CN102850403B - Water-soluble iron carbonyl compound, and preparation method and application thereof - Google Patents
Water-soluble iron carbonyl compound, and preparation method and application thereof Download PDFInfo
- Publication number
- CN102850403B CN102850403B CN201210175853.XA CN201210175853A CN102850403B CN 102850403 B CN102850403 B CN 102850403B CN 201210175853 A CN201210175853 A CN 201210175853A CN 102850403 B CN102850403 B CN 102850403B
- Authority
- CN
- China
- Prior art keywords
- compound
- preparation
- mercaptoethylamine
- reaction
- releasing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a water-soluble iron carbonyl compound, and a preparation method and an application thereof. The compound has a structural formula represented by the formula (1). When the compound is subjected to a reaction with mercaptoethylamine, CO can be released. The compound provided by the invention has good water solubility and appropriate stability. Metal ions and organic ligands involved in the reaction have good biocompatibility. Residual substances after CO releasing are harmless or slightly toxic to bodies. The timing and rate of CO releasing are easy to control.
Description
Technical field
The present invention relates to technical field of medical chemistry, be specifically related to a kind of water-soluble iron carbonyl compound and preparation method thereof and the application in carbon monoxide controllable release.
Background technology
Carbon monoxide (CO) is a kind of well-known poisonous gas, but research shows that it is the same with nitrogen protoxide (NO), be a kind of important messenger molecule in body, there is the multiple physiological role such as vasodilator and bronchial smooth muscle, anticoagulant, inflammation-inhibiting reaction, anti-oxidant, anti-apoptotic, antiproliferative in vivo; In the physiological processs such as nerve, breathing, circulation and suppress also to play important regulative in the pathologic process such as acute lung injury, internal organs ischemical reperfusion injury, organ transplant rejection.
The shortcoming of direct suction CO gas is apparent: the CO of suction has to pass through whole respiratory system, then arrives at related tissue through blood circulation, and this is inappropriate for the situation that only need locally play a role; Concentration and dosage wayward; Simultaneously this method also has and causes patient and medical worker surprisingly to suck high dosage CO and poisoning risk.
Transition metal carbonyl compound is a metalloid-organic compound, and carbonyl (CO) wherein can be left away, as illumination, substitution reaction, redox induction etc. under suitable condition.Utilize these character of metal carbonyl to design, synthesize some specific transition metal carbonyl compounds, make it to discharge CO under suitable conditions, i.e. carbon monoxide emitter (molecule) (carbon monoxide-releasing molecules, CORM).CO is provided both without the need to by organism metabolism process through local application, also without the need to through respiratory system with CORM; Consumption size, medication time and release rate easily control, simultaneously also safer relative to directly sucking CO.
Animal model test result shows to have fabulous application prospect based on the CORM of metal carbonyl.Up to the present, the metal carbonyl CORM of report is mainly based on metallic elements such as Ru, Mn, Mo, but some metals such as Ru, Mo etc. are not that organism must element in these compounds, majority of compounds also ubiquity stability or poorly water-soluble and the problem such as rate of release is improper in addition.Therefore, research has good water-soluble and appropriate stability, and discharge the residual substance after CO to body harmless CORM has independent intellectual property right to exploitation, hypotoxic CORM new drug is of practical significance.
Iron is the essential element of many organisms, organism has complete metabolic mechanism to it, therefore, carbon monoxide emitter (CORM) based on iron molybdenum cofactor may have less toxicity or not have toxicity, but also fewer based on the report of iron molybdenum cofactor CORM at present.And these compounds part used such as cyclopentadiene and pyrone and derivative ligand, acyloxy cyclohexadiene etc. are not common are machine molecule in organism, its meta-bolites may produce detrimentally affect to body.
The traditional method of current synthesis carbon monoxide emitter is react by part and metal ion the metal complexes being assembled into and can discharging carbon monoxide, the part cycle needed for this kind of compou nd synthesis reaction is longer, assemble the metal complexes with appropriate stability in addition further and have great difficulty again, because compound is too stable, not easily discharge carbon monoxide, compound is too unstable to be not easy again to obtain in synthesis.Therefore study the CORM of biocompatible metal ion and part, and a kind of method finding suitable release carbon monoxide is of great significance with regard to tool.
Summary of the invention
The invention provides a kind of compound discharging carbon monoxide, this compound has good water-soluble and appropriate stability, metal ion involved by reaction and organic ligand also all have good bio-compatibility, and the residual substance after release CO is harmless or toxicity is less to body.
A kind of compound, its structural formula is such as formula shown in (1):
Described compound has following three kinds of isomerss:
Above-mentioned three kinds of isomerss all can react with mercaptoethylamine and generate CO, reach the object of slow controllable release C0.
Present invention also offers the preparation method of described compound, comprising:
By Fe
3(CO)
12be dissolved in organic solvent with 1-mercapto glycerol, lower than 120 DEG C, preferably react under the condition of 60 ~ 80 DEG C, take on a red color to reaction solution, separation and purification obtains described compound, and concrete reaction process as shown in Figure 1.
Organic solvent is by stock dispersion in same reaction system, and be preferably tetrahydrofuran (THF), tetrahydrofuran (THF) is the aprotic solvent of middle polarity, and each component in it and reaction system does not react, and molecular weight, be easy to and product separation.
Suitable material rate contributes to the abundant reaction of raw material and the generation of product, preferably, and described Fe
3(CO)
12be 1:1 ~ 2:7 with the mol ratio of 1-mercapto glycerol.
Reaction times is too short, and reaction can not fully be carried out, and the reaction times is preferably 1 ~ 4 hour.
The process of separation and purification, mainly by solvent and the removing of unreacted raw material, is preferably: first remove the organic solvent in reaction solution by rotary evaporation, then carry out recrystallization to Red oil product, the method is simple to operate, and can keep product stable.
Invention further provides the application of described compound in slowly-releasing CO.
A method of slowly-releasing CO, comprising: be dissolved in methyl-sulphoxide by described compound, adds the mercaptoethylamine aqueous solution.
Preferably, described compound is dissolved in the concentration in methyl-sulphoxide is 0.001mol/L ~ 0.02mol/L.
The add-on of mercaptoethylamine affects the release rate of CO, and add-on is larger, and release rate is faster, and preferably, the concentration of the described mercaptoethylamine aqueous solution is 4 ~ 5mol/L, and add-on is 10 ~ 120 μ L.
Compared with prior art, the beneficial effect of the compounds of this invention is:
(1) this compound has the stability of good water-based and appropriateness;
(2) metal ion involved by this compound and organic ligand have good bio-compatibility;
(3) this compound release opportunity of carbon monoxide and speed are easily controlled.
Accompanying drawing explanation
Fig. 1 is the compounds of this invention 1 reacting flow chart.
Fig. 2 is the infrared spectrogram of compound 1.
Fig. 3 is the nucleus magnetic resonance figure (containing compound 1 three kinds of isomer) of compound 1; Wherein Fig. 3 a and Fig. 3 b is the nuclear magnetic resonance map of compound 1 prepared by different time, and Fig. 3 c is for having added D
2the nuclear magnetic resonance map of the compound 1 after O.
Fig. 4 is two kinds of infrared figure of product after compound 1 adds mercaptoethylamine.
Fig. 5 is the infrared variation diagram adding compound 1 after 6eq mercaptoethylamine; Wherein, (a) is for adding the infrared variation diagram of 0 ~ 25min compound 1 after mercaptoethylamine; B () is for adding the infrared variation diagram of 45 ~ 175min compound 1 after mercaptoethylamine.
Embodiment
1, the preparation of compound
2.81g Fe is added in tetrahydrofuran (THF) (THF)
3(CO)
12with 0.94g 1-mercapto glycerol, in 70 DEG C of reaction 2h, obtain red solution, rotary evaporation removing solvent (THF) wherein, then recrystallization is carried out to Red oil product, the solvent used is methylene dichloride/hexanaphthene mixed solvent, final obtained pure Red oil material, temporary called after compound 1.
2, the sign of compound
Utilize Varian Scimitar 600 to gather the infrared spectrogram of compound 1, as shown in Figure 2, compound 1 is at 3367cm
-1(OH stretching vibration), 2876,2928cm
-1(CH
2stretching vibration), 1415cm
-1(CH
2flexural vibration), 1992 ~ 2073cm
-1(C=O stretching vibration), 1262 ~ 1334cm
-1(OH in-plane bending), 561 ~ 617cm
-1(OH out-of-plane bending), 1031 ~ 1071cm
-1(C-O stretching vibration) has obvious absorption peak, can confirm in compound 1 containing OH, CH
2, C=O and C-O structure.
Fig. 3 is the nuclear magnetic resonance map of compound 1, and it contains the structural information of three kinds of isomer, and the structural formula of three kinds of isomerss is:
In compound 1, bridging mercapto glycerol deposits three kinds of configurations, and two cis (aa), along one anti-(ae), two trans (ee), are symmetrical structures at the compound of ligand moiety aa configuration,
1in HNMR, OH has two kinds of peaks to exist, and be double peak and triplet respectively, ae configuration has four kinds of peaks, be two double peaks and two triplets respectively, ee configuration is also symmetrical structure, has two kinds of peaks to exist too, double peak and triplet respectively, so the ratio of double peak and triplet is 1:1.
The ratio equally can releasing O-H and C-H from structural formula is 2:5, four kinds of double peaks and two kinds of quintets are had according to the known compound of Fig. 3 a and 3b 1, two quintets are coupled by four triplets to obtain, the ratio of double peak and quintet is 1:1, because Fig. 3 a and 3b prepares at different time, environmentally having, the ratio of subtle difference therefore three kinds of isomer is different.When adding a D in the compound of 3b
2during O, nuclear-magnetism becomes Fig. 3 c, and OH peak disappears, and water peak also moves simultaneously, and the ratio that composition graphs 3b calculates O-H and C-H is 7.38:19.68 ≈ 2:5.
3, the application of compound
By the compound 1 (17mg of preparation, 34mmol) add 3mL DMSO, add after dissolving in reaction tubes, add 20 (3eq), 40 (6eq), 80 (12eq) μ L mercaptoethylamine (1g/2.5ml) aqueous solution at 37 DEG C respectively, survey at set intervals once infrared (Varian Scimitar 600).
Add mercaptoethylamine in compound 1 after, infrared spectrum generation considerable change, as shown in Figure 4, compound 1, product 1 and product 2 are respectively at 2068,2031,1989cm
-1(three); 2015,1974,1942,1907cm
-1(four); 2004,1941cm
-1(two) have obvious carbonyl absorption peak, illustrate that it is respectively six carbonyls, pentacarbonyl and dicarbonyl compound.It can thus be appreciated that compound 1 carbonyl after adding mercaptoethylamine reduces gradually and discharges as carbon monoxide, illustrate that this process can discharge carbon monoxide.
As shown in Fig. 5 (a), compound 1 six carbonyl peaks after adding mercaptoethylamine weaken gradually, and pentacarbonyl peak strengthens gradually, illustrate that namely compound gradates as product 1, has carbonyl to leave away in this process, namely has carbon monoxide to discharge; As shown in Fig. 5 (b), along with time variations pentacarbonyl peak weakens gradually, dicarbapentaborane peak strengthens gradually, illustrates that product 1 gradates as product 2, has carbonyl to leave away, namely have carbon monoxide to discharge in this process.
Table 1 compound 1 discharges the transformation period of carbon monoxide under mercaptoethylamine different ratios
| Compound 1 transformation period | 3eq mercaptoethylamine | 6eq mercaptoethylamine | 12eq mercaptoethylamine |
| t 1/2(min) | 62 | 7.1 | 4.4 |
As can be seen from Table 1, the speed that compound 1 discharges carbon monoxide is relevant with the amount of mercaptoethylamine, and namely along with the amount of mercaptoethylamine increases, speed of reaction is obviously accelerated.The speed of this compound release carbon monoxide can regulate as required as can be seen here.
Claims (10)
1. a compound, is characterized in that, structural formula is such as formula shown in (1):
2. a preparation method for compound as claimed in claim 1, comprising:
By Fe
3(CO)
12be dissolved in organic solvent with 1-mercapto glycerol, react under lower than the condition of 120 DEG C, take on a red color to reaction solution, separation and purification obtains described compound.
3. preparation method as claimed in claim 2, it is characterized in that, described organic solvent is tetrahydrofuran (THF).
4. preparation method as claimed in claim 2, is characterized in that, Fe
3(CO)
12be 1:2 ~ 2:3 with the mol ratio of 1-mercapto glycerol.
5. preparation method as claimed in claim 2, it is characterized in that, the reaction times is 1 ~ 4 hour.
6. preparation method as claimed in claim 2, it is characterized in that, the method for described separation and purification is: rotary evaporation removes the organic solvent in reaction solution, then carries out recrystallization to Red oil product.
7. the application of compound in slowly-releasing CO as claimed in claim 1.
8. a method of slowly-releasing CO, comprising:
Compound according to claim 1 is dissolved in dimethyl sulfoxide (DMSO), adds the mercaptoethylamine aqueous solution.
9. method as claimed in claim 8, it is characterized in that, the described compound concentration be dissolved in methyl-sulphoxide is 0.001 ~ 0.02mol/L.
10. method as claimed in claim 8, it is characterized in that, the concentration of the described mercaptoethylamine aqueous solution is 4 ~ 5mol/L, and add-on is 10 ~ 120 μ L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210175853.XA CN102850403B (en) | 2012-05-29 | 2012-05-29 | Water-soluble iron carbonyl compound, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210175853.XA CN102850403B (en) | 2012-05-29 | 2012-05-29 | Water-soluble iron carbonyl compound, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102850403A CN102850403A (en) | 2013-01-02 |
| CN102850403B true CN102850403B (en) | 2015-01-14 |
Family
ID=47397430
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210175853.XA Expired - Fee Related CN102850403B (en) | 2012-05-29 | 2012-05-29 | Water-soluble iron carbonyl compound, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102850403B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104814952B (en) * | 2015-04-16 | 2017-12-26 | 嘉兴学院 | A kind of method for promoting carbon monoxide emitter release carbon monoxide and preventing from being formed precipitation |
| CN109134551B (en) * | 2018-06-15 | 2021-01-05 | 嘉兴学院 | Water-soluble iron carbonyl compound and preparation method and application thereof |
| CN110078628B (en) * | 2019-04-03 | 2022-02-15 | 嘉兴学院 | Water-soluble iron-based carbon monoxide releasing agent and preparation method and application thereof |
| CN112920225B (en) * | 2021-01-26 | 2024-04-12 | 嘉兴学院 | Sulfonate-containing water-soluble iron carbonyl compound and preparation method and application thereof |
| CN113943327B (en) * | 2021-10-26 | 2023-06-20 | 嘉兴学院 | Azadiene iron carbonyl compound, preparation and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1646140A (en) * | 2002-02-04 | 2005-07-27 | 阿尔法玛药品研发有限公司 | Use of a compound having the ability to release CO in preparation of pharmaceutical compositions for treatment of inflammation |
| DE102010014411A1 (en) * | 2010-04-08 | 2011-10-13 | Friedrich-Schiller-Universität Jena | New iron complexes, useful as carbon monoxide and iron releasing molecules for treating e.g. high blood pressure, cancer, tissue damage by irradiation, post-ischemic injury, atherosclerosis, sepsis, angina and myocardial infarction |
| DE102010014412A1 (en) * | 2010-04-08 | 2012-04-19 | Friedrich-Schiller-Universität Jena | Use of dinuclear iron complexes having sulfur-containing ligands as carbon monoxide-releasing pharmacological agents e.g. for treating hypertension, cancer, tissue damage by irradiation, post-ischemic injury, atherosclerosis or sepsis |
-
2012
- 2012-05-29 CN CN201210175853.XA patent/CN102850403B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1646140A (en) * | 2002-02-04 | 2005-07-27 | 阿尔法玛药品研发有限公司 | Use of a compound having the ability to release CO in preparation of pharmaceutical compositions for treatment of inflammation |
| DE102010014411A1 (en) * | 2010-04-08 | 2011-10-13 | Friedrich-Schiller-Universität Jena | New iron complexes, useful as carbon monoxide and iron releasing molecules for treating e.g. high blood pressure, cancer, tissue damage by irradiation, post-ischemic injury, atherosclerosis, sepsis, angina and myocardial infarction |
| DE102010014412A1 (en) * | 2010-04-08 | 2012-04-19 | Friedrich-Schiller-Universität Jena | Use of dinuclear iron complexes having sulfur-containing ligands as carbon monoxide-releasing pharmacological agents e.g. for treating hypertension, cancer, tissue damage by irradiation, post-ischemic injury, atherosclerosis or sepsis |
Non-Patent Citations (2)
| Title |
|---|
| Graeme Hogarth等,.γ-Hydroxypropyl-functionalised iron thiolate complexes: crystal and molecular structure of [{Fe2(CO)6(l-SCH2CH2CH2OH)}2-(μ4-S)].《Transition Met Chem》.2008,第33卷第729-732页. * |
| Jean-Franc¸ois Capon等,.Electrochemical and theoretical investigations of the reduction of [Fe2(CO)5L{l-SCH2XCH2S}] complexes related to [FeFe] hydrogenase.《New Journal of Chemistry》.2007,第31卷第2052-2064页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102850403A (en) | 2013-01-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102850403B (en) | Water-soluble iron carbonyl compound, and preparation method and application thereof | |
| DE69531795T2 (en) | BETA, BETA'-DIHYDROXY MESO-SUBSTITUTED CHLORINE, ISOBACTERIOCHLORINE AND BACTERIOCHLORINE AND METHOD FOR THE PRODUCTION THEREOF FROM BETA, BETA'-UNSubstituted TETRAPYROLIC MACROCYCLES | |
| DE69834923T2 (en) | HIGH GRADE LIPOPHILIC CAMPTOTHECINE DERIVATIVES | |
| CN108030921B (en) | Preparation method and application of albumin-loaded metalloporphyrin complex nanoparticles | |
| CN107163166B (en) | Preparation method of chitosan-citric acid-rare earth complex | |
| DE60311456T2 (en) | METHOD FOR PRODUCING IRON HYDROXYPYRONE COMPOUNDS | |
| Li et al. | A straightforward access to trifluoromethylated natural products through late-stage functionalization | |
| JP2001527077A (en) | Metal corinoids as biologically compatible carriers for pharmacological agents | |
| RU2014132184A (en) | KALMANGAFODIPIR, NEW CHEMICAL COMPOUND AND OTHER MIXED COMPLEX COMPOUNDS WITH METALS, METHODS FOR PRODUCING, COMPOSITIONS AND METHODS OF TREATMENT | |
| CN111732608B (en) | Phenanthroline-based manganese carbonyl compound, preparation method and application | |
| CN100420689C (en) | Porphyrin derivate with macrosubstituent, preparation process thereof and use as small molecule antioxidant | |
| CN111728981A (en) | Quercetin rare earth complex and preparation method thereof | |
| CN102286279A (en) | Benzene derivative metal ion fluorescent probe and use thereof | |
| CN115368430B (en) | Preparation method and application of tripterine metal complex | |
| CN106620714A (en) | 7-ethyl-10-hydroxycamptothecine-polymer conjugated drug and preparation method of drug nano-preparation | |
| CN104814952B (en) | A kind of method for promoting carbon monoxide emitter release carbon monoxide and preventing from being formed precipitation | |
| CN109134551A (en) | Water-soluble iron carbonyl complex and its preparation method and application | |
| CN111303216B (en) | Preparation method and application of metal organic ternary cyclic compound | |
| CN110078628B (en) | Water-soluble iron-based carbon monoxide releasing agent and preparation method and application thereof | |
| Hassan et al. | Synthesis and characterization of benzohydroxamic acid metal complexes and their cytotoxicity study | |
| CN112920225B (en) | Sulfonate-containing water-soluble iron carbonyl compound and preparation method and application thereof | |
| CN105801626B (en) | A kind of water soluble pegylation Fischer carbene compounds and preparation method thereof | |
| Howell et al. | Thermal degradation of platinum (IV) precursors to antitumor drugs | |
| CN113620964A (en) | Substituted calixazole derivatives, and synthetic method and application thereof | |
| Chohan | Symmetric 1, 1′‐Dimethylferrocene‐Derived Amino Acids: Their Synthesis, Characterization, Ligational and Biological Properties With Cu (II), Co (II) and Ni (II) Ions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150114 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |