alkoxy group in which one or more of the hydrogen atoms are replaced by a halogen (e.g., mono-haloalkoxy, di-haloalkoxy and tri- haloalkoxy). Such groups include chloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-chloro-2-fluoromethoxy and 2-fluoroisobutoxy. A haloalkoxy may be substituted or unsubstituted. [0089] A hydroxylamine as used herein refers to inorganic compounds with the chemical formula NH2OH. [0090] A “mono-substituted amine” group as used herein refers broadly to a “-NHRA” group in which RA can be an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl), as defined herein. The RA may be substituted or unsubstituted. A mono-substituted amine group can include, for example, a mono-alkylamine group, a mono-C1-C6 alkylamine group, a mono-arylamine group, a mono-C6-C10 arylamine group and the like. Examples of mono-substituted amine groups include −NH(methyl), −NH(phenyl) and the like. [0091] A “di-substituted amine” group as used herein refers broadly to a “-NR_AR_B” group in which R_A and R_B can be independently an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl), as defined herein. R_A and R_B can independently be substituted or unsubstituted. A di-substituted amine group can include, for example, a di-alkylamine group, a di-C₁-C₆ alkylamine group, a di- arylamine group, a di-C₆-C₁₀ arylamine group and the like. Examples of di-substituted amine groups include −N(methyl)2, −N(phenyl)(methyl), −N(ethyl)(methyl) and the like. As used herein, “mono-substituted amine(alkyl)” group refers broadly to a mono-substituted amine as provided herein connected, as a substituent, via a lower alkylene group. A mono-substituted amine(alkyl) may be substituted or unsubstituted. A mono-substituted amine(alkyl) group can include, for example, a mono-alkylamine(alkyl) group, a mono-C₁-C₆ alkylamine(C₁-C₆ alkyl) group, a mono- arylamine(alkyl group), a mono-C6-C10 arylamine(C1-C6 alkyl) group and the like. Examples of mono-substituted amine(alkyl) groups include −CH₂NH(methyl), −CH₂NH(phenyl), −CH₂CH₂NH(methyl), −CH₂CH₂NH(phenyl) and the like. [0092] A “polyamino” as used herein refers broadly to “-(N(RA)RB-)n-N(RC)( R`)”. For illustration, the term polyamino can include -N(RA)alkyl-N(RA)alkyl-N(RA)alkyl-N(RA)alkyl-H. In some embodiments, the alkyl of the polyamino is as disclosed elsewhere herein. While this example has only 4 repeat units, the term “polyamino” may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 repeat units. RA, RC, and RD can be independently a hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl), as defined herein, and wherein RB connects the two “N” groups and can be (independently of RA, RC, and RD) a substituted or unsubstituted alkylene group. RA, RC, and RD can independently further be substituted or unsubstituted. As noted here, the polyamino includes amine groups with intervening alkyl groups. [0093] Organic molecules can include an allyl group referring to a substituent with the structural formula −CH2−HC=CH2. It includes a methylene bridge (−CH2−) attached to a vinyl group (−CH=CH2). [0094] A “diether-” as used herein refers to an “-ORBO-RA” group in which RA can be a hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl), as defined herein, and wherein RB connects the two “O” groups and can be a substituted or unsubstituted alkylene group. RA can independently further be substituted or unsubstituted. [0095] A “polyether” as used herein refers to a repeating –(ORB-)nORA group. For illustration, the term polyether can include -Oalkyl-Oalkyl-Oalkyl-Oalkyl-ORA. In some embodiments, the alkyl of the polyether is as disclosed elsewhere herein. While this example has only 4 repeat units, the term “polyether” may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 repeat units. R_A can be a hydrogen, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, a cycloalkenyl, aryl, heteroaryl, heterocyclyl, cycloalkyl(alkyl), aryl(alkyl), heteroaryl(alkyl) or heterocyclyl(alkyl), as defined herein. R_B can be a substituted or unsubstituted alkylene group. R_A can independently further be substituted or unsubstituted. As noted here, the polyether includes ether groups with intervening alkyl groups (where alkyl is as defined elsewhere herein and can be optionally substituted). [0096] Oxazines as used herein refer to heterocyclic organic compounds containing one oxygen and one nitrogen atom in a cyclohexa-1,4-diene ring. Isomers exist depending on the relative position of the heteroatoms and relative position of the double bonds. Reference to “oxazines” herein should be interpreted to refer to dihydro oxazines. The shorthand “oxazine” phrasing is used in places herein rather than “dihydro oxazines” for consistency with its common use in chemical literature. [0097] Where the number of substituents is not specified (e.g. haloalkyl), there may be one or more substituents present. For example, “haloalkyl” may include one or more of the same or different halogens. As another example, “C1-C3 alkoxyphenyl” may include one or more of the same or different alkoxy groups containing one, two or three atoms. [0098] (ii) Porous Matrices & Associated Considerations. In particular embodiments, porous matrices are formed from polymers, lipids, or resins. In particular embodiments, the polymers form amorphous solid dispersions, a form typically associated with, in-vivo applications such as drug release, but used in an ex-vivo application here. [0099] Amorphous solid dispersions (ASD) are functionally a polymeric “solvent” for a molecule of interest. Molecules in ASDs are not arranged in the periodic array as they are in solid crystalline phases. They are as amorphous and disordered as a molecule in solvent is. This is advantageous within the context of the current disclosure over true solvent due to having essentially no vapor pressure at any temperature (volatile organic solvent is not best for patients to inhale). Exemplary matrices are non-polar and/or porous. In some aspects, the compounds of Formula I, II, or III can be covalently or ionically bonded to the matrix itself (as opposed to non-covalently dispersed). In particular embodiments, the pore sizes of matrices disclosed herein are 0.5 nm – 15 nm, 0.5 nm to 1 nm, 1 nm-10 nm, or most preferably 1 nm-5 nm. In some aspects, the compounds of Formula I, II, or III can be non-covalently dispersed. [0100] Matrices that fit this description can be characterized as permanently micro or mesoporous neutral organic polymers. Their general composition is of rigid organic motifs of moderate to low polarity connected in such a way as to form structural voids on the domain of 0.5-5nm. They are generally highly interconnected network polymers. They therefore do not have a well-defined molecular weight. This high molecular weight renders them insoluble in nearly all solvent. Their morphology is generally nanoparticulate (50nm-10 uM). [0101] Representative matrices are: (i) cross-linked polystyrene matrices (Reactive & Functional Polymers, 2006, 66, 768–779, doi.org/10.1016/j.reactfunctpolym.2005.11.004 and Nanotechnol Russia, 2009, 4, 665–675, doi.org/10.1134/S1995078009090109; (ii) hyper-crosslinked polymers (J. Mater. Chem. A, 2016, 4, 10110-10113, pubs.rsc.org/en/content/articlelanding/2016/ta/c6ta03257e; Angew. Chem. Int. Ed. 2008, 47, 3450–3453, onlinelibrary.wiley.com/doi/10.1002/anie.200705710); pubs.rsc.org/en/content/articlepdf/2018/cc/c8cc03951h (iii) porous aromatic frameworks (ACS Cent. Sci. 2019, 5, 409−418, pubs.acs.org/doi/10.1021/acscentsci.9b00047; Energy Environ. Sci., 2011,4, 3991-3999, pubs.rsc.org/en/content/articlelanding/2011/ee/c1ee01222c); (iv) porous organic polymers (Chem. Soc. Rev., 2017, 46, 3134, pubs.rsc.org/en/content/articlelanding/2017/cs/c7cs00033b; Chem. Rev.2020, 120, 1438−1511, pubs.acs.org/doi/10.1021/acs.chemrev.9b00223); (v) conjugated microporous polymers (Chem. Rev. 2020, 120, 4, 2171–2214, pubs.acs.org/doi/10.1021/acs.chemrev.9b00399; Chem. Soc. Rev., 2013,42, 8012-8031, pubs.rsc.org/en/content/articlelanding/2013/cs/c3cs60160a); (vi) covalent organic frameworks (Adv. Funct. Mater. 2018, 28, 1705553, onlinelibrary.wiley.com/doi/full/10.1002/adfm.201705553; Chem. Soc. Rev., 2012, 41, 6010– 6022, pubs.rsc.org/en/content/articlelanding/2012/cs/c2cs35157a); and (vii) Polymers of intrinsic microporosity Polymer, 2020, 202, 122736, doi.org/10.1016/j.polymer.2020.122736; Polymer Reviews, 2023, 64(1), 251–305, doi.org/10.1080/15583724.2023.2236677). [0102] Additional types of material can be used as porous matrices within the context of the current disclosure. For example, neutrally charged polymers that can be used as coating within embodiments of the disclosure include polyethylene glycol (PEG); poly(propylene glycol); and polyalkylene oxide copolymers, (PLURONIC®, BASF Corp., Mount Olive, NJ). Neutrally charged polymers also include zwitterionic polymers. Zwitterionic refers to the property of overall charge neutrality while having both a positive and a negative electrical charge. Zwitterionic polymers can behave like regions of cell membranes that resist cell and protein adhesion. [0103] Zwitterionic polymers include zwitterionic constitutional units including pendant groups (i.e., groups pendant from the polymer backbone) with zwitterionic groups. Exemplary zwitterionic pendant groups include carboxybetaine groups (e.g., -Ra-N+(Rb)(Rc)-Rd-CO2-, where Ra is a linker group that covalently couples the polymer backbone to the cationic nitrogen center of the carboxybetaine groups, Rb and Rc are nitrogen substituents, and Rd is a linker group that covalently couples the cationic nitrogen center to the carboxy group of the carboxybetaine group). [0104] Examples of negatively charged polymers include alginic acids; carboxylic acid polysaccharides; carboxymethyl cellulose; carboxymethyl cellulose-cysteine; carrageenan (e.g., Gelcarin® 209, Gelcarin® 379); chondroitin sulfate; glycosaminoglycans; mucopolysaccharides; negatively charged polysaccharides (e.g., dextran sulfate); poly(acrylic acid); poly(D-aspartic acid); poly(L-aspartic acid); poly(L-aspartic acid) sodium salt; poly(D-glutamic acid); poly(L- glutamic acid); poly(L-glutamic acid) sodium salt; poly(methacrylic acid); sodium alginate (e.g., Protanal® LF 120M, Protanal® LF 200M, Protanal® LF 200D); sodium carboxymethyl cellulose (CMC); sulfated polysaccharides (heparins, agaropectins); pectin, gelatin and hyaluronic acid. [0105] In particular embodiments, polymers can include "star shaped polymers," which refer to branched polymers in which two or more polymer branches extend from a core. The core is a group of atoms having two or more functional groups from which the branches can be extended by polymerization. [0106] In particular embodiments, the branches are zwitterionic or negatively-charged polymeric branches. For star polymers, the branch precursors can be converted to zwitterionic or negatively- charged polymers via hydrolysis, ultraviolet irradiation, or heat. The polymers also may be obtained by any polymerization method effective for polymerization of unsaturated monomers, including atom transfer radical polymerization (ATRP), reversible addition−fragmentation chain transfer polymerization (RAFT), photo-polymerization, ring-opening polymerization (ROP), condensation, Michael addition, branch generation/propagation reaction, or other reactions. [0107] Exemplary resins where the donor can be attached include trityl chloride resin (trityl-Cl, Novabiochem, P/N 01-64-0074), 2-Chlorotrityl chloride resin (Novabiochem, P/N 01-64-0021), DHPP (Bachem, P/N Q-1755), MBHA (Applied Biosystems P/N 400377), 4-methyltrityl chloride resin (Novabiochem, P/N 01-64-0075), 4-methoxytrityl chloride resin (Novabiochem, P/N 01-64- 0076), Hydroxy-(2-chorophnyl)methyl-PS (Novabiochem, P/N 01-64-0345), Rink Acid Resin (Novabiochem P/Ns 01-64-0380, 01-64-0202), NovaSyn TGT alcohol resin (Novabiochem, P/N 01-64-0074), Wang resin, and hydroxymethyl phenoxymethyl polystyrene (HMP) resin, TAF-OH (Chem. Commun.2018, 54, 9321). [0108] Blends of polymers, lipids, and/or resins in any concentration and in any ratio can also be used. Blending different polymer types in different ratios using various grades can result in characteristics that borrow from each of the contributing polymers. Various terminal group chemistries can also be adopted. [0109] A variety of surface stabilizers may also be used to prevent the particles from clumping or aggregating. Representative surface stabilizers include gelatin, lecithin, dextran, gum acacia, cholesterol, tragacanth, stearic acid, benzalkonium chloride, calcium stearate, glycerol monostearate, cetostearyl alcohol, cetomacrogol emulsifying wax, sorbitan esters, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyethylene glycols, polyoxyethylene stearates, colloidal silicon dioxide, phosphates, sodium dodecylsulfate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl- cellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, triethanolamine, polyvinyl alcohol, polyvinylpyrrolidone, tyloxapol, poloxamers, poloxamines, poloxamine 908, dialkylesters of sodium sulfosuccinic acid, sodium lauryl sulfate, an alkyl aryl polyether sulfonate, a mixture of sucrose stearate and sucrose distearate, p-isononylphenoxypoly-(glycidol), SA9OHCO, decanoyl-N-methylglucamide, n-decyl-D-glucopyranoside, n-decyl-D- maltopyranoside, n-dodecyl-D-glucopyranoside, n-dodecyl-D-maltoside, heptanoyl-N- methylglucamide, n-heptyl-D-glucopyranoside, n-heptyl-D-thioglucoside, n-hexyl-D- glucopyranoside, nonanoyl-N-methylglucamide, n-nonyl-D-glucopyranoside, octanoyl-N- methylglucamide, n-octyl-D-glucopyranoside, and octyl-D thioglucopyranoside. Lysozymes can also be used as surface stabilizers for nanoparticulate compositions. [0110] Representative rate controlling polymers into which the particles can be formulated include chitosan, polyethylene oxide (PEO), polyvinyl acetate phthalate, gum arabic, agar, guar gum, cereal gums, dextran, casein, gelatin, pectin, carrageenan, waxes, shellac, hydrogenated vegetable oils, polyvinylpyrrolidone, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methylcelluose (HPMC), sodium carboxymethylcellulose (CMC), poly(ethylene) oxide, alkyl cellulose, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydrophilic cellulose derivatives, polyethylene glycol, polyvinylpyrrolidone, cellulose acetate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose acetate trimellitate, polyvinyl acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, polyvinyl acetaldiethylamino acetate, poly(alkylmethacrylate), poly(vinyl acetate), polymers derived from acrylic or methacrylic acid and their respective esters, and copolymers derived from acrylic or methacrylic acid and their respective esters. [0111] Methods of making particulate compositions are described, for example, in U.S. Pat. Nos. 5,518,187 and 5,862,999, both for "Method of Grinding Pharmaceutical Substances;" U.S. Pat. No.5,718,388, for "Continuous Method of Grinding Pharmaceutical Substances;" and U.S. Pat. No.5,510,118 for "Process of Preparing Therapeutic Compositions Containing Nanoparticles." [0112] In several embodiments, the combination of all the various components of the composition, including the concentrations, or other chemical features of the compounds, and other components in the compositions, contribute to the tunability of the properties of the compositions disclosed herein. In several embodiments, by changing one or more of these features, one or more properties of the compositions can be tuned according to preferred properties described herein. In several embodiments, the NO release rate, water solubility, degradation rate, viscosity, viscoelasticity, modulus, etc. are tunable. [0113] According to several embodiments, the NO donor can be formulated within a composition at a concentration equal to or at least 100 µg/mL, 1 mg/ml, 5 mg/ml, 10 mg/ml, 20 mg/ml, 25 mg/ml, 50 mg/ml, 75 mg/ml, 100 mg/ml or 200 mg/ml or higher. The amount of the polymer in the composition can be at least 0.1% by weight, based on the weight of the NO donor, and may be higher, e.g., at least 20% by weight, at least 30% by weight, or at least 50% by weight, same basis. In particular embodiments, any combinations of NO donors and polymers in an aqueous composition are selected to be mutually miscible. The NO donor and the polymer are considered mutually miscible if at least 90% of the polymeric components remain mutually soluble 24 hours after mixing and maintaining at room temperature in water at a concentration of each polymer of 1 mg/ml, upon visible examination. [0114] (iii) Application of Heat. NO is released from the NO donors following application of heat. Heat can be applied in a variety of ways, though most commonly will be applied through a heating element within a vaporization device. [0115] In particular embodiments, heat will be applied until a pre-determined temperature is reached. The predetermined temperature can be, for example, between 35ºC - 220ºC. In particular embodiments, the predetermined temperature can be between 45ºC - 210ºC. In particular embodiments, the predetermined temperature can be between 55ºC - 200ºC. In particular embodiments, the predetermined temperature can be between 65ºC - 200ºC. In particular embodiments, the predetermined temperature can be between 75ºC - 190ºC. In particular embodiments, the predetermined temperature can be between 85ºC - 180ºC. In particular embodiments, the predetermined temperature can be between 95ºC - 170ºC. In particular embodiments, the predetermined temperature can be between 105ºC - 160ºC. In particular embodiments, the predetermined temperature can be between 115ºC - 150ºC. In particular embodiments, the predetermined temperature can be between 125ºC - 140ºC. In particular embodiments, the predetermined temperature can be 100ºC, 101ºC, 102ºC, 103ºC, 104ºC, 105ºC, 106ºC, 107ºC, 108ºC, 109ºC, 110ºC, 111ºC, 112ºC, 113ºC, 114ºC, 115ºC, 116ºC, 117ºC, 118ºC, 119ºC, 120ºC, 121ºC, 122ºC, 123ºC, 124ºC, 125ºC, 126ºC, 127ºC, 128ºC, 129ºC, 130ºC, 131ºC, 132ºC, 133ºC, 134ºC, 135ºC, 136ºC, 137ºC, 138ºC, 139ºC, 140ºC, 141ºC, 142ºC, 143ºC, 144ºC, 145ºC, 146ºC, 147ºC, 148ºC, 149ºC, 150ºC, 151ºC, 152ºC, 153ºC, 154ºC, 155ºC, 156ºC, 157ºC, 158ºC, 159ºC, 160ºC, 161ºC, 162ºC, 163ºC, 164ºC, 165ºC, 166ºC, 167ºC, 168ºC, 169ºC, 170ºC, 171ºC, 172ºC, 173ºC, 174ºC, 175ºC, 176ºC, 177ºC, 178ºC, 179ºC, or 180ºC. [0116] (iv) Purity. NO release according to current disclosure is substantially pure or medical grade, meaning that NO₂ is not detected in a sample for inhalation by a subject at a level that outweighs the benefit of administration. In certain examples, NO₂ detection is below a predetermined threshold. In particular embodiments, any detected NO₂ must be less than 1000 parts per million (ppm), less than 900 ppm, less than 800 ppm, less than 700 ppm, less than 600 ppm, less than 500 ppm, less than 400 ppm, less than 300 ppm, less than 200 ppm, less than 100 ppm, or less than 50 ppm, or less than 1000 parts per billion (ppb), less than 900 ppb, less than 800 ppb, less than 700 ppb, less than 600 ppb, less than 500 ppb, less than 400 ppb, less than 300 ppb, less than 200 ppb, less than 100 ppb, or less than 100 ppb. In particular embodiments, NO2 is not detectable. Exemplary methods to detect NO2 are described elsewhere herein. [0117] (v) Stability. The term “stability,” and its equivalents can refer to how an amount, concentration, and/or quality of an NO donor varies with time under various conditions including environmental conditions. For example, a stability of an NO donor can be related to how much of the NO donor breaks down (e.g., by transforming into another chemical structure) and/or leaves (e.g., due to evaporation) a composition including the NO donor during storage. Various environmental conditions can impact the stability of an NO donor, such as any of temperature, humidity, electromagnetic radiation, the presence of stabilizers, and the like. [0118] The stability of an NO donor can be measured in a variety of ways. In some cases, the stability of an NO donor can be indicated by a percentage of the NO donor that remains after being stored under certain conditions and for a certain time period. In particular implementations, the stability of an NO donor can be a dimensionless number calculated by measuring an initial amount of the NO donor in a composition, measuring a final amount of the NO donor in the composition after the composition is stored for a period of time in one or more particular conditions, and mathematically dividing the final amount by the initial amount. [0119] “Stabilizer,” “stabilizing agent,” and their equivalents can refer to any substance in a composition that can increase the stability of an NO donor in the composition, as compared to the stability of the NO donor in a composition that lacks the stabilizer. In some cases, a stabilizer may chemically stabilize an NO donor in a composition. Porous matrices formed from polymers, lipids, and/or resins can act as stabilizing agents within the current disclosure. [0120] A “stable composition” can be defined in a variety of ways. In some examples, a stable composition retains a significant retained amount of an NO donor after being stored for a storage time and in one or more storage conditions. In some implementations, a significant retained amount of an NO donor can range from 0.2% to 100%. In some implementations, a significant retained amount of an NO donor can range from 0.9% to 90%. In some implementations, a significant retained amount of an NO donor can range from 5% to 80%. In some implementations, a significant retained amount of an NO donor can range from 15% to 80%. In some implementations, a significant retained amount of an NO donor can range from 25% to 70%. In some implementations, a significant retained amount of an NO donor can range from 35% to 60%. In particular implementations, a significant retained amount of an NO donor can include 30%, 35%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more. In some implementations, the storage time can range from 1 month, 5 weeks, 6, weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, or 11 weeks to 5 years or 3 months to 1 year. In particular implementations, a storage time can include 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more. In some implementations, the storage conditions can include a temperature ranging from 20°C to 60°C or 20°C to 30°C. In particular implementations, the storage conditions can include a temperature of 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, or more. In certain implementations, the storage conditions can include room temperature. The term “room temperature,” refers to a temperature in a range of 20-25°C. [0121] (vi) Administration. While the compounds disclosed herein may be administered using any means generally used, in some aspects, the delivery systems are configured to administer NO via inhalation. In particular embodiments, portable inhalers used with the current disclosure include vaporization devices. Vaporization devices include a heater element which vaporizes a pre-vapor formulation to produce a “vapor.” Such a vapor may be referred to herein as a “generated vapor.” A pre-vapor formulation can include a solid, and vaporization as described herein can include the transition of a substance from a solid phase to a gaseous, or gas-like phase. In embodiments, a pre-vapor or pre-sublimation formulation in accordance with the present disclosure includes any NO releasing molecule described herein. [0122] Vaporization devices (also known as vaping devices or e-vaping devices) include a power supply, such as a rechargeable battery, arranged in the device. The battery can be electrically connected to a heater, such that the heater heats to a temperature sufficient to convert a pre- vapor formulation to a vapor. The vapor exits the vaporization device through an outlet-end insert including at least one outlet. Conditions applied to the pre-vaporization or pre-sublimation substance may be modified to control the amount of NO released. For example, the amount or heat or the duration of the heat may be manually or automatically adjusted based on the characteristics of the pre-vaporization substance and the dose of NO to be released. In embodiments, an apparatus of the present disclosure can include a portable device, as shown in FIG.18, with an NO generator (1), a heating element (2), NO releasing materials (3), a power control circuit (4), a battery (5), an optional airway flowmeter (6), an NO sensor (7), an NO₂ sensor (8), and a signal circuit board (9). Such a device may be handheld, electronically controlled, and battery powered. In some aspects, such a device may be breath activated. [0123] As shown in FIG. 18, upon inhalation by the patient, of a carrier gas enters the device 1802 at a first end 1804 and travels through the device as shown by the arrow to exit at a second end 1806 for administration to the patient. The NO generator (1) includes a heating element (2) into or onto which NO releasing materials (3) are placed. In some aspects, the device 1802 is pre- loaded with NO releasing materials (3). In other aspects, cartridges or other distribution methods may be used to add the NO releasing materials (3) to the device 1802. The temperature of the heating element (2) may be fixed or variable depending on the use of the device. In some aspects, the temperature of the heating element (2) is controlled by the power control circuit (4) using power supplied by the battery (5). The rate of release of NO by the NO generator may be modified, at least in part, based on feedback from the airway flowmeter (6), heating element (2), a temperature sensor (not shown), the NO sensor (7) and the NO2 sensor (8). In embodiments, regulating the heat applied to the NO releasing molecule can regulate the release of the NO and therefor the flow rate of NO. The device 1802 may further included one or more printed circuit boards such as signal circuit board (9). The signal circuit board (9) may be operatively coupled to a temperature sensor (not shown) as well as the NO sensor (7) and the NO2 sensor (8) to regulate the amount and concentration of NO being released to the patient. [0124] (vii) Disorders for Treatment. [0125] The methods described herein can be used to treat, prevent, manage or lessen the severity of symptoms and infections associated with one or more pulmonary disorders or infections in a subject including a human through the administration of NO released from the NO donors described herein using one or more delivery systems including systems designed to administer dosages through inhalation. [0126] Representative pulmonary disorders include asthma, COPD, chronic bronchitis, emphysema, acute bronchitis (viral or bacterial). Lung diseases affecting the air sacs (alveoli) and/or interstitium include pneumonia, tuberculosis (caused by the bacteria Mycobacterium tuberculosis), emphysema, pulmonary edema, whether caused by COPD, heart failure, or direct injury to the lung, lung cancer, acute respiratory distress syndrome (ARDS), pneumoconiosis, interstitial lung disease (ILD), sarcoidosis, idiopathic pulmonary fibrosis, and autoimmune disease. [0127] Symptoms for these lung diseases include trouble breathing, shortness of breath, inability or decreased ability to exercise, coughing with or without blood or mucus, and pain when breathing in or out. For asthma, wheezing and chest tightness are common symptoms along with coughing and shortness of breath. COPD patients usually present with a chronic cough with large amounts of mucus production, as well as similar symptoms to that of asthma. Pulmonary fibrosis can produce a dry cough as well as fatigue, unexplained weight loss, and musculoskeletal pain. [0128] Patients suffering from these disorders can benefit from treatment with the compounds described herein. Because patients suffering from inflammatory respiratory disorders often have an underlying microbial infection, it can be useful to combine anti-inflammatory compounds with the NO-producing compounds to both treat the inflammatory lung disease and the respiratory infections. [0129] Examples of pulmonary infections that can be treated include bronchiectasis infection, pneumonia, valley fever, allergic bronchopulmonary aspergillosis (ABPA), ventilator acquired pneumonia, hospital acquired pneumonia, community acquired pneumonia, ventilator associated tracheobronchitis, lower respiratory tract infection, non-tuberculous Mycobacteria, anthrax, legionellosis, pertussis, bronchitis, Bronchiolitis, COPD-associated infection, and post-lung transplantation. [0130] Cystic fibrosis (CF) is a genetic disorder characterized by poor mucociliary clearance and chronic bacterial infections. NO has broad spectrum antibacterial activity against CF-relevant bacteria. [0131] In some aspects, the compounds described herein can penetrate and disrupt biofilms by reducing the bacterial biofilm, impairing growth of the bacterial biofilm, and/or preventing reformation of the bacterial biofilm. [0132] The methods described herein can lessen the severity of one or more of the following symptoms in a subject being treated: cough, wheezing, breathlessness, bronchiectasis, nasal polyps, hemoptysis, respiratory failure, and pulmonary exacerbation, among others. [0133] (viii) Exemplary Embodiments. [0134] First set of Exemplary Embodiments [0135] 1. A thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule. [0136] 2.The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 1, having the structure of Formula I, II, or III: R₅ R₆ wherein: R₁ is hydrogen, C, N, O, P, S, substituted or unsubstituted C_1-20-alkyl, or substituted or unsubstituted C_3-8-cycloalkyl, and R₂, R₃, R₄, R₅, R_6, and R₇ independently include Hydrogen (H), an alkyl group, alcohol, aldehyde, carboxylic acid, esters nitrile, an aromatic group, an ether, an amine, amide, phosphine, silane, thiol, thioether, or a halide, wherein in each C_1-20-alkyl-, C_3-8-cycloalkyl-, one CH₂ group may optionally be replaced by CO, SO or SO₂, SO3, SiR^N2, one CH₂ group optionally by O or NR^N , and one H group optionally by C₁-C₂₀ aryl, heteroaryl, or alkyl groups, halogens, OR, or NR^N. [0137] 3. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 1 or 2, wherein: the compound is Formula I; R₁, R₃, R₄, R₅, and R₆ are H; and R₂ and R₇ are a phenyl group. [0138] 4. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 1 or 2, wherein: R₁ is a triphenyl methyl group of Formula IV: carbon indicated by *, R₈, R_9, and R₁₀ include an organic molecule, and R8, R9, and R10 can be ortho, meta or para with respect to the carbon bound to the central junction carbon. [0139] 5. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 4, wherein: the compound is Formula I; R2 and R7 are a phenyl group; and R3, R4, R5, R6, R8, R9, and R10 are H. [0140] 6. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 4, wherein: the compound is Formula I; R2 includes one carbon, R7 includes one carbon, and the carbon of R2 is bound to the carbon of R7; and R3, R4, R5, R6, R8, R9 and R10 are H. [0141] 7. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 4, wherein: the compound is Formula II; R2, R3, R4, R5, and R6 are H; and R8, R9, and R10 are a phenyl group. [0142] 8. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-7, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 45 [0143] 9. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-8, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 100ºC. [0144] 10. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 9, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO within a temperature range of 45 ºC to 300ºC. [0145] 11. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-10, within a porous matrix. [0146] 12. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 11, wherein the porous matrix includes a polymer, lipid, or resin. [0147] 13. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 11 or 12, wherein the porous matrix includes an amorphous solid dispersion (ASD). [0148] 14. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 13, wherein the ASD includes a neutral organic polymer. [0149] 15. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 13 or 14, wherein the ASD includes a cross-linked polystyrene matrix, a hyper-crosslinked polymer, a porous aromatic framework, a porous organic polymer, a conjugated microporous polymer, and/or a covalent organic framework. [0150] 16. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 12, wherein the polymer includes PAF-1, PIM-1, or polystyrene. [0151] 17. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 12, wherein the resin includes trityl chloride resin, 2-Chlorotrityl chloride resin, DHPP, MBHA, 4- methyltrityl chloride resin, 4-methoxytrityl chloride resin, Hydroxy-(2-chorophnyl)methyl-PS, Rink Acid Resin, Wang resin, or hydroxymethyl phenoxymethyl polystyrene (HMP) resin. [0152] 18. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 12, wherein the resin includes trityl chloride resin. [0153] 19. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 11-18, wherein the porous matrix has a pore size of 0.5-1 nm. [0154] 20. A method of releasing nitric oxide (NO) from the hydroxylamine NO releasing molecule of any of embodiments 1-19, the method including applying heat to the hydroxylamine NO releasing molecule. [0155] 21. The method of embodiment 20, wherein the applying heat includes actuating a vaporization device including a heating element. [0156] 22. The method of embodiment 20 or 21, wherein the heat is applied so that the thermo- responsive hydroxylamine NO releasing molecule reaches a temperature of at least 45ºC. [0157] 23. The method of any of embodiments 20-22, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of at least 100ºC. [0158] 24. The method of any of embodiments 20-23, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of between 45ºC and 300ºC. [0159] 25. An inhaler including the hydroxylamine NO releasing molecule of any of embodiments 1-19. [0160] 26. The inhaler of embodiment 25, wherein the inhaler is a vaporization device. [0161] 27. A method including inhaling NO released from the hydroxylamine NO releasing molecule of any of embodiments 1-19. [0162] 28. The method of embodiment 27, wherein the method does not include inhaling NO2 with the NO. [0163] 29. A method of synthesizing trityl-diphenyloxazine including: combining trityl chloride of formula of formula of formula . [0164] 30. A method of synthesizing 2,5-diphenyloxazine including: combining (9H-fluoren-9-yl)methyl hydroxycarbamate of formula 1,3-butadiene of formula to form 2,5-diphenyloxazine of the formula . synthesizing trityl-bicyclicoxazine including: combining trityl chloride of formula and bicyclicoxazine of formula bicyclicoxazine of formula . thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments 1-19 in the treatment of pulmonary conditions. [0167] 33. The use of embodiment 32, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0168] 34. Use of the amorphous solid dispersion of any of embodiments 13-15 in the treatment of pulmonary conditions. [0169] 35. Use of the amorphous solid dispersion of embodiment 34, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0170] 36. An inhalation device for the delivery of inhaled NO from the thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments embodiment 1-19, the inhalation device including: a gas intake through which a carrier gas is introduced into the inhalation device; an outlet through which NO is released; an NO generator including a heating element positioned between the intake and the outlet; an NO sensor; and an NO₂ sensor, wherein feedback from the NO sensor and the NO₂ sensor regulates the amount of NO generated by the NO generator. [0171] 37. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Fomula I of Claim 2, wherein in each C1_-20-alkyl-, C_3-8-cycloalkyl-, one CH₂ group may optionally be replaced by CO, SO or SO2, SO3, SiR^N2. [0172] 38. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Fomula I of Claim 2, wherein one CH2 group may optionally be substituted by O or NR^N. [0173] 39. The thermos-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of Claim 2, wherein one H group may optionally be substituted by group optionally by C1-C20 aryl, heteroaryl, or alkyl groups, halogens, OR, or NR. [0174] Second set of Exemplary Embodiments [0175] 1. A thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule having the structure of Formula I, II, or III: R₅ Formula III, wherein R1 is selected from hydrogen, C, N, O, P, S, substituted or unsubstituted C1-20- alkyl, or substituted or unsubstituted C3-8-cycloalkyl; R2, R3, R4, R5, R6, and R7 include a phenyl group or hydrogen, and at least one of R2, R3, R4, R5, R6, and R7 is a phenyl group. [0176] 2. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 1 having the structure: , I; R1, R3, R4, R5, and R6 are H; and R2 and R7 are a phenyl group. [0177] 3. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 1, wherein R1 is a triphenyl methyl group of Formula IV: wherein the atom bound to N is the carbon indicated by *, R₈ and R₁₀ include a phenyl group or hydrogen, R₉ includes a phenyl group, a resin, or hydrogen, and R₁₁ includes chlorine or hydrogen and R8, R9, R10 and R11 can be ortho, meta or para with respect to the carbon bound to the central junction carbon. [0178] 4. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 3 having the structure: . hydroxylamine NO releasing molecule of any of embodiments 1-4, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 45ºC. [0180] 6. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-5, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 100ºC. [0181] 7. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-6, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO within a temperature range of 45 ºC to 300ºC. [0182] 8. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-7, within a porous matrix. [0183] 9. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 8, wherein the porous matrix includes a polymer, lipid, or resin. [0184] 10. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 8, wherein the porous matrix includes an amorphous solid dispersion (ASD). [0185] 11. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 10, wherein the ASD includes a neutral organic polymer. [0186] 12. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 10, wherein the ASD includes a cross-linked polystyrene matrix, a hyper-crosslinked polymer, a porous aromatic framework, a porous organic polymer, a conjugated microporous polymer, and/or a covalent organic framework. [0187] 13. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 9, wherein the polymer includes PAF-1, PIM-1, or polystyrene. [0188] 14. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 9, wherein the resin includes trityl chloride resin, 2-Chlorotrityl chloride resin, DHPP, MBHA, 4- methyltrityl chloride resin, 4-methoxytrityl chloride resin, Hydroxy-(2-chorophnyl)methyl-PS, Rink Acid Resin, Wang resin, or hydroxymethyl phenoxymethyl polystyrene (HMP) resin. [0189] 15. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 9, wherein the resin includes trityl chloride resin. [0190] 16. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 8, wherein the porous matrix has a pore size of 0.5nm-5 nm. [0191] 17. A method of releasing nitric oxide (NO) from the hydroxylamine NO releasing molecule of any of embodiments 1-16, the method including applying heat to the hydroxylamine NO releasing molecule. [0192] 18. The method of embodiment 17, wherein the applying heat includes actuating a vaporization device including a heating element. [0193] 19. The method of embodiment 17, wherein the heat is applied so that the thermo- responsive hydroxylamine NO releasing molecule reaches a temperature of at least 45ºC. [0194] 20. The method of embodiment 17, wherein the heat is applied so that the thermo- responsive hydroxylamine NO releasing molecule reaches a temperature of at least 100ºC. [0195] 21. The method of embodiment 17, wherein the heat is applied so that the thermo- responsive hydroxylamine NO releasing molecule reaches a temperature of between 45ºC and 300ºC. [0196] 22. An inhaler including the hydroxylamine NO releasing molecule of any of embodiments 1-16. [0197] 23. The inhaler of embodiment 22, wherein the inhaler is a vaporization device. [0198] 24. A method of treating a disease including inhaling NO released from the hydroxylamine NO releasing molecule of any of embodiments 1-16. [0199] 25. The method of embodiment 24, wherein the method does not include inhaling NO2 with the NO. [0200] 26. A method of synthesizing trityl-diphenyloxazine including: combining trityl chloride of formula of formula to form trityl-diphenyloxazine of formula . of synthesizing 2,5-diphenyloxazine including: combining (9H-fluoren-9-yl)methyl hydroxycarbamate of formula in the presence of piperidine and DMF to form 2,5-diphenyloxazine of the formula . thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments 1-16 in the treatment of pulmonary conditions. [0203] 29. The use of embodiment 28, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0204] 30. Use of the amorphous solid dispersion of any of embodiments 10-12 in the treatment of pulmonary conditions. [0205] 31. Use of the amorphous solid dispersion of embodiment 30, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0206] 32. An inhalation device for the delivery of inhaled NO from the thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments embodiment 1-16, the inhalation device including: a gas intake through which a carrier gas is introduced into the inhalation device; an outlet through which NO is released; an NO generator including a heating element positioned between the intake and the outlet; an NO sensor; and an NO₂ sensor, wherein feedback from the NO sensor and the NO₂ sensor regulates the amount of NO generated by the NO generator. [0207] 33. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 32, wherein in each C_1-20-alkyl-, C_3-8-cycloalkyl-, one CH₂ group may optionally be replaced by CO, SO or SO₂, SO₃, or SiR^N2. [0208] 34. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 33, wherein one CH2 group may optionally be substituted by O or NR^N. [0209] 35. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 34, wherein one H group may optionally be substituted by by C₁-C₂₀ aryl, heteroaryl, or alkyl groups, halogens, OR, or NR. [0210] 36. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 35, wherein R1 is a hydrocarbon polymer. [0211] Third set of Exemplary Embodiments [0212] 1. A thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule having the structure of Formula I: R₅ R1 is hydrogen, C, N, O, P, S, substituted or unsubstituted C1-20- alkyl, or substituted or unsubstituted C3-8-cycloalkyl, and R2, R3, R4, R5, R6, and R7 independently include phenyl (Ph) or H. [0213] 2. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 1, wherein R1 is a triphenyl methyl group of Formula IV: wherein the atom bound to N is the carbon indicated by *, R8, R9, and R10 include a phenyl group, and R8, R9, and R10 can be ortho, meta or para with respect to the carbon bound to the central junction carbon. [0214] 3. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 2, having the structure: . responsive hydroxylamine NO releasing molecule of any of embodiments 1-3, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 45ºC. [0216] 5. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-4, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 100ºC. [0217] 6. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-5, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO within a temperature range of 45 ºC to 300ºC. [0218] 7. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-6, within a porous matrix. [0219] 8. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 7, wherein the porous matrix includes a polymer, lipid, or resin. [0220] 9. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 7, wherein the porous matrix includes an amorphous solid dispersion (ASD). [0221] 10.The thermo-responsive hydroxylamine NO releasing molecule of embodiment 9, wherein the ASD includes a neutral organic polymer. [0222] 11. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 9, wherein the ASD includes a cross-linked polystyrene matrix, a hyper-crosslinked polymer, a porous aromatic framework, a porous organic polymer, a conjugated microporous polymer, and/or a covalent organic framework. [0223] 12. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 8, wherein the polymer includes PAF-1, PIM-1, or polystyrene. [0224] 13. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 8, wherein the resin includes trityl chloride resin, 2-Chlorotrityl chloride resin, DHPP, MBHA, 4- methyltrityl chloride resin, 4-methoxytrityl chloride resin, Hydroxy-(2-chorophnyl)methyl-PS, Rink Acid Resin, Wang resin, or hydroxymethyl phenoxymethyl polystyrene (HMP) resin. [0225] 14. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 8, wherein the resin includes trityl chloride resin. [0226] 15. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 7, wherein the porous matrix has a pore size of 0.5 nm-1 nm. [0227] 16. A method of releasing nitric oxide (NO) from the hydroxylamine NO releasing molecule of embodiment 1, the method including applying heat to the hydroxylamine NO releasing molecule. [0228] 17. The method of embodiment 16, wherein the applying heat includes actuating a vaporization device including a heating element. [0229] 18. The method of embodiment 16 or 17, wherein the heat is applied so that the thermo- responsive hydroxylamine NO releasing molecule reaches a temperature of at least 45ºC. [0230] 19. The method of any of embodiments 16-18, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of at least 100ºC. [0231] 20. The method of any of embodiments 16-19, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of between 45ºC and 300ºC. [0232] 21. An inhaler including the hydroxylamine NO releasing molecule of any of embodiments 1-15. [0233] 22. The inhaler of embodiment 21, wherein the inhaler is a vaporization device. [0234] 23. A method of treating a subject with a condition, the method including inhaling NO released from the hydroxylamine NO releasing molecule of any of embodiments 1-15. [0235] 24. The method of embodiment 23, wherein the method does not include inhaling NO2 with the NO. [0236] 25. A method of synthesizing trityl-diphenyloxazine including: combining trityl chloride of formula of formula to form trityl-diphenyloxazine of formula . thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments 1-15 in the treatment of pulmonary conditions. [0238] 27. The use of embodiment 26, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0239] 28. Use of the amorphous solid dispersion of any of embodiments 9-11 in the treatment of pulmonary conditions. [0240] 29. Use of the amorphous solid dispersion of embodiment 28, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0241] 30. An inhalation device for the delivery of inhaled NO from the thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments embodiment 1-15, the inhalation device including: a gas intake through which a carrier gas is introduced into the inhalation device; an outlet through which NO is released; an NO generator including a heating element positioned between the intake and the outlet; an NO sensor; and an NO2 sensor, wherein feedback from the NO sensor and the NO2 sensor regulates the amount of NO generated by the NO generator. [0242] 31. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 30, wherein in each C_1-20-alkyl-, C_3-8-cycloalkyl-, one CH₂ group may optionally be replaced by CO, SO or SO₂, SO3, or SiRN2. [0243] 32. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 30, wherein one CH2 group may optionally be substituted by O or NRN. [0244] 33. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of claim 1, wherein one H group may optionally be substituted by group optionally by C₁-C₂₀ aryl, heteroaryl, or alkyl groups, halogens, OR, or NR. [0245] 34. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of claim 1, wherein R1 is a hydrocarbon polymer. [0246] Fourth set of Exemplary Embodiments [0247] 1. A thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule having the compound of Formula I: R_{5 7} wherein R₁ is selected from hydrogen, C, N, O, P, S, substituted or unsubstituted C_1-20- alkyl, or substituted or unsubstituted C_3-8-cycloalkyl, R₂, R₃, R₄, R₅, R_6, and R₇ include hydrogen, an alkyl group, a carboxylic acid, esters nitrile, an aromatic group, an ether, an amine, silane, thio/thioether, or a halide, and wherein at least one of R₂, R₃, R₄, R₅, R_6, and R₇ is an aromatic group. [0248] 2. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of embodiment 1 having the structure: . . [0249] 3. The thermo-responsive hydroxylamine NO releasing molecule of embodiment 1 or 2, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 45ºC. [0250] 4. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-3, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 100ºC. [0251] 5. The thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-4, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO within a temperature range of 45 ºC to 300ºC. [0252] 6. An amorphous solid dispersion including the thermo-responsive hydroxylamine NO releasing molecule of any of embodiments 1-5, within a porous matrix. [0253] 7. The amorphous solid dispersion of embodiment 6, wherein the NO releasing molecule is covalently bound to the porous matrix. [0254] 8. The amorphous solid dispersion of embodiment 6, wherein the NO releasing molecule is non-covalently bound to the porous matrix. [0255] 9. The amorphous solid dispersion of any of embodiments 6-8, wherein the porous matrix includes a polymer, lipid, inorganic oxide, alumina, or resin. [0256] 10. The amorphous solid dispersion of any of embodiments 6-8, wherein the porous matrix includes a neutral organic polymer. [0257] 11. The amorphous solid dispersion of any of embodiments 6-8, wherein the porous matrix includes a cross-linked polystyrene matrix, a hyper-crosslinked polymer, a porous aromatic framework, a porous organic polymer, a conjugated microporous polymer, and/or a covalent organic framework. [0258] 12. The amorphous solid dispersion of embodiment 11, wherein the hyper-crosslinked polymer includes HCP-1 or HCP-1-OEt. [0259] 13. The amorphous solid dispersion of embodiment 12, wherein the HCP-1-OEt has been pre-treated with NaOEt. [0260] 14. The amorphous solid dispersion of embodiment 9, wherein the polymer includes PAF- 1, PIM-1, or polystyrene. [0261] 15. The amorphous solid dispersion of embodiment 9, wherein the resin includes trityl chloride resin, 2-Chlorotrityl chloride resin, DHPP, MBHA, 4-methyltrityl chloride resin, 4- methoxytrityl chloride resin, Hydroxy-(2-chorophnyl)methyl-PS, Rink Acid Resin, Wang resin, or hydroxymethyl phenoxymethyl polystyrene (HMP) resin. [0262] 16. The amorphous solid dispersion of embodiment 9, wherein the resin includes trityl chloride resin. [0263] 17. The amorphous solid dispersion of any of embodiments 6-16, wherein the porous matrix has a pore size of 0.5-5 nm. [0264] 18. A method of releasing inhalable nitric oxide (NO) from the hydroxylamine NO releasing molecule of embodiment 1, the method including applying heat to the hydroxylamine NO releasing molecule. [0265] 19. The method of embodiment 18, wherein the applying heat includes actuating an inhalant device including a heating element. [0266] 20. The method of embodiment 18 or 19, wherein the heat is applied so that the thermo- responsive hydroxylamine NO releasing molecule reaches a temperature of at least 45ºC. [0267] 21. The method of any of embodiments 18-20, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of at least 100ºC. [0268] 22. The method of any of embodiments 18-21, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of between 45ºC and 300ºC. [0269] 23. An inhaler including the hydroxylamine NO releasing molecule of any of embodiments 1-5. [0270] 24. The inhaler of embodiment 23, wherein the inhaler is a vaporization device. [0271] 25. A method including inhaling NO released from the hydroxylamine NO releasing molecule of embodiment 1-5. [0272] 26. The method of embodiment 25, wherein the method does not include inhaling NO2 with the NO. [0273] 27. A method of synthesizing trityl-diphenyloxazine including: combining trityl chloride of formula of formula to form trityl-diphenyloxazine of formula . responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments 1-5 in the treatment of pulmonary conditions. [0275] 29. The use of embodiment 28, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0276] 30. Use of the amorphous solid dispersion of any of embodiments 6-17 in the treatment of pulmonary conditions. [0277] 31. Use of the amorphous solid dispersion of embodiment 30, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma. [0278] 32. An inhalation device for the delivery of inhaled NO from the thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of any of embodiments embodiment 1-5, the inhalation device including: a gas intake through which a carrier gas is introduced into the inhalation device; an outlet through which NO is released; an NO generator including a heating element positioned between the intake and the outlet; an NO sensor; and an NO2 sensor, wherein feedback from the NO sensor and the NO2 sensor regulates the amount of NO generated by the NO generator. [0279] 33. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 32, wherein in each C1-20-alkyl-, C3-8-cycloalkyl-, one CH₂ group may optionally be replaced by CO, SO or SO₂, SO₃, or SiR^N . wherein superscript “N” is a whole number. [0280] 34. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 33, wherein one CH₂ group may optionally be substituted by O or NR^N, wherein superscript “N” is a whole number. [0281] 35. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 34, wherein one H group may optionally be substituted by group optionally by C1-C20 aryl, heteroaryl, or alkyl groups, halogens, OR, or NR. [0282] 36. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of Formula I of any of claims 1 to 32, wherein R1 is a hydrocarbon polymer. [0283] (ix) Experimental Examples. General information. Abbreviations used for chemicals include: DMF (dimethylformamide), MeOH (methanol), DMSO (dimethyl sulfoxide), EtOH (ethanol), Et2O (diethyl ether), DCM (dichloromethane), MeCN (acetonitrile), THF (tetrahydrofuran), DMA (dimethylacetamide), and EtOAc (ethyl acetate). Any compound labeled (+/-) x where x is the number identifier for the compound was isolated as a racemic mixture. If relative stereochemistry is not indicated, it is assumed to be a racemic mixture of the cis isomer. [0284] At least some of the material described below was also published in Li S, Blackburn N, Ward C, Bour J. On-Demand Nitric Oxide Generation via Thermal Decomposition of N-Trityl Dihydro-1,2-Oxazines. ChemRxiv. 2024; doi:10.26434/chemrxiv-2024-b9hh5; and Li S, Blackburn NW, Ward CL, Dent MR, Bour JR. On-Demand Nitric Oxide Generation via Thermal Decomposition of N-Trityl Dihydro-1,2-Oxazines. Angew Chem Int Ed Engl. 2025 Mar 10;64(11):e202419113. doi: 10.1002/anie.202419113. Epub 2025 Feb 14. PMID: 39888136. These documents and the related supplemental materials are incorporated herein by reference in their entirety. [0285] Materials. Unless stated otherwise, all commercial reagents were used as received. The procedures described herein involved the following chemicals: (9H-Fluoren-9-yl)methyl hydroxycarbamate (Fmoc-NH-OH) was purchased from Ambeed, Inc; trans,trans-1,4-diphenyl- 1,3-butadiene was purchased from Ambeed, Inc; CuCl was purchased from Alfa Aesar; disodium dihydrogen ethylenediaminetetraacetate dihydrate (disodium EDTA dihydrate) was purchased from Fisher Scientific; MgSO₄ was purchased from Sigma Aldrich; pyridine was purchased from Oakwood Products, Inc.; piperidine was purchased from Sigma Aldrich; trityl chloride was purchased from Ambeed, Inc; triethylamine (NEt₃, anhydrous) was purchased from Sigma Aldrich; tert-butyl hydroxycabamate was purchased from TCI America; 1,3-cyclohexadiene was purchased from Oakwood Products, Inc.; Trifluoroacetic acid (TFA) was purchased from Sigma Aldrich; hydrogen chloride solution, 2.0 M in diethyl ether (2M HCl ether) was purchased from Sigma Aldrich and was stored at 2-8 °C; Aluminium chloride (AlCl3, anhydrous) was purchased from Strem Chemicals, Inc. and was stored at 2-8 °C; 1,3,5-triphenylbenzene was purchased from Sigma Aldrich; N-acetyl-D-penicillamine (NAP) was purchased from Ambeed, Inc; hydrogen chloride (HCl) was purchased from Sigma Aldrich; sulfuric Acid (H2SO4) was purchased from Sigma Aldrich; Sodium hydroxide (NaOH) was purchased from Sigma Aldrich; tert-Butyl (tert- butoxycarbonyl)oxycarbamate was purchased from Ambeed, Inc.; allyl bromide was purchased from Sigma Aldrich; Potassium carbonate (K2CO3) was purchased from Ambeed. Inc.; Magnesium (Mg) was purchased from Sigma Aldrich; 4-bromobiphenyl was purchased from Alfa Aesar; diethyl carbonate was purchased from Acros Organics; Ammonium chloride (NH4Cl, Molecular Biology Grade) was purchased from Calbiochem; acetyl chloride was purchased from Acros Organics; o-allylhydroxylamine hydrochloride was purchased from Ambeed, Inc.; NiBr2 was purchased from Alfa Aesar or Strem, all NiBr2 used was anhydrous. 1,5-cyclooctadiene (COD, freeze-pump-thawed and stored in Schlenk tube in N2 atmosphere glovebox), and zinc dust (activated according to literature1) were purchased from Sigma-Aldrich; 2,2’-bipyridine (bpy) was purchased from Ambeed, Inc.; 4,4-dibromobiphenyl was purchased from Acros Organics; n- butyllithium (n-BuLi, 2.5 M in hexanes) was purchased from Sigma Aldrich; diphenyl carbonate was purchased from Ambeed, Inc.; and poly(styrene-co-divinylbenzene) beads (crosslinked polystyrene beads, Diaion® HP-20, 250-850 μm, activated at 80 ℃ under vacuum for 18 hours before using), 2-chlorotrityl chloride resin (100-200 mesh, 1% divinylbenzene) Aldrich product# # 8550170001; sodium nitrite (NaNO2) was purchased from Thermo Scientific Chemicals; sodium, 99.8%, oiled sticks was purchased from Acros Organic; myoglobin (from equine heart), lyophilized powder was purchased from Sigma Aldrich; sodium hydrosulfite (Na2S2O4) was purchased from Sigma Aldrich; poly(tetrafluoroethylene) (PTFE, powder, > 40 μm particle size) was purchased from Sigma Aldrich. PAF-1 (A. J. Porath, M. A. Hettiarachchi, S. Li, J. R. Bour, Chem. Commun. 2022, 6841–6844) and UiO-67 (A. J. Porath, M. A. Hettiarachchi, S. Li, J. R. Bour, Chem. Commun.2022, 6841–6844) were synthesized according to the literature. [0286] Gas Adsorption Isotherms. Gas adsorption isotherms were determined by a volumetric method using a Micromeritics 3Flex instrument. Samples (~60 mg) were first desolvated overnight under vacuum at 0.1 Torr to remove bulk solvent and other volatile contaminants. The activated samples were transferred to a pre-weighed glass analysis tube capped with a micromeritics TranSeal or CheckSeal. The samples were further activated for 3 hours on a Micromeritics VacPrep 061 (3x10^-2 mmHg). Free space measurements were performed using ultra-high purity He. Nitrogen adsorption isotherms were obtained using ultra-high purity nitrogen and a 77 K liquid-N₂ bath. [0287] Thermogravimetric Analysis (TGA) Thermogravimetric analysis was performed using SDT Q600 TGA–DTA analyzer or TGA Q50 (TA Instruments). ~5-15 mg samples were loaded on alumina/ceramic pans and heated under flowing nitrogen/argon (100 mL min^–1), ramped to the temperature at a rate of 10 °C min^–1. [0288] Powder X-ray Diffraction (PXRD) PXRD patterns were conducted at room temperature using a Bruker Phaser II model X-ray diffractometer with a Cu anode and a Lynxeye detector. The X-ray is generated at 30 kV/10 mA, and the measurements were performed by placing the samples on a quartz holder with zero background.1.0 mm divergence slit, and 3 mm air scatter screen were used. The scanning speed was 0.5 s/step, and the range (2 theta) was from 5° to 50° with 0.02 increment. PSD opening was set at 5.8°. [0289] Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy (SEM-EDS) SEM- EDS was performed on JEOL JSM-7600 field emission SEM equipped with an EDAX Pegasus Apex 2 integrated EDS and EBSD System. Samples were deposited on carbon-coated adhesive tape and the analysis was conducted at an accelerating voltage of 15 kV in high-vacuum mode. The samples on adhesive tape were gold-sputtered prior to the analysis at 200 mTorr for 30 s at an out-put range of 50-100 mA. [0290] UV-Vis Spectroscopy (UV-Vis) UV-Vis spectroscopy was performed on an Agilent Cary 3500 Multicell Spectrophotometer equipped with a Peltier temperature controller. The screw capped quartz cuvettes were loaded with liquid samples and from 800 to 250 nm at 1.00 nm data interval with 3000 nm/min scan rate. [0291] The concentration measurements of NO and NO2 were performed in a flow system using Alphasense NO-A4 and NO2-A43F electrochemical sensors. The flow system was built based on the scheme shown in FIG.3. The generated NO and NO2 were purged out using either high-purity nitrogen from Airgas or lab air as the sweep gas. A 60 cm long 0.060” Nafion^TM tubing from PermaPure was installed before the three-neck sample flask for providing humidity to the system. A bypass was created in parallel to the humidifier, and the humidity range of the system was controlled by adjusting the control valve of CNBTR Gas Flowmeter (0.1-1.0 L/min) in the bypass. The overall flow rate of the combined gas stream together with released gases from sample flask was controlled at 0.5 L/min using Alicat MCS mass flow controller before delivering to the NO/NO₂ electrochemical sensors (for measurements involving compound 3, the activated carbon filter was installed between the outlet of sample flask and the mass flow controller). Both sensors were equipped with an Alphasense Analogue Front End (AFE) circuit board providing +287 mV (NO) and +289 mV (NO₂) bias voltages to both sensors. The output signals from the AFE board were exported to an Arduino UNO microcontroller where the analog signals were converted to digital and read by a PC via USB linkage. A mini digital humidity meter was employed at the end of the gas stream after the sensors for monitoring the real time humidity of the system. The electrochemical NO/NO₂ electrochemical sensors were calibrated using 5.900 ppm Airgas compressed NO gas cylinder (balanced with N2) and 2.950 ppm NO (diluted from 5.900 ppm using N2 by 50/50 vol/vol), and 2.100 ppm Airgas compressed NO2 gas cylinder (balanced with N2) and 1.050 ppm NO2 (diluted from 2.100 ppm using N2 by 50/50 vol/vol). Alicat MCS Series mass flow controllers were used for diluting the calibration gases. [0292] Single crystal X-ray diffraction. Single crystals of compound 6 (C35H29NO) were grown by vapor diffusion of isopropanol into toluene. A suitable colorless crystal (0.08 x 0.10 x 0.10) mm3 was mounted on a MicroMount (MiTeGen) with paratone oil (Parabar 10312, Hampton Research) on a Bruker D8 Venture diffractometer with kappa geometry, an Incoatec IμS micro- focus source X-ray tube (Cu Kα radiation), and a multilayer mirror for monochromatization. The X-ray diffraction intensities were measured using a Photon III CPAD area detector at a distance of 38 mm. Data were acquired at 100 K with an Oxford 800 Cryostream low-temperature apparatus. The crystal contained three domains that were determined using the Domain feature in APEX5 v2023.9-2. Using APEX5, the intensities were integrated using SAINT V8.40B and a multiscan absorption correction was applied to all domains with TWINABS v2012/1. The HKLF-4 file was created with all three domains and used to solve the structure and one domain was used to generate the HKLF-5 file for refinement. The crystal structure was solved using a dual-space approach as implemented in SHELXT[4] and difference Fourier (ΔF) maps during least-squares refinement, as embedded in SHELXL-2019/3[5] running under Olex2[6]. All non-hydrogen atoms were refined anisotropically. The hydrogen atoms were positioned with idealized geometry and refined isotropically using a riding model. At 100 K, the crystal structure was solved in the chiral space group P21 with two crystallographically independent enantiomers in the asymmetric unit and Z=4. The two molecules are related to each other by a pseuodoinversion center and have essentially the same conformation (see figure in Single Crystal X-ray Diffraction Data section), which is an interesting case of an organic kryptoracemate crystal.[7,8] The crystal contained three domains due to non-merohedral twinning (180° rotation around the [-10 -1] reciprocal cell) and crystal imperfection (77° rotation around the [-2105] reciprocal cell). Final refinement gave batch scale factors of 0.511(3) and 0.029(3), respectively. The Flack parameter is -0.030(133) by classical methods and -0.224(156) by Parsons’ method, however, the synthesis did not control for chirality thus racemic mixture was expected. [0293] Synthesis. Bicyclicoxazine (compound 2) synthesis. , a mm bar. Then 1,3 cyclohexadiene (880 uL, 9.2 mmol, 1.2 equiv) was added via syringe followed by CuCl (150 mg, 1.52 mmol, 0.20 equiv.) and pyridine (30 µL, 0.38 mmol, 0.05 equiv.). The reaction was allowed to be stirred under air at 23°C for 3 hours, and then quenched with 160 ml 0.5M EDTA. The product was extracted by ethyl acetate (160 ml × 3), and the combined organic layers were dried over MgSO4. A yellow oil was obtained in 1.54 g (96% yield) after rotary evaporator as the product compound 1.¹H NMR (400 MHz, cdcl3) δ 6.54 (tt, J = 8.3, 4.0 Hz, 2H), 4.73 (dt, J = 5.4, 2.7 Hz, 2H), 2.29 – 1.99 (m, 2H), 1.53 – 1.48 (m, 1H), 1.46 (s, 9H), 1.39 – 1.29 (m, 1H). Under open air, a 20 ml glass scintillation vial was charged with compound 1 (1.11 g, 5.3 mmol, 1.0 equiv.), 7 ml of anhydrous DCM, and a 10 mm PTFE magnetic stir bar. The resulting solution was stirred vigorously, and 4 ml of TFA (52 mmol, 9.9 equiv.) was measured and added dropwise via syringe. After 4 hours (or no gas bubbles observed), the solvent was removed under a stream of nitrogen overnight to obtain a viscous purple oil, which was then re-dissolved in 4 ml Et₂O and precipitated by adding 5 ml 2M HCl etherate. The obtained white precipitates were collected by a medium size frit, washed with Et₂O (4 ml × 2) and dried under vacuum to yield an off-white solid as compound 2 in 680 mg (88% yield).¹H NMR (400 MHz, dmso) δ 6.84 (dd, J = 8.2, 6.1 Hz, 1H), 6.59 (dd, J = 8.3, 6.4 Hz, 1H), 4.97 (t, J = 4.2 Hz, 1H), 4.56 (d, J = 6.0 Hz, 1H), 2.09 (dtd, J = 15.7, 10.7, 10.2, 6.7 Hz, 2H), 1.50 –1.38 (m, 2H). [0294] Trityl-bicyclicoxazine (compound 3) synthesis. mg, 0.38 mmol, 1.7 equiv.), 2.5 ml anhydrous DCM, and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (0.46 ml, 3.3 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass vial, trityl chloride (61 mg, 0.22 mmol, 1 equiv.) was charged into it and dissolved in 1 ml of anhydrous DCM under nitrogen, and the resulting solution was transferred to the first vial drop wisely using a needle and a syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 18 hours. The volatiles were removed under a stream of nitrogen and the obtained crude solids were washed by 2 ml methanol (with 2 drops of triethylamine added). The white precipitates were filtered and dried under vacuum at room temperature for 30 min to yield 54 mg (70% yield) compound 3 as product.¹H NMR (400 MHz, cdcl3) δ 7.56 (d, J = 7.7 Hz, 6H), 7.21 (td, J =7.4, 6.7, 1.2 Hz, 6H), 7.16 – 7.09 (m, 3H), 5.67 (ddd, J = 7.4, 5.7, 1.5 Hz, 1H), 5.13 (ddd, J = 7.9, 6.0, 1.6Hz, 1H), 4.23 (d, J = 1.8 Hz, 1H), 4.00 (s, 1H), 2.44 (td, J = 9.2, 3.9 Hz, 1H), 2.30 (td, J = 8.9, 3.5 Hz, 1H), 1.27 (dd, J = 8.6, 1.6 Hz, 2H). [0295] Diphenyloxazine ((+/-) 5) synthesis. hydroxycarbamate (612 mg, 2.4 mmol, 1 equiv.) and trans,trans-1,4-diphenyl-1,3-butadiene (592 mg, 2.88 mmol, 1.2 equiv.) together with a 25 mm PTFE magnetic stir bar. The solids mixture was dissolved in 24 ml of THF before adding CuCl (47.2 mg, 0.48 mmol, 0.2 equiv.) and pyridine (9.6 µL, 0.03 mmol, 0.05 equiv.). The resulting mixture was stirred at 23 ℃ for 20 hours under air which was then quenched by adding 48 ml of 0.5 M EDTA aqueous solution. The product was extracted by ethyl acetate (50 ml × 3). The organic layers were combined, dried over MgSO₄, and the volatiles were removed by rotary evaporator to isolate the crude product. The obtained light-yellow product was further purified by performing silica column chromatography using hexanes/ethyl acetate and the transparent oil was isolated as the racemic mixture of compound 4 (+/-) 4 in 457 mg (43% yield).¹H NMR (400 MHz, cdcl3) δ 7.75 (dp, J = 7.6, 0.9 Hz, 2H), 7.60 (dd, J = 20.6, 7.5 Hz, 2H), 7.48 (d, J = 7.4Hz, 2H), 7.43 – 7.20 (m, 13H), 6.18 – 6.11 (m, 1H), 6.08 (dt, J = 10.2, 1.5 Hz, 1H), 5.57 (s, 1H), 5.52 (d, J = 3.2 Hz, 1H), 4.59 (dd, J = 10.6, 6.6 Hz, 1H), 4.52 (dd, J = 10.5, 7.2 Hz, 1H), 4.26 (t, J = 6.9 Hz, 1H). to the compound (+/-) 4 isolated from the previous step. The obtained solution was stirred for 10 min with a 25 mm PTFE magnetic stir bar and turned into yellow gradually. The solvent was removed by blowing a nitrogen stream overnight, and the crude product was purified by silica column chromatography using hexanes/ethyl acetate to yield 207 mg (82% yield) racemic mixture of 2,5- diphenyloxazine (+/-) 5 as a yellow oil.¹H NMR (400 MHz, cdcl3) δ 7.57 – 7.27 (m, 10H), 6.22 (s, 2H), 5.37 (d, J = 2.8 Hz, 1H), 4.75 (d, J = 3.1 Hz, 1H). 13C NMR (101 MHz, cdcl3) δ 128.66, 128.56, 128.40, 128.31, 128.28, 128.24, 128.02, 127.97, 77.25, 77.23, 59.67, 59.66. [0296] N-trityl-diphenyloxazine ((+/-) 6)synthesis. Under nitrogen, a 20 ml glass scintillation vial was charged with the compound (+/-) 5 (97 mg, 0.41 mmol, 1.5 equiv.), 1.5 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt₃ (0.56 ml, 4.1 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, trityl chloride (75 mg, 0.27 mmol, 1 equiv.) was charged into it and dissolved in 1 ml of anhydrous DCM under nitrogen, and the resulting solution was transferred to the first vial drop wisely using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 18 hours. The obtained yellow solution was then dried by blowing nitrogen stream and the crude solids were washed by 2 ml methanol (with 2 drops of NEt₃ added). The white precipitates were collected by filtration using a medium size frit and dried under vacuum at room temperature for 30 min to yield 103 mg (80% yield) of racemic mixture (+/-) 6 as product.¹H NMR (400 MHz, cdcl3) δ 7.57 – 7.28 (m, 10H), 7.24 (d, J = 1.9 Hz, 1H), 7.18 – 6.83 (m, 14H), 5.97 (ddd, J = 12.0, 4.2, 1.9 Hz, 1H), 5.93 – 5.85 (m, 1H), 5.62 (s, 1H), 5.10 (d, J = 4.3 Hz, 1H).13C NMR (101 MHz, cdcl3) δ 143.64, 140.73, 130.52, 129.93, 129.02, 128.37, 127.91, 127.79, 127.67, 126.94, 126.24, 125.93, 125.42, 78.17. [0297] 2-Chlorotrityl resin-diphenyloxazine ((+/-) 13) synthesis. mmol, 0.25 equiv.), 1 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (0.05 ml, 0.38 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, 2-chlorotrityl chloride resin (68 mg, 0.10 mmol, 1 equiv, aldrich product #8550170001) was charged into it and soaked in 1 ml of anhydrous DCM under nitrogen for 1 hour before the solution from the first vial was transferred to it using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 18 hours. The obtained yellow solution was then dried by blowing nitrogen stream and the crude solids were washed by 2 ml methanol (with 2 drops of NEt₃ added). The yellowish orange precipitates were collected by filtration using a medium size frit and dried under vacuum at room temperature for 30 min to yield 74 mg (100% yield) of racemic mixture (+/-) 13 as product. [0298] Trityl-resin-diphenyloxazine ((+/-) 19) synthesis Under nitrogen, a 20 ml glass scintillation vial was charged with the compound (+/-) 5 (51 mg, 0.216 mmol, 1.2 equiv.), 1 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (0.425 ml, 2.7 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, trityl chloride resin (120 mg, 0.18 mmol, 1 equiv, Advanced ChemTech product #SC5028) was charged into it and soaked in 3 ml of anhydrous DCM under nitrogen for 1 hour before the solution from the first vial was transferred to it using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 18 hours. The obtained yellow-orange solution was then dried by blowing nitrogen stream and the crude solids were washed by 2 ml methanol (with 2 drops of NEt3 added). The yellowish orange precipitates were collected by filtration using a medium size frit and dried under vacuum at room temperature for 30 min to yield racemic mixture (+/-) 19 as product. [0299] n-Allylhydroxylamine (compound 8) synthesis. A 250 ml round bottom flask was charged with tert-Butyl (tert-butoxycarbonyl)oxycarbamate (10 g, 42.9 mmol, 1 equiv.), 80 ml of degassed anhydrous DMF, K2CO3 (8.3 g, 60.1 mmol, 1.4 equiv.), and allyl bromide (7.4 ml, 85.5 mmol, 2 equiv.). The mixture was stirred for 5 hours then diluted with 40 ml of DI water before extracting with EtOAc (75 ml×2). The organic layers were combined and washed with 40 ml of saturated NaCl solution, then dried with MgSO4. The volatiles were removed using rotary evaporator and the crude residue was dried overnight under vacuum. The obtained viscous yellow oil was then diluted with 100 ml of heptane and the volatiles were removed using rotary evaporator. This process was repeated using additional 25 ml of heptane and the isolated product was further dried under vacuum overnight to afford 9.6 g (82% yield) yellow oil as the product (compound 7). Under air, a 20 ml glass scintillation vial was charged with the compound 7 (1 g, 3.7 mmol, 1 equiv.), 7 ml of anhydrous DCM, and a 10 mm PTFE magnetic stir bar. Then TFA (5.5 ml, 71.9 mmol, 19.4 equiv.) was measured and added to the reaction mixture using syringe. The reaction was allowed to be stirred under air at 23 ℃ for 18 hours then concentrated by blowing nitrogen stream. The obtained red viscous oil was diluted by 2 ml Et2O before adding 4 ml 2M HCl etherate. The reddish-yellow oil percipient was isolated by pipetting out the Et2O layer and dried under vacuum for 2 hours to afford 390 mg (97% yield) compound 8 as the product. [0300] N-trityl-n-allylhydroxylamine (compound 9) synthesis. Under nitrogen, a 20 ml glass scintillation vial was charged with the compound 8 (211.5 mg, 1.9 mmol, 1.5 equiv.), 3 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (2.7 ml, 19.4 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, trityl chloride (360 mg, 1.29 mmol, 1 equiv.) was charged into it and dissolved in 3 ml of anhydrous DCM under nitrogen, and the resulting solution was transferred to the first vial drop wisely using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 4 hours. The obtained solution was then dried by blowing nitrogen stream, and the crude solids were washed by 10 ml 0.5 M K2CO3 and extracted by DCM (10 ml×2). The combined organic layers were dried over MgSO4 and isolated using rotary evaporator. The obtained yellow oil was purified by silica column chromatography using hexanes/ethyl acetate (basified by 1% NEt3) to afford compound 9 as product. [0301] Ph-trityl chloride (compound 15) synthesis. Inside a N₂-filled glovebox, a 100 ml Schlenk tube was charged with Mg (418 mg, 17.2 mmol, 4.5 equiv., the surface was scratched to activate the reaction sites), 40 ml degassed anhydrous THF, and a 25 mm PTFE magnetic stir bar. It was then sealed by a rubber septum and transferred from glovebox to a Schlenk line. Under positive N₂ pressure, a tip of iodine was added to the tube and the reaction mixture turned into orange immediately.4-Bromobiphenyl solution was then prepared by dissolving 4-bromobiphenyl (4 g, 17.2 mmol, 4.5 equiv.) in 5 ml of degassed anhydrous THF inside the glovebox which was added drop wisely to the Schelnk tube using needle and syringe. The obtained reaction mixture was allowed to stir at 23 ℃ for 5 hours which the color was turned gradually from yellow to green. Diethyl carbonate (0.46 ml, 3.8 mmol, 1 equiv.) was then added to the mixture using needle and syringe and the reaction was stirred at 23℃ for additional 18 hours. The obtained dark brown solution was quenched by adding 5 ml of DI water, 2 ml saturated NH4Cl aqueous solution and 2 ml brine. The organic layer was then separated, and the aqueous layer was washed with Et2O (20 ml×2) and EtOAc (20 ml×1). The combined organic layers were dried over MgSO4, and the solvent was removed by rotary evaporator. The obtained yellowish- green oil was subjected to 10 ml of MeOH, and the obtained white precipitates were collected by a medium size frit to afford 800 mg (43% yield) compound 14 as the product.

A 20 ml glass scintillation vial was charged with compound 14 (170 mg, 0.35 mmol, 1 equiv.), 10 ml anhydrous toluene, acetyl chloride (250 µL, 3.5 mmol, 10 equiv.), and a 10 mm PTFE magnetic stir bar. The reaction mixture was allowed to be stirred at 80 ℃ for 18 hours and the resulting light pink solution was dried by blowing nitrogen stream. The obtained solids (compound 15) were directly carried forward for further synthesis. [0302] Ph-trityl-n-allylhydroxylamine (compound 10) synthesis. 1.5 equiv.), 1 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (0.73 ml, 5.25 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, compound 15 (177 mg, 0.35 mmol, 1 equiv.) was charged into it and dissolved in 1 ml of anhydrous DCM under nitrogen, and the resulting solution was transferred to the first vial drop wisely using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 18 hours. The obtained solution was then dried by blowing nitrogen stream, and the crude solids were washed by 20 ml 0.5 M K2CO3 and extracted by DCM (20 ml×2). The combined organic layers were dried over MgSO4 and isolated using rotary evaporator. The obtained clear yellow oil was further washed by 2 ml MeOH and dried over vacuum to afford compound 10 as product. [0303] Trityl-o-allylhydroxylamine (compound 11) synthesis.

Under nitrogen, a 20 ml glass scintillation vial was charged with the o-allylhydroxylamine hydrochloride (326 mg, 2.9 mmol, 1.5 equiv.), 15 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (4 ml, 28.7 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, trityl chloride (540 mg, 1.9 mmol, 1 equiv.) was charged into it and dissolved in 3 ml of anhydrous DCM under nitrogen, and the resulting solution was transferred to the first vial drop wisely using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 4 hours. The obtained solution was then dried by blowing nitrogen stream, and the crude solids were washed by 20 ml 0.5 M K2CO3 and extracted by DCM (20 ml×2). The combined organic layers were dried over MgSO4 and isolated using rotary evaporator. The obtained solids were dried over vacuum to afford compound 11 as product. [0304] Ph-trityl-o-allylhydroxylamine (compound 12) synthesis. hydrochloride (58 mg, 0.53 mmol, 1.5 equiv.), 1 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (0.73 ml, 5.25 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, compound 15 (177 mg, 0.35 mmol, 1 equiv.) was charged into it and dissolved in 1 ml of anhydrous DCM under nitrogen, and the resulting solution was transferred to the first vial drop wisely using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 ℃ for 18 hours. The obtained solution was then dried by blowing nitrogen stream, and the crude solids were washed by 20 ml 0.5 M K2CO3 and extracted by DCM (20 ml×2). The combined organic layers were dried over MgSO4 and isolated using rotary evaporator. The obtained clear yellow oil was further washed by 2 ml MeOH and dried over vacuum to afford compound 12 as product. [0305] Hyper crosslinked polymer framework (HCP-1) synthesis. filled glovebox, a 100 ml Schlenk flask was charged with anhydrous AlCl₃ (2.5 g, 18.8 mmol, 7.8 equiv.), 1,3,5-triphenylbenzene (0.75 g, 2.4 mmol, 1.0 equiv.), and a 25 mm PTFE magnetic stir bar. A condenser was attached on the top of the Schlenk flask, and the overall set-up was sealed on top by a septum and transferred to the Schlenk line. Under positive N2 atmosphere, 30 ml of degassed anhydrous DCM was injected into the reaction flask from top by a syringe and a needle, and the generated HCl was allowed to come out from top through a needle and was quenched by aqueous NaOH solution. The reaction mixture was stirred under refluxing (60°C) for 20 hours, and then cooled to room temperature. The resulting mixture was further cooled in an ice-water bath and filtered by a medium size frit. The obtained dark brown solids were washed with DI water until the filtrate was neutral. The additional washes were performed with EtOH (50 ml×5) and THF (50 ml×5), and the obtained reddish-brown solids were dried under vacuum at 80 ℃ overnight to yield 1.02 g (129% yield) product. The average BET surface area between different batches was measured as 2400 +/- 260 m² g^-1as determined by N₂ adsorption isotherms. No significant variations were noticed between batches with respect to NO release performance. SEM-EDX element wt%: CK: 91.70, OK: 6.08, AlK: 0.30, ClK: 1.91. [0306] Hyper crosslinked polymer framework (HCP-1-OEt) synthesis The benzylic chloride defects of HCP-1 were quenched by sodium ethoxide using the following procedure. Under air, a 100 ml round bottom flask was charged with 18.5 ml EtOH and a 25 mm PTFE magnetic stir bar.42 mg sodium metal was added to the EtOH in two portions under stirring. Once all the sodium metal dissolved, 200 mg HCP-1 was added to the flask and the resulting mixture was allowed to stir at room temperature for 2 hours before heating up to 40 ℃. The reaction was allowed to stir for additional 18 hours and then the reddish-brown solids were filtered, washed with EtOH (15 ml×3), water (15 ml×3), EtOH (15 ml×3), THF (15 ml×3), and dried under vacuum at 80 ℃ overnight to yield 178 mg as the product. The BET surface area was measured as 1794 m² g^{-1 1}as determined by N₂ adsorption isotherms. SEM-EDX element wt%: CK: 88.58, OK: 10.73, AlK: 0.20, ClK: 0.49. [0307] Procedure of PAF-1 synthesis. dried solid addition funnels and an oven dried Claisen adapter. The solid addition funnel for the monomer was equipped with a stir bar and a magnet which was electrical taped to the outside. The top port of the Claisen adapter was fitted with a septum and the side was fitted with a hose barb adapter. All joints were greased and clipped and the reaction vessel was cooled under vacuum. Once cooled, the vessel was backfilled with N₂. One solid addition funnel was filled with activated zinc dust (1.68 g, 25.7 mmol) and the other filled with tetrakis(4-bromophenyl)methane (2.7 g, 4.25 mmol). The vessel was loaded with NiBr2 (4.49 g, 20.55 mmol), bipy (6.42 g, 41.14 mmol), and evacuated and refilled three times. DMF was then added via cannula (180 mL), followed by the addition of COD (7.7 mL, 62.53 mmol, via syringe). The reaction was then heated to 80°C for 1 hour, followed by the addition of the activated zinc dust via the solid addition funnel. After stirring for 5 min, the monomer was added via the other solid addition funnel. The stir bar inside the funnel was manipulated using the magnet on the outside of the funnel to break up any clumps precluding smooth addition of the solid. The reaction stirred for 22 hours at 80°C. It was then cooled to room temperature, dumped into a 500 mL beaker under air, and quenched with 6 M HCl (100 mL). The quench stirred for 19 hours open to air, and the polymer was collected via vacuum filtration with a M fritted funnel. The filter residue was washed with 100 mL each of DMF, MeOH, CH2Cl2, CHCl3, and THF. It was then dried under vacuum at 80°C and the polymer was obtained as a white solid (1.21 g, 90% yield based on theoretical structure). The BET surface area of polymer obtained through this procedure was 4450 m2 g-1 as determined from N2 isotherms at 77 K. [0308] Synthesis of porous organic framework TAF-OH (compound 16), TAF-Cl (compound 17), and TAF-diphenyloxazine (compound 18). dibromobiphenyl (5 g, 16 mmol, 1.5 equiv.), 100 ml degassed anhydrous THF, and a 25 mm PTFE magnetic stir bar. The solution was then transferred to a Schlenk line and cooled to -78 °C using a dry ice/acetone bath.2.5 M n-BuLi (14 ml, 35 mmol, 3.0 equiv.) was then added into it under positive N₂ pressure using a syringe and a needle, and the resulting mixture was allowed to be stirred for 2.5 h. After that, the cold bath was removed and the reaction mixture was allowed to warm up to 23 °C. Inside the N₂-filled glovebox, diphenyl carbonate (2.4 g, 11 mmol, 1 equiv.) was dissolved in degassed anhydrous THF and the resulting solution was transferred and added into the Schlenk flask drop wisely using a needle and a syringe. The yellow viscous suspension was allowed to be stirred at 23 °C for 18 hours before adding 28 ml of MeOH and 4 ml concentrated HCl. The obtained precipitates were isolated by vacuum filtration using a medium size frit and washed with DI water until the pH was neutral. The obtained off-white solids were dried under vacuum at 120 °C for 18 hours and then further activated using the high vacuum for additional 19 hours (1 hour at room temperature and 18 hours at 120 °C).

A 20 ml glass scintillation vial was charged with compound 16 (38.6 mg, 0.15 mmol, 1 equiv.), 7 ml anhydrous toluene, acetyl chloride (107 µL, 1.5 mmol, 10 equiv.), and a 10 mm PTFE magnetic stir bar. The reaction mixture was allowed to be stirred at 80 °C for 18 hours and the resulting light pink solution was dried by blowing nitrogen stream. The obtained solids (compound 17) were directly carried forward for further synthesis. mg, 0.23 mmol, 1.5 equiv.), 1.5 ml anhydrous DCM and a 10 mm PTFE magnetic stir bar. Anhydrous NEt3 (0.32 ml, 2.25 mmol, 15 equiv.) was then added to the solution and the resulting mixture was allowed to stir under nitrogen for about 1 min. In another 20 ml glass scintillation vial, compound 17 (39 mg, 0.15 mmol, 1.0 equiv.) was charged into it together with 1 ml anhydrous DCM, and the solution from the first vial was transferred to it using needle and syringe. The combined mixture was allowed to stir under nitrogen at 23 °C for 18 hours. The obtained yellow solution was then dried by blowing nitrogen stream and the crude solids were washed by 2 ml methanol (with 2 drops of NEt3 added). The white precipitates were collected by filtration using a medium size frit and dried under vacuum at room temperature for 30 min to yield 69 mg (100% yield) of compound 18 as product. [0309] General procedures of doping NO donor molecules in in porous supporting matrix. In general, compound (+/-) 6 was mixed together with the porous supporting matrix (hyper crosslinked polymer framework or activated poly(styrene-co-divinylbenzene beads)) in certain weight percentage (0.1 - 100 % by weight ), and the obtained mixture was dissolved in DCM (3 ml per 100 mg solid mixture) and swirled for 30 sec. The mixture was allowed to dry in the fume hood at 23 ℃ for 18 hours allowing slow evaporation of the solvent. The material was further dried by applying vacuum for 30 min and stirred by a spatula to yield a uniform mixture. The release curve of compound 6 dispersed in polystyrene beads under a stream of air or N2 is shown in FIG. 9C. [0310] General procedures of NO release measurement. Typically, 10 mg ± 0.5 mg of the sample was measured and carefully loaded into a 25 ml three-neck round bottom flask which was then installed in the NO/NO₂ measurement flow system. The sweeping gas (either N₂ or air) was then turned on and the flow rate was controlled by a mass flow controller at 0.5 L/min with the humidity between 40-60%. The NO/NO₂ sensors were allowed to stabilize for at least 10 min before applying the heat to the three-neck flask using a hot oil bath at certain temperatures (e.g., 150 ℃). The real-time concentration of NO and NO₂ was recorded every 1 second. The measurement was continued until the concentration of both NO and NO2 dropped back to the baseline. [0311] Bench stability study of N-trityl-diphenyloxazine (compound 6) in hyper crosslinked polymer framework. Based on general procedure, a batch of 1.00 g material containing 15 wt% (+/-) 6 was made based on the general procedure. The obtained material was stored in dark at ambient environment. The NO release measurements were performed using NO/NO₂ flow measurement system following the general procedure at day 1, day 2, day 4, day 7, day 10, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 11 weeks. Triplicate measurements were taken at each day point for getting averages. [0312] Bench stability evaluation of compound 3 in HCP-1 A batch of 100 mg material containing 15 wt% of compound 3 was made based on the general procedure described above. The obtained material was stored in dark at ambient environment. The NO release measurements were performed using NO/NO₂ flow measurement system following the general procedure at day 0, day 4, day 8, day 12, day 19, and day 27. [0313] Bench stability evaluation of compound 3 in HCP-1-OEt Two batches of 100 mg material containing 15 wt% of compound 3 were made based on the general doping procedure described above. The obtained material was stored in dark at ambient environment. The NO release measurements were performed using NO/NO₂ flow measurement system following the general procedure at day 1, day 3, day 5, day 7, day 10, day 14, day 21, day 28, and day 35. One measurement was taken at each day point of the two different batches, respectively. The releasing profiles were reported as the average of the two batches. [0314] Bench stability evaluation of compound 6 in HCP-1 A batch of 1.00 g material containing 15 wt% compound 6 was made based on general doping procedure described above. The obtained material was stored in dark at ambient environment. The NO release measurements were performed using NO/NO₂ flow measurement system following the general procedure at day 1, day 2, day 4, day 7, day 10, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 11 weeks. Three duplicated measurements were taken at each day point for getting averages. [0315] Bench stability evaluation of compound 6 in HCP-1-OEt A batch of 100 mg material containing 15 wt% compound 6 was made based on general doping procedure. The obtained material was stored in dark at ambient environment. The NO release measurements were performed using NO/NO2 flow measurement system following the general procedure described in section 3.8 at day 1, day 3, day 5, day 7, day 10, day 14, day 21, day 28, and day 35. One measurement was taken at each day point of the two different batches, respectively. The releasing profiles were reported as the average of the two batches. [0316] General procedures of control measurements Cross sensitivity tests of probable reaction products: Triphenylmethanol, and trans, trans-1,4-diphenyl-1,3-butadiene were pre-dispersed in HCP-1 in 15 wt% using DCM. Typically, 10 mg of hyper crosslinked S11 polymer HCP-1, 10 mg of hyper crosslinked polymer HCP-1-OEt, 4.6 mg of trans,trans-1,4-diphenyl-1,3-butadiene in HCP-1 (15 wt%, 3.1 μmol), 5.4 mg of triphenylmethanol in HCP-1 (15 wt%, 3.1 μmol), 3 mg of compound 5, 10 μL DCM, or 10 μL MeOH was measured and carefully loaded into a 50 ml three- neck round bottom flask which was then installed in the NO/NO2 measurement flow system (all control measurements were performed without the carbon filter). The N2 sweeping was then turned on and the flow rate was controlled by a mass flow controller at 0.5 L/min with the humidity between 40-60% (humidity was not found to significantly affect yield). The NO/NO2 sensors were allowed to stabilize under flow for at least 10 min before applying the heat to the three-neck flask using a hot oil bath at certain temperatures. The real-time concentration of NO and NO2 were recorded every 1 second. [0317] Cross-sensitivity study of 1,3-cyclohexadiene with NO/NO2 sensors A stock solution was made by dissolving 9 μL 1,3-cyclohexadiene in 591 μL DMSO (0.015 vol%) using micropipettes. 20 μL of the stock solution (0.3 μL, 3 μmol of 1,3-cyclohexadiene) was measured using micropipettes and injected into the three-neck sample flask in the flow system for cross-sensitivity measurements. N₂ was used as sweep gas and the overall flow rate was controlled at 0.5 L/min with the humidity between 40-60%. The measurements were performed at room temperature either with or without the carbon filter. [0318] NO release kinetics study in aqueous with oxymyoglobin assay The following procedure was adapted from Pinto (R. V. Pinto, C.-C. Cao, P. Lyu, I. Dovgaliuk, W. Shepard, E. Rivière, C.- Y. Su, G. Maurin, F. Antunes, J. Pires, V. André, C. Henriques, A. Tissot, M. L. Pinto, C. Serre, Small 2024, 20, 2405649.) NO release from compounds 3 and 6 in HCP-1-OEt into aqueous solution was quantified using the oxymyoglobin assay. Oxyferrous myoglobin solution was prepared by dissolving 34 mg of lyophilized equine myoglobin in 1 ml N₂-purged phosphate- buffered saline (pH 7.4, PBS) solution. Chemical reduction of ferric myoglobin was accomplished by addition of 250 µl of Na2S2O4 stock solution (22 mM in N2-purged PBS buffer) to the myoglobin stock. Simultaneous removal of excess sodium dithionite and oxygen binding were carried out by passing the myoglobin solution through a BIO-RAD 10DG desalting column. The concentration of the resulting oxymyoglobin solution was measured using UV-Vis spectrophotometer as 654 μM. Compound 3 in HCP-1-OEt (1.9 mg, contained 15 wt% donor, 0.8 μmol, 1 eq.), compound 6 in HCP-1-OEt (2.6 mg, contained 15 wt% donor, 0.8 μmol, 1 eq.), and HCP-1-OEt (2.0 mg) were mixed with PTFE powder by 1 wt% individually and pressed into 13 mm pellets under 2.5 metric tons pressure using a pellet press. Four identical cuvettes were charged with oxymyoglobin solution (24.4 μL, 0.2 eq.) and diluted into 800 μL using PBS buffer solution. Three sample pellets were cut into smaller pieces and 1/10 of each sample pellets were added into three different cuvettes. All four cuvettes were then incubated at 37 ℃ in the UVVis spectrophotometer, and scans recorded every 5 min for 20 hours. [0319] Procedure for studying dispersion crystallinity based on mixing: Compounds 3 and 6 were doped in HCP-1 by 15 wt% using different methods including solvent assisted dispersing (DCM), hand mixing, and grinding by mortar and pestle. Compound 3 was doped in other supporting matrix — HCP-1-OEt, PAF-1, UIO-67, and silica by 15 wt% using solvent assisted dispersing (DCM). SNAP was doped in HCP-1 using solvent assisted dispersion (MeOH). The PXRD of these materials were performed and compared to the pure donor molecule. The purpose of this experiment was to confirm the amorphous solids dispersion obtained from solvent assisted doping method as opposed to any obfuscation of the diffraction that may occur due to simple physical mixing (i.e. crystallites dispersed around polymer particles). Hand mixed refers to simple agitation of the two solids with a spatula. Ground mixing refers to mixing of the polymer with the donor using a mortar and pestle. As can be seen below, grinding and hand mixing of the crystallites with the polymer particles still resulted in observable diffraction, suggesting that the lack of diffraction seen in solvent dispersed samples is due to the destruction of significant crystalline domains. [0320] (x) Closing Paragraphs. As will be understood by one of ordinary skill in the art, each embodiment disclosed herein can comprise, consist essentially of or consist of its particular stated element, step, ingredient or component. Thus, the terms “include” or “including” should be interpreted to recite: “comprise, consist of, or consist essentially of.” The transition term “comprise” or “comprises” means has, but is not limited to, and allows for the inclusion of unspecified elements, steps, ingredients, or components, even in major amounts. The transitional phrase “consisting of” excludes any element, step, ingredient or component not specified. The transition phrase “consisting essentially of” limits the scope of the embodiment to the specified elements, steps, ingredients or components and to those that do not materially affect the embodiment. A material effect would cause a statistically significant reduction in shelf-stability and/or a statistically significant increase in NO2 contamination. [0321] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. When further clarity is required, the term “about” has the meaning reasonably ascribed to it by a person skilled in the art when used in conjunction with a stated numerical value or range, i.e. denoting somewhat more or somewhat less than the stated value or range, to within a range of ±20% of the stated value; ±19% of the stated value; ±18% of the stated value; ±17% of the stated value; ±16% of the stated value; ±15% of the stated value; ±14% of the stated value; ±13% of the stated value; ±12% of the stated value; ±11% of the stated value; ±10% of the stated value; ±9% of the stated value; ±8% of the stated value; ±7% of the stated value; ±6% of the stated value; ±5% of the stated value; ±4% of the stated value; ±3% of the stated value; ±2% of the stated value; or ±1% of the stated value. [0322] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. [0323] The terms “a,” “an,” “the” and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention. [0324] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims. [0325] Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context. [0326] Furthermore, numerous references have been made to patents, printed publications, journal articles and other written text throughout this specification (referenced materials herein). Each of the referenced materials are individually incorporated herein by reference in their entirety for their referenced teaching. [0327] It is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described. [0328] The particulars shown herein are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of various embodiments of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for the fundamental understanding of the invention, the description taken with the drawings and/or examples making apparent to those skilled in the art how the several forms of the invention may be embodied in practice. [0329] Definitions and explanations used in the present disclosure are meant and intended to be controlling in any future construction unless clearly and unambiguously modified in the example(s) or when application of the meaning renders any construction meaningless or essentially meaningless. In cases where the construction of the term would render it meaningless or essentially meaningless, the definition should be taken from Webster's Dictionary, 11th Edition or a dictionary or reference well-known to and used by those of ordinary skill in the art.

Claims

LISTING OF CLAIMS What is claimed is: 1. A thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule having the structure of Formula I: R_{5 7} wherein R1 is selected from hydrogen, C, N, O, P, S, substituted or unsubstituted C1-20- alkyl, or substituted or unsubstituted C3-8-cycloalkyl; R2, R3, R4, R5, R6, and R7 are selected from hydrogen, an alkyl group, a carboxylic acid, esters nitrile, an aromatic group, an ether, an amine, silane, thio/thioether, or a halide, and wherein at least one of R2, R3, R4, R5, R6, and R7 is an aromatic group.

2. The thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of claim 1 having the structure: .

3. NO releasing molecule of claim 1, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 45ºC.

4. The thermo-responsive hydroxylamine NO releasing molecule of claim 1, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO above a temperature of 100ºC.

5. The thermo-responsive hydroxylamine NO releasing molecule of claim 1, wherein the thermo-responsive hydroxylamine NO releasing molecule releases NO within a temperature range of 45 ºC to 300ºC.

6. An amorphous solid dispersion comprising the thermo-responsive hydroxylamine NO releasing molecule of claim 1, within a porous matrix.

7. The amorphous solid dispersion of claim 6, wherein the NO releasing molecule is covalently bound to the porous matrix.

8. The amorphous solid dispersion of claim 6, wherein the NO releasing molecule is non- covalently bound to the porous matrix.

9. The amorphous solid dispersion of claim 6, wherein the porous matrix comprises a polymer, lipid, inorganic oxide, alumina, or resin.

10. The amorphous solid dispersion of claim 6, wherein the porous matrix comprises a neutral organic polymer.

11. The amorphous solid dispersion of claim 6, wherein the porous matrix comprises a cross-linked polystyrene matrix, a hyper-crosslinked polymer, a porous aromatic framework, a porous organic polymer, a conjugated microporous polymer, and/or a covalent organic framework.

12. The amorphous solid dispersion of claim 11, wherein the hyper-crosslinked polymer comprises HCP-1 or HCP-1-OEt.

13. The amorphous solid dispersion of claim 12, wherein the HCP-1-OEt has been pre- treated with NaOEt.

14. The amorphous solid dispersion of claim 9, wherein the polymer comprises PAF-1, PIM- 1, or polystyrene.

15. The amorphous solid dispersion of claim 9, wherein the resin comprises trityl chloride resin, 2-Chlorotrityl chloride resin, DHPP, MBHA, 4-methyltrityl chloride resin, 4-methoxytrityl chloride resin, Hydroxy-(2-chorophnyl)methyl-PS, Rink Acid Resin, Wang resin, or hydroxymethyl phenoxymethyl polystyrene (HMP) resin.

16. The amorphous solid dispersion of claim 9, wherein the resin comprises trityl chloride resin.

17. The amorphous solid dispersion of claim 6, wherein the porous matrix has a pore size of 0.5-5 nm.

18. A method of releasing inhalable nitric oxide (NO) from the hydroxylamine NO releasing molecule of claim 1, the method comprising applying heat to the hydroxylamine NO releasing molecule.

19. The method of claim 18, wherein the applying heat comprises actuating an inhalant device comprising a heating element.

20. The method of claim 18, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of at least 45ºC.

21. The method of claim 18, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of at least 100ºC.

22. The method of claim 18, wherein the heat is applied so that the thermo-responsive hydroxylamine NO releasing molecule reaches a temperature of between 45ºC and 220ºC.

23. An inhaler comprising the hydroxylamine NO releasing molecule of claim 1.

24. The inhaler of claim 23, wherein the inhaler is a vaporization device.

25. A method comprising inhaling NO released from the hydroxylamine NO releasing molecule of claim 1.

26. The method of claim 25, wherein the method does not include inhaling NO2 with the NO.

27. A method of synthesizing trityl-diphenyloxazine comprising: combining trityl chloride of formula of formula of formula .

28. hydroxylamine nitric oxide (NO) releasing molecule of claim 1 in the treatment of pulmonary conditions.

29. The use of claim 28, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma.

30. Use of the amorphous solid dispersion of claim 6 in the treatment of pulmonary conditions.

31. Use of the amorphous solid dispersion of claim 30, wherein the pulmonary conditions are pulmonary hypertension, acute pulmonary vasoconstriction, respiratory distress syndrome, pulmonary edema, sepsis, Covid-19, cystic fibrosis-associated lung infections, sickle cell disease, and asthma.

32. An inhalation device for delivery of inhaled NO from the thermo-responsive hydroxylamine nitric oxide (NO) releasing molecule of claim 1, the inhalation device comprising: a gas intake through which a carrier gas is introduced into the inhalation device; an outlet through which NO is released; an NO generator comprising a heating element positioned between the intake and the outlet; an NO sensor; and an NO2 sensor, wherein feedback from the NO sensor and the NO2 sensor regulates an amount of NO generated by the NO generator.