WO2009079408A1

WO2009079408A1 - Biologically active polymeric compounds, their methods of production and uses thereof

Info

Publication number: WO2009079408A1
Application number: PCT/US2008/086688
Authority: WO
Inventors: Paul M. Puckett; Mark Livesay
Original assignee: Sunrez Corporation
Priority date: 2007-12-14
Filing date: 2008-12-12
Publication date: 2009-06-25

Abstract

Described herein are biologically active compounds, methods for making such compounds, wherein said methods comprise reacting a phenolic residue with an amine to form an biologically active polymeric material

Description

BIOLOGICALLY ACTIVE POLYMERIC COMPOUNDS, THEIR METHODS OF PRODUCTION AND USES THEREOF

FIELD OF THE SUBJECT MATTER The present subject matter relates to, biologically active polymeric compounds, their methods of production and uses thereof.

BACKGROUND OF THE SUBJECT MATTER

At some level, most materials whether naturally occurring or synthetically produced provide the essential resources for sustaining life, that is they function as either shelter or food for living organisms.and sometimes both. Biological encroachment occurs when different species compete for these life-sustaining resources. Encroachment runs the gamut from simple competition to parasitism with symbiotic relationships being cooperative instead. From a human-centric view point, this struggle versus microorganisms is manifested in numerous ways in everyday life including: a) spoilage of food items whether it occurs in refrigerators or in grain silos; b) discoloration of surfaces whether shower stalls or building exteriors including paints, wood and wood products, gypsum, plaster, stucco, tiles, bricks, masonry and concrete; c) infection of the skin, including athletes foot, acne, impetigo, seborrheic dermatitis, gangrene, pityriasis, boils, carbuncles, etc.; d) (bio)fouling of fuel lines and filters in diesel engines, or membranes and pipes for aqueous systems (microfouling); and e) (bio)corrosion of metallic structures underlying "protective coatings".

These problems are very often the result of uncontrolled growth of bacteria, fungus (e.g. mildew, mold, yeast), or algae on surfaces that possess the right combination of conditions, such as the right amount of light, a suitable temperature, appropriate humidity levels or a combination thereof. The feeding, growth, and elimination from microorganisms are often accompanied by the release of noxious odors and/or toxins as well as acidic or basic waste products. As one moves up the biological scale from unicellular to multicellular life, encroachment remains a major economic, medical, and social problem with some limited examples from a human- centric viewpoint including: a) macrofouling or attachment and growth on boat bottoms, piers, docks, pipelines and gratings by barnacles, mussels, polychaete worms, bryozoans, and seaweed; b) destruction of property such as a wood frame houses and crops from termite (Isoptera) infestation, interestingly it is actually a symbiotic pairing of protozoa (Tήchonympha) and bacteria in the termites gut that digests the cellulose of the wood; and c) itching and inflammation of skin from hematophagous life forms such as bedbugs (Family Cimicidae; Cimex lectυlaήus), mites (Acarina), chiggers (genus Trombicula are the larval stage of Harvest mites), ticks (Ixodesi), triatoma, blood -sucking flies and midges (Dipteran - like sandflies {Ceratopogonidae) , Tsetse fly (Glossinidae), mosquitoes (Culicidae)), fleas (Siphonaptera), and lice {Pediculυs and Phthiraptera) which can and often do lead to the introduction of internal parasitic microorganisms like protozoa, bacteria, viruses and nematodes.

A conventional solution to this problem of micro and multicellular organisms encroaching is the introduction of chemicals into an area to repel or kill them. This solution was not invented by humans, but has naturally-occurring precedence. As an example, many plants in their evolutionary attempt to deal with encroachment of other species developed the ability to produce phytochemicals which act as repellents against other plant or animal aggressors. In the modern world of synthetic materials, it is possible to add toxic chemicals to a surface, or place them in a material and allow them to leach out through the surface over time, killing the organisms and removing the problem. Examples of this classical approach to dealing with unwanted organisms via leachable toxins are the use of copper or tin in bottom paint for boats, wall paints and coatings containing fungicides and mildewcides, and the use of Triclosan and Nisin in thermoplastic toys and cutting boards. In, recent years this approach has also been extended to use of quaternary ammonium salts or colloidal silver in textiles for clothing, outdoor gear, tents and shelters. Microban (quats and silver) and Haloshield (halogens) have introduced commercial technologies that provide anti-microbial activity to a variety of substances - from textiles to paints. Dow Corning has also developed a method of binding quaternary ammonium salts to polymer surfaces; typically textile polymers, using their silane technology. Lysol (Reckitt Benckiser) has also described a method of attaching ortho-phenylphenol to an acrylate polymer through a quaternary ammonium salt.

An "antibiotic" is a chemical compound that inhibits or completely stops the growth of microorganisms, such as bacteria, fungi, or protozoans. Originally the meaning of antibiotic included an agent with biological activity against any living organism (single or multicellular); however, the term is now more commonly used to describe substances with anti-bacterial, anti-fungal, or anti-protozoal activity.

Bacteriostatic antibiotics hamper the growth of bacteria by interfering with bacterial - protein production, DNA replication, and cellular metabolism. Bacteriostatic antibiotics inhibit growth and reproduction of bacteria without killing them; killing is done by bactericidal agents. However, as often occurs, it is a dose dependent function. There is not always a precise distinction.between bacteriostatic and bactericides; high concentrations of most bacteriostatic agents are also bactericidal, whereas low concentrations of bacteriocidal agents are typically only bacteriostatic. These distinctions of -static and -cidal hold true across a range of organism descriptions whether bacteria, fungi, protozoa, nematodes etc. Functional effects of microbial stasis are equivalent to microbiocidal activity, since inhibition of the growth and reproduction processes in micro-organisms are sufficient to stop the adverse effects of the microbes. This is because the problems associated with microbes are generated by large growing and thriving colonies of microbes and/or the wastes they are producing. The compounds that are routinely used as toxins have several things in common. They are all active against the target microorganism, and they are all relatively low molecular weight molecules, and can therefore be easily transported in fluid media, and absorbed onto the surface or into (crossing through protective cellular membranes) a microorganism where they stop some vital function necessary for life. These compounds can be chosen from inorganic or organic materials. They include inorganics such as silver, copper, tin, arsenic, selenium, mercury metals and salts, iodine, chlorine, permanganate, borates, and a very old and thoroughly tested preservative sodium chloride. There are also many oxidizers used as anti-microbials including simple compounds like hydrogen peroxide as well as peroxy compounds of borates, phosphates, sulfates, and organic acids and esters like benzoates and acetates. Another common type of oxidizer that is widely used is bleach, specifically hypochlorites. Sodium hypochlorite is household bleach and calcium hypochlorite for many decades has been the standard disinfectant used in swimming pools.

Using teachable toxins to combat unwanted microbes or multi-cellular organisms in a terrestrial or marine environment has several fundamental disadvantages. First, once the toxins have substantially leached from the protected surface, the surface ceases to be protected. A further issue is releasing the toxins into the environment, where it is possible and even probable that the toxin will interact with non-targeted life-forms with unintended consequences and cause damage to a local ecosystem. An excellent example of this effect is the observed problems with the build up of copper and tin from bottom paints which accretes in bays and estuaries, causing problems with other non-targeted organisms. Another approach to developing antimicrobials is the use of small and reactive organics, including phenols and quaternary ammonium salts which have their origin in medical history. In the mid-1800's Louis Pasteur and Joseph Lister dramatically improved the quality of life for everyone that came after them. Pasteur advanced the "germ theory" of disease and his friend Lister instituted the use of antiseptic procedures in the operating room. At that point in history almost 50% of the patients undergoing major surgery died, not from the operation but primarily from infection by pathogenic bacteria. The problem had its origin in cross contamination from the operating table, surgeon's instruments, or the hair, clothing, or skin of the physician himself. Lister began using carbolic acid (phenol) and later boric acid, to kill the germs in the operating room and to treat patient's bandages to prevent infection. Even with all the advances of the last 150 years of microbial research, and with our much greater understanding of the cause and preventatives for these problems, the development of secondary infections by patients in medical facilities is still a deadly serious issue, causing approximately 90,000 deaths annually in the US. In modern medical facilities, homes and offices, solutions containing phenol and phenolic compounds like nonylphenol and triclosan, or quaternary ammonium salts, are still used to combat the problems associated with microbes. Pasteur is probably best known for the "pasteurization" process by which harmful microbes in perishable food products are destroyed using heat, without destroying the food. Even now after a century of advancement, over 95% of all food "poisoning" is caused by microbial contamination of food The FDA has estimated that there are 25 to 100 million cases of food poisoning annually, resulting in as many as 10,000 deaths. Estimates are used because in most cases, the symptoms are of short duration and' considered neither severe nor unusual enough to seek medical attention - and therefore go unreported. When instances of food poisoning occur at home or in commercial operations, these tend to be associated not with poorly prepared (cooked) food, but with cross-contamination from pathogens originally harbored in uncooked foods. This cross-contamination arises from a variety of sources including contaminated rags, utensils and improperly cleaned food preparation sites like sinks and counter tops, and especially porous surfaces like wood, grout, and some plastic materials. From ancient times to the modern world, additives have been used to prevent or slow microbial contamination associated with food preparation and storage. Food preservation with salt, sugar, smoking, and pickling (high acid content - low pH) are well known, and are now understood on the level of chemical interactions with microorganisms. Many modern food additives - benzoates, sorbates, propionates, have their basis in natural products and processes. For centuries, spices have been used as food preservatives. The antibiotic activity of spices is generally linked to one or two chemicals, usually volatile oils, within the spice. Many of these oils are classified by relevant controlling agencies as "generally regarded as safe" (GRAS)₁ and are currently allowed for use as flavoring agents in foods. These antimicrobial phytochemicals (chemicals derived from plants) share many chemical similarities. In fact, many share the same phenolic component and differ from each other only in aromatic hydroxyl content and the length of a side chain from the phenol.

Some of the disadvantages associated with these approaches include the lack of control over the rate of release, the eventual loss of all activity, and the release of highly active and toxic compounds into the environment. Without entering the world of internal medicine where antibiotics are a scientific art form, there are in daily life many occasions where it is desirable to kill (micro)organιsms by addition of toxins, these include antibacterial and antifungal soaps, creams, lotions, and powders used on people, pets, and livestock. There are in addition wide assortments of materials used as antimicrobial agents added to soaps, detergents, and cleansers, for bathrooms, kitchens, and in the laundry. There are even antimicrobial agents that are added to diesel fuel to prevent the unwanted effects of these pests in the operation of diesel engines.

Accordingly, there is a need for a composition that is effective in neutralizing negative aspects of encroachment for selected biological species including unicellular and multicellular species. There is a further need for a composition that is non-toxic to humans, animals and the environment, non-corrosive to most materials and can be produced at a near neutral pH (=7 +/- 1). Additionally, there is a need for a composition that may be deployed in large quantities that rapidly and effectively neutralizes the negative and harmful aspects of encroachment of selected biological species.

BRIEF DESCRIPTION OF THE FIGURES

Exemplary embodiments are illustrated in referenced figures. It is intended that the embodiments and figures disclosed herein are to be considered illustrative rather than restrictive.

Figure 1 illustrates a reaction scheme for producing an amine-containing monomer by reduction, in accordance with an embodiment of the present subject matter.

Figure 2 illustrates a reaction scheme for producing an amine-containing monomer by reduction, in accordance with an embodiment of the present subject matter. Figure 3 illustrates a reaction scheme for producing an amine-containing monomer by heat, in accordance with an embodiment of the present subject matter.

Figure 4 illustrates a reaction scheme for producing an amine-containing monomer by heat, in accordance with an embodiment of the present subject matter.

Figure 5 illustrates a reaction scheme for producing an amine-containing monomer by reduction, in accordance with an embodiment of the present subject matter. Figure 6 illustrates a reaction scheme for producing a biologically active monomelic compound when reacted¹ with an epoxy, in accordance with an embodiment of ^"the present subject matter.

Figure 7 illustrates a reaction scheme for producing a biologically active monomelic compound when reacted with an epoxy, in accordance with an embodiment of the present subject matter.

DETAILED DESCRIPTION OF THE SUBJECT MATTER All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present subject matter. It is not an admission that any. of the information provided herein is prior art or relevant to the presently claimed subject matter, or that any publication specifically or implicitly referenced is prior art. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this subject matter belongs. Singleton et a/., Dictionary of Microbiology and Molecular Biology 3^rd ed., J. Wiley & Sons (New York, NY 2001); March, Advanced Organic Chemistry Reactions, Mechanisms and Stnicture 5^th ed. , J. Wiley & Sons (New York, NY 2001); and Sambrook and Russell, Molecular Cloning: A Laboratory Manual 3rd ed., Cold Spring Harbor Laboratory Press (Cold Spring Harbor, NY 2001), provide one skilled in the art with a general guide to many of the terms used in the present application. One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present subject matter. Indeed, the present subject matter is in no way limited to the methods and materials described. For purposes of the present subject matter, the following terms are defined below.

Phytochemicals, many of which are phenolic in nature, have their evolutionary origin in the advantage they provide the host plant as a repellent against other plant or animal aggressors. Moreover, like many of the smartrdrugs of today, most of these phenols are disguised by the plant with functionality that enhances its delivery to the target organism. Many of these phytochemical agents have their biological activity linked to the surface deactivation of proteins in the cell wall of the target organism. Higher plants (woody plants) have two essential building blocks - cellulose and lignin. Cellulose is a natural polymer of sugar (beta-glucose) and lignin is a biopolymer made from- phenolic fragments. These phenolic fragments are readily available to the plant and are used to produce many of the phytochemicals necessary to stop encroachment.

Phytochemicals by nature are relatively nontoxic to humans and higher life forms, but are known to stop encroachment, by either repelling or killing insects and lower forms of plant and animal life down to the size of microbes. The new materials and processes described in this disclosure can be used to produce a new type of polymer that has biological activity. By judiciously choosing among these naturally- occurring phytochemicals, it is possible to introduce this desirable property into synthetic materials including thermoset and thermoplastic resins coatings, primers, adhesives, and composites.

Thermoset resins have been the dominant materials for production of coatings, primers, adhesives, and composite materials for many years. Some of the commonly used thermoset plastic materials include unsaturated polyester resins, vinyl ester resins, epoxies, (poly)urethanes, phenolics, silanes, alkyds and blends and mixtures of these resins. The reason for the use of these plastic materials in these applications is their intrinsically low viscosity and curing rheology which makes them exceptionally processable. Besides the excellent processability of this class of materials, thermoset resins possess a variety of additional desirable characteristics including excellent adhesion to a variety of substrates, excellent corrosion resistance versus many corrosive environments, excellent mechanical properties including high strength and hardness, and abrasion resistance. Because thermoset resins are low molecular weight materials, which react during the process that forms them into a finished product, they produce a very high molecular weight crosslinked polymer structure that cannot be reformed or reshaped.

Thermoplastic materials have become increasingly popular as matrices for films, surface coatings and some composites. The high molecular weight of thermoplastic materials makes them more difficult to process into finished fabricated forms than thermoset resins, but can also provide advantages-such as exceptional toughness, resistance to corrosive environments, and environmental degradation. Thermoplastic resins also have the advantage that they can be recycled by heating and reshaping or remolding. Because thermoplastics exists as high molecular weight polymers, it is typical that they can be molded very quickly (much faster than thermoset resins) into a finished shape. Some of the commonly used thermoplastic materials include polyethylene (PE), polyethylene grafted maleic anhydride (PE-g- . MA), poly(ethylene^co-methacryϊic acid) (PEMA), poly(ethylene-co-zinc methacrylate) (Suriyn), polypropylene (PP), polypropylene maleic anhydride copolymers (PP-MA), polyvinylchloride (PVC), polyvinyldichloride (PVDC, Saran), polymethylmethacrylate (PMMA), polyamides (PA, nylon), polystyrene (PS), poly(styrene-co-maleic anhydride) (SMA), polyethyleneterephthalate (PET), polybutyleneterephthalate (PBT), and blends and mixtures of these resins.

The present subject matter discloses novel methods and compounds that have been developed and are described herein that are designed to exploit the strong biological activity of these GRAS phytochemical agents in the development of new types of plastics. These new and useful thermoset and thermoplastic polymers are made by modifying a normal polymer's molecular structure by chemically reacting and binding a novel amine-containing compound into the polymer imparting a new bioactivity to the resultant polymer. A strong advantage of this type of bioactive polymer is that the active portion is permanently (chemically) bound to the final high molecular weight polymer, and therefore, does not migrate. In other words, the new polymer's bioactivity is long lasting and does not migrate into the environment or move from the location where it is applied. Specifically, novel biologically active polymeric materials, including plastics, resins, primers, films, adhesives, or coatings, have been developed that will inhibit or completely stop the growth of a wide range of micro and multicellular organisms. The use of these contemplated biologically active polymeric materials as adhesives, primers, films, coatings, fibers, formed plastics or reinforced plastic composite parts derived from either thermoplastic or thermosetting organic resins and inorganic resins, provides surface protection from the negative effects of biological encroachment. Contemplated biologically active polymeric materials are modified so as to mcoφorate at least one type of amine-based compound containing a phenolic residue and if desired additionally, primary, secondary or tertiary amines, quaternary ammonium salts, oximes, hydrazines, hydrazones, (hydro)sulfides, guanidines, pyrolidines, carboxylic acids, carboxylate salts, etc. Some contemplated amine compounds are formed from phenolic phytochemical precursors by reaction with an amine.

Phenolic compounds are ubiquitous in nature, perform a multitude of roles, and provide unique characteristics in biological systems. The hydroxyl of the phenolic unit provides polarity and some water solubility, as well as acting as a weak acid (pKa = 10) in aqueous environments. Lignin, a polymeric phenolic which provides structural support in plants, is produced from three monolignols: coniferyl alcohol, sinapyl alcohol and paracoumaryl alcohol. Lignin is the third most abundant organic compound on earth after cellulose and chitin. When wood (about 30% dry weight lignin) is burned to cook meat it is the phenolic char derivatives of lignin - guaiacol and syringol that provide much of the flavor. Eugenol is a phenolic flavoring agent that has been used for many centuries which is extracted from essential oils (clove, nutmeg, and cinnamon). Vanillin is another phenolic flavoring agent that is extracted from a plant source. The hydrolysable tannins which are produced by numerous plants are derivatives of a sugar and a phenolic, gallic acid. Particularly good sources of hydrolysable tannins are grapes (red wine), cranberries, strawberries, blueberries, and pomegranates which are often consumed for their antioxidant and health benefits.

Salicylic acid is a phenolic compound that serves as a plant hormone and was originally isolated from the bark of willow trees. Chewing on willow bark as a fever reducer has been known since ancient times. Currently, salicylates find their primary uses in skin cremes, aspirin, oil of wintergreen flavoring agents, and bismuth derivatives (Pepto-Bismol). Capsaicin is the phenolic component that provides the hot in chili peppers. Curcumin is a polyphenol that provides the yellow color and peppery taste to turmeric powder (food additive E100) used in mustard and curries. Thyroxine (often abbreviated as T4) is the major phenolic hormone secreted by the thyroid gland that controls metabolic processes in the body. Contemplated phenolic components that may be utilized are water soluble phenolics produced from vanillin, salicylic acid, gallic acid, ethyl vanillin (3-ethoxy-4-hydroxybenzaldehyde), curcumin, salicylaldehyde, and alkyl vanillate.

Contemplated amines that react with these phenolic residues can be any amine, but especially useful amines are those of the amino acids. With the difference in the amino acids that occurs naturally, it is possible to adjust acidity and basicity of the resultant materials and solutions by selection of different combinations of amino acids. Contemplated amino acids include standard amino acids like alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, and non-standard amino acids like gamma-aminobutyric acid, monosodium glutamate (MSG)₁ ornithine, taurine, homocysteine, 4-hydroxyproline, hydroxylysine, sarcosine, beta-alanine, camosine, anserine and aspartame.

Other amines that have been reacted with the phenolic residues to successfully generate novel amine compounds containing phenolic residues are ethylenediamine, diethylenetriamine, triethylenetetramine, bis(hexamethylene)triamine, ethanolamine, diethanolamine, piperazine, aminoethylpiperazine, and polyetherpolyamines (e.g. Jeffamines).

Contemplated biologically active polymeric materials are any suitable molecular weight (molecular mass, MW) depending on the underlying polymers and the application. In some embodiments, these polymeric materials comprise molecular weights greater than 1000. In other embodiments, contemplated polymeric materials comprise molecular weights greater than 10,000. In yet other embodiments, contemplated molecular weights are greater than 100,000. The amount of biologically active phenolic residue that can be incorporated into the polymer can vary widely from as little as 0.1% up to a stoichiometric amount within the finished part. The amount of phenolic residue incorporated into the polymer is determined by its use, chemical qualities, cost-efficiency, and the application.

Contemplated biologically active polymeric materials may be used to modify a surface coating, wherein the coating is designed to inhibit or prevent the implantation of and fouling caused by a barnacles, mussels, polychaete worms, bryozoans, and seaweed, and similar such species on structures found in marine environments. Other contemplated modified surface coatings are those that are used in the storage and filtration of diesel fuel that will inhibit or prevent the micro-fouling caused by microbes. Some contemplated modified surface coatings, particularly primer coatings used on metallic surfaces, are designed to inhibit or prevent the bio- corrosion caused by a microbes growing on the metallic surface and to eliminate microbial waste products that cause metallic corrosion. Other contemplated modified surface coatings are those used on floors, cabinets, shelving, walls, sinks, tubs, and basins in those environments that have some requirement for reduction or elimination of microorganisms such as kitchens, clean rooms, hospitals, abattoirs, etc. In some contemplated embodiments, modified surface coatings can be applied to cement, grout, mortar, concrete, ceramic, gypsum, stucco, tile, brick and similar porous inorganic surfaces which inhibit or prevent microbial growth on these surfaces. Other contemplated modified surface coatings are those which are applied directly to the skin or applied to a plastic or textile surface and then applied to the skin to reduce or eliminate unwanted microbes. In some contemplated embodiments, modified surface coatings can be used with food containers (e.g. bowls, silos) or plastic wraps to reduce the rate of spoilage caused by microorganisms.

In some contemplated embodiments, oils, greases, waxes, salves, ointments, lotions, gels, or creams may be produced with the biologically active polymeric materials disclosed, which may provide protection from the negative effects of biological encroachment on surfaces where a permanent coating is not possible or desirable.

In other embodiments, contemplated biologically active polymeric materials may act as wood, plant or cellulose preservatives, such that when ingested by social insects like termites (Isoptera), the materials will inhibit their growth or kill them, especially because these insects are dependent on the action of gut bacteria to digest and utilize cellulosic foods.

In yet another embodiment, by adjusting the solubility of the biologically active polymeric materials, they can be dispersed or dissolved in water to make an aqueous antimicrobial solution that can be used in a variety of environments, from the home, to medical facilities, to commercial operations that require antiseptic environments. In addition, these solutions can be used as decontaminating solutions to neutralize such compounds as biological warfare agents (BVVA)₁ chemical warfare agents (CWA) or combinations thereof without harming humans. Because there is a unique and selective chemical reaction that occurs between CWA's and biological systems, it is possible to use the new biologically active polymeric materials to selectively react with the CWA's to neutralize these agents rapidly and effectively. These innovative new biologically active polymeric materials, when they are formed as part of thermoplastic resins, can be used much as any other thermoplastic and can be formed and reformed into any typical products, including fibers, films, extruded products like pipes and tubing, and injection molded products, which will inhibit or completely stop the growth of a wide range of microorganisms on those formed products.

Additionally these biologically active polymeric materials can be produced as or incorporated into other materials that are chemically inactive until activated by some triggering mechanism, such as light, temperature, humidity levels or a combination thereof, which allows the polymeric materials to remain inactive until necessary. One example may be heating a surface during sterilization to produce and then maintain a sterile surface.

Thus, specific embodiments and applications of biologically active polymeric materials and their methods of production have been disclosed. It should be apparent, however, to those skilled in the art that many more modifications besides those already described are possible without departing from the inventive concepts herein. The subject matter, therefore, is not to be restricted except in the spirit of the disclosure. Moreover, in interpreting the disclosure, all terms should be interpreted in the broadest possible manner consistent with the context. In particular, the terms "comprises" and "comprising" should be interpreted as referring to elements, components, or steps in a non-exclusive manner, indicating that the referenced elements, components, or steps may be present, or utilized, or combined with other elements, components, or steps that are not expressly referenced.

EXAMPLES The following examples describe a range of applications of the methods of the present subject matter, as well as a number of components that may be readily integrated and/or otherwise used in connection with the same. These Examples demonstrate some of the many steps of the methods of the subject matter, and the potential impact it may have on biological studies and the conventional practice of medicine. Modifications of these EΞxamples will be readily apparent to those skilled in the art.

Example 1

Vanillin (38 grams, 0.25 moles) was dissolved in 100 ml_ of ethanol, and then Glycine (18.8 grams, 0.25 moles) dissolved in 200 ml. of water was added As soon as the Glycine was added the solution turned yellow forming a precipitate in the ethanol/water solvent. Four grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove most of the water and ethanol. The reaction mixture was cooled to O⁰C overnight and 50 grams of crystal product were isolated.

Example 2

Vanillin (30.4 grams, 0.20 moles) was dissolved in 100 mL of ethanol, and then Glycine (7.5 grams, 0.1 moles) dissolved in 100 mL of water was added. As soon as the Glycine was added the solution turned yellow forming a precipitate in the ethanol/water solvent. Three grams of a 5% Pd on. carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove most of the water and ethanol. The reaction mixture was cooled to O⁰C overnight and 33 grams of crystal product were isolated.

Example 3

Vanillin (30.4 grams, 0.20 moles) was dissolved in 100 mL of ethanol, and then Alanine (17.8 grams, 0.20 moles) dissolved in 100 mL of water was added. As soon as the Alanine was added the solution turned yellow forming a precipitate in the ethanol/water solvent. While the reaction was stirring in a 500 mL round bottom flask 4.2 grams of NaHCCb was added, followed by 3.78 grams of NaBH₄ in several aliquots. The reaction mixture was cooled to O⁰C overnight and 41 grams of crystal product were isolated.

Example 4 Vanillin (30.4 grams, 0.20 moles) was dissolved in 100 mL of ethanol, and then Alanine (17.8 grams, 0.20 moles) dissolved in 100 mL of water was added. As soon as the Alanine was added the solution turned yellow forming a precipitate in the ethanol/water solvent. Four grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove most of the water and ethanol. The reaction mixture was cooled to O⁰C overnight and 41 grams of crystal product were isolated.

Example 5

Vanillin (30.4 grams, 0.20 moles) was dissolved in 100 mL of ethanol, and then Alanine (8.9 grams, 0.1 moles) dissolved in 100 mL of water was added. As soon as the Alanine was added the solution turned yellow forming a precipitate in the ethanol/water solvent. Three grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture, was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove most of the water and ethanol. The reaction mixture was cooled to O⁰C overnight and 33 grams of crystal product were isolated.

Example 6

Vanillin (30.4 grams, 0.20 moles) was dissolved in 100 mL of ethanol, and then Alanine (17.8 grams, 0.20 moles) dissolved in, 100 mL of water was added. As soon as the Alanine was added the solution turned yellow forming a precipitate in the ethanol/water solvent. While the reaction was stirring in a 500 mL round bottom flask 4.2 grams of NaHCO₃ was added, followed by 3.78 grams of NaBH₄ in several aliquots. The reaction mixture was cooled to O⁰C overnight and 41 grams of crystal product were isolated Example 7

Vanillin (30.4 grams, 0.20 moles) was dissolved in 120 mL of ethanol, and then MSG (mono sodium glutamate 39.3 grams, 0.21 moles) dissolved in 240 mL of water was added. As soon as the MSG was added the solution turned yellow forming a precipitate in the ethanol/water solvent. To this solution NaHCO₃ (8.4 grams 0.1 moles) was added. Four grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove most of the water and ethanol. The reaction mixture was cooled to O⁰C overnight and 62 grams of crystal product were isolated.

Example 8 Vanillin (38 grams, 0.25 moles) was dissolved in 120 mL of ethanol, and then MSG (mono sodium glutamate 23.4 grams, 0.13 moles) dissolved in 240 mL of water was added. As soon as the MSG was added the solution turned yellow forming a precipitate in the ethanol/water solvent. Four grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove most of the water and ethanol. The reaction mixture was cooled to O⁰C overnight and 51 grams of crystal product were isolated.

Example 9 Vanillin (5.0 grams, 0.033 moles) was dissolved in 15OmL of water and 50 mL of ethanol, along with XTJ-502 polyetheramine (34.7 grams, 0.0165 moles) and 2 grams (0.033 moles) of Acetic Acid. As soon as the reaction mixture was formed it turned cloudy yellow but cleared on continued mixing. Next 1.5 grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove the water and ethanol isolating approximately 60 grams of product. Example 10

The XTJ-502 polyetheramiπe (15.4 grams 0.007 moles) was melted in a microwave and poured into a 250 ml_ round bottom flask along with 20 grams of methylene chloride. As the reaction mixture was stirred Salicylic Acid (1.9 grams 0.014 moles) was added. The flask was attached to the rotary evaporator and the methylene chloride was removed. The flask was then attached to a vacuum pump and the pressure was reduced to 120mm and a heat gun was used to heat the flask until no more bubbles (water evaporation from the liquid) were observed. Approximately 17 grams of the desired amide was isolated.

Example 11

A 500 mL three neck round bottom flask containing 100 ml. of Methanol was stirred while Methyl Salicylate (88.6 grams 0.58 moles) and DETA (diethylene triamine 30 grams 0.29 moles) were added. The reaction flask was fitted with a condenser and a thermometer after all reaction ingredients were added. Upon addition of the DETA the reaction began to heat up to about 5O⁰C. The reaction was heated at about 5O⁰C for an additional 24 hours Following this reaction period the solution is thick with crystal precipitate. The reaction mixture is cooled to less than room temperature and filtered to recover 85 grams of the desired crystal product.. The remaining liquid containing some unreacted DETA and Methyl Salicylate is added to the next reaction which increases the yield on successive reactions to near theoretical.

Example 12 Vanillin (30.4 grams, 0.20 moles) was dissolved in 100 mL of ethanol, and then Serine (10.5 grams, 0.1 moles) dissolved in 100 mL of water was added. As soon as the Serine was added the solution turned yellow forming a precipitate in the ethanol/water solvent. Three grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the, flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then placed on a rotary evaporator to remove most of the water and ethanol. The reaction mixture was cooled to O⁰C overnight and 34 grams of crystal product was isolated. Example 13

Vanillin (38 grams, 0.25 moles) was dissolved in 20OmL of ethanol, along with ethanolamine (16 grams, 0.26 moles) and 15.8 grams<(0.26 moles) of Acetic Acid. As soon as the reaction mixture was formed it turned cloudy yellow but cleared on continued mixing. Next 5 grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then neutralized with NaHCO₃ filtered again, and placed on a rotary evaporator to remove the ethanol isolating approximately 54 grams of thick oily product.

Example 14

Vanillin (36.5 grams, 0.24 moles) was dissolved in 20OmL of ethanol, along with ethanolamine (7.3 grams, 0.12 moles) and 7.2 grams (0.12 moles) of Acetic Acid. As soon as the reaction mixture was formed it turned cloudy yellow but cleared on continued mixing. Next 5 grams of a 5% Pd on carbon catalyst was added to the solution. The reaction mixture was placed in a hydrogenation flask and 35 psi of Hydrogen was added while the flask was shaken for 24 hours. The mixture was filtered to remove the 5% Pd/C, and then neutralized with NaHCO₃ filtered again, and placed on a rotary evaporator to remove the ethanol isolating approximately 44 grams of thick oily product.

Example 15

Reactive coating standard was made by mixing A-side of a CARC coating with the B-side of the CARC coating material stirring well, and then the water used for viscosity reduction was added and stirred. The coating was applied to the epoxy primed metal surface and allowed to dry for 2 days at ambient temperature. A water reducible two part urethane CARC coating meeting MIL-DTL-64159 was used (Hentzen A-07770GWU 383 green & B- 07775CMU). Approximately 120 coupons of 5 cm x 5 cm were made using an air spray paint gun.

Reactive Coating V1 was made by addition of Example 13 product at 1.5% (based on weight of A+B) into the A-side of a CARC coating, followed by good stirring for 15 minutes. The B-side of the CARC coating material was added and stirred, and then the water used for viscosity reduction was added and stirred. The coating was applied to the primed metal surface, allowed to dry for 2 days at ambient temperature, and then the samples were sanded to remove several mils of thickness to mimic severe wear in the field. Reactive Coating W1 was made by addition of Example 11 product at 1.5%

(based on weight of A+B) into the A-side of a CARC coating, followed by good stirring for 15 minutes. The B-side of the CARC coating material was added and stirred, and then the water used for viscosity reduction was added and stirred. The coating was applied to the primed metal surface, allowed to dry for several days at ambient temperature, and then the samples were sanded to remove several mils of thickness to mimic severe wear in the field.

Studies were performed with the V1 and W1 reactive coatings to determine their effectiveness in neutralizing both Chemical and Biological Warfare Agents. All initial work was conducted with agent simulants; for the G-agents the simulant was dimethyl methylphosphonate (CAS 756-79-6), for VX, the simulant was O,S-diethyl ethylthiophosphonate, for mustard the simulant was^-chloroethyl ethyl sulfide (CAS 693-07-2). The three biological simulants utilized were: Bacillus thuringiensis var. kurstaki (Btk, or Bt) a spore forming bacteria, Escherichia coli (Migula ATCC 15597) a vegetative bacteria, and bacteriophage MS2 (ATCC 15597-B2) as a simulant for virus.

The general protocol for CARC coated surface testing (done at about 21⁰C) involves: 1) Inoculate test coupon with a known quantity of chemical or biological agent stimulant; 2),Wait*60 minutes; 3) Wash the surface of the coupon with solvent. For chemical agents 4) Plate the coupon wash solution to determine the amount of amount of biological agent that remains viable. The percent of agent neutralized by the coating was as follows:

Various embodiments of the subject matter are described above in the Detailed Description. While these descriptions directly describe the above embodiments, it is understood that those skilled in the art may conceive modifications and/or variations to the specific embodiments shown and described herein. Any such modifications or variations that fall within the purview of this description are intended to be included therein as well. Unless specifically noted, it is the intention of the inventor that the words and phrases in the specification and claims be given the ordinary and accustomed meanings to those of ordinary skill in the applicable art(s). The foregoing description of various embodiments of the subject matter known to the applicant at this time of filing the application has been presented and is intended for the purposes of illustration and description. The present description is not intended to be exhaustive nor limit the subject matter to the precise form disclosed and many modifications and variations are possible in the light of the above teachings. The embodiments described serve to explain the principles of the subject matter and its practical application and to enable others skilled in the art to utilize the subject matter in various embodiments and with various modifications as are suited to the particular use contemplated. Therefore, it is intended that the subject matter not be limited to the particular embodiments disclosed for carrying out the subject matter.

While particular embodiments of the present subject matter have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from this subject matter and its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this subject matter. Furthermore, it is to be understood that the subject matter is solely defined by the appended claims. It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as "open" terms (e.g., the term "including" should be interpreted as "including but not limited to," the term "having" should be interpreted as "having at least," the term "includes" should be interpreted as "includes but is not limited to," etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particular claim containing such introduced claim recitation to subject matter containing only one such recitation, even when the same claim includes the introductory phrases "one or more" or "at least one" and indefinite articles such as "a" or "an" (e.g., "a" and/or "an" should typically be interpreted to mean "at least one" or "one or more"); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of "two recitations," without other modifiers, typically means at least two recitations, or two or more recitations).

Claims

WHAT IS CLAIMED IS:

1. A compound having the structure of Formula (I):

Wherein

R is selected from a group consisting of a hydrogen atom, methyl, ethyl, hydroxymethyl, sulfhydrylmethyl, methylsulfonic, sulfhydrylethyl, hydroxyethyl. isopropyl, isobutyl, sec-butyl, aminobutyl, hydroxyaminobutyl, aminopropyl, benzyl, ethylthiomethyl, carboxyethyl, carbamidoethyl, carboxymethyl, carbamidomethyl, 4-hydroxybenzyl, 3-indoylmethyl, 4- indoylmethyl, quanidinopropyl, aminomethyl, aminoethylaminomethyl, bis(aminoethyl)aminomethyl, aminoethyl, diethylamine, methylpiperazine, and polyetheφolyamines; and

Z is selected from a groups consisting of a hydrogen atom, methyl, ethyl, carboxylic acid, esters, and salts.

The compound of Claim 1 wherein the compound is reacted with a thermoplastic

The compound of Claim 2 wherein the thermoplastic is selected from a group consisting of polyethylene, polyethylene grafted maleic anhydride, poly(ethylene-co-methacrylic acid), poly(ethylene-co-zinc methacrylate)(Surlyn), polypropylene, polypropylene maleic anhydride copolymers, polyvinylchloride, polyvinyldichloride, polymethylmethacrylate, polyamides, polystyrene, poly(styrene-co-maleic anhydride), polyethyleneterephthalate, polybutyleneterephthalate, and blends and mixtures thereof.

4. The compound of Claim 1 wherein the compound is reacted with a thermoset resin.

5. The compound of Claim 4 wherein the thermoset resin is selected from a group consisting of unsaturated polyester resins, vinyl ester resins, epoxies, (poly)urethanes, phenolics, silanes, alkyds and blends and mixtures thereof

6. A compound having the structure of Formula (II):

("I) Wherein

R is selected from a group consisting of a hydrogen atom, methyl, ethyl, hydroxymethyl, sulfhydrylmethyl, methylsulfonic, sulfhydrylethyl, hydroxyethyl, isopropyl, isobutyl, sec-butyl, aminobutyl, hydroxyaminobutyl, aminopropyl, benzyl, ethylthiomethyl, carboxyethyl, carbamidoethyl, carboxymethyl, carbamidomethyl, 4-hydroxybenzyl, 3-indoylmethyl, 4- indoylmethyl, quanidinopropyl, aminomethyl, aminoethylaminomethyl, bis(aminoethyl)aminomethyl, aminoethyl, diethylamine, methylpiperazine, and polyetherpolyamines, and

7. The compound of Claim 6 wherein the compound is reacted with a thermoplastic

8. The compound of Claim 7 wherein the thermoplastic is selected from a group consisting of polyethylene, polyethylene grafted maleic anhydride, poly(ethylene-co-methacrylic acid), poly(ethylene-co-zinc methacrylate)(Surlyn), polypropylene, polypropylene maleic anhydride copolymers, polyvinylchloride, polyvinyldichloride, polymethylmethacrylate, polyamides, polystyrene, poly(styrene-co-maleic anhydride), polyethyleneterephthalate, polybutyleneterephthalate, and blends and mixtures thereof.

9. The compound of Claim 6 wherein the compound is reacted with a theπmoset resin.

10. The compound of Claim 9 wherein the thermoset resin is selected from a group consisting of unsaturated polyester resins, vinyl ester resins, epoxies, (poly)urethanes, phenolics, silanes, alkyds and blends and mixtures thereof.

11. A compound having the structure of Formula (III):

(III)

Wherein

R is selected from a group consisting of a hydrogen atom, methyl, ethyl, hydroxymethyl, sulfhydrylmethyl, methylsulfonic, sulfhydrylethyl, hydroxyethyl, isopropyl, isobutyl, sec-butyl, aminobutyl, hydroxyaminobutyl, aminopropyl, benzyl, ethylthiomethyl, carboxyethyl, carbamidoethyl, carboxymethyl, carbamidomethyl, 4-hydroxybenzyl, 3-indoylmethyl, 4- indoylmethyl, quanidinopropyl, aminomethyl, aminoethylaminomethyl, bis(aminoethyl)aminomethyl, aminoethyl, diethylamine, methylpiperazine, and polyetherpolyamines; and Z is selected from a groups consisting of a hydrogen atom, methyl, ethyl, carboxylic acid, esters, and salts.

12. The compound of Claim 11 wherein the compound is reacted with a thermoplastic.

13. The compound of Claim 12 wherein the thermoplastic is selected from a group consisting of polyethylene, polyethylene grafted maleic anhydride, poly(ethylene-co-methacrylic acid), poly(ethylene-co-zinc methacrylate)(Surlyn), polypropylene, polypropylene maleic anhydride copolymers, polyvinylchloride, polyvinyldichloride, polymethylmethacrylate, polyamides, polystyrene, poly(styrene-co-maleic anhydride), polyethyleneterephthalate, polybutyleneterephthalate. and blends and mixtures thereof.

14. The compound of Claim 11 wherein the compound is reacted with a thermoset resin.

15. The compound of Claim 14 wherein the thermoset resin is selected from a group consisting of unsaturated polyester resins, vinyl ester resins, epoxies, (poly)urethanes, phenolics, silanes, alkyds and blends and mixtures thereof.

16. A compound having the structure.of Formula (IV):

(IV) Wherein

R is selected from a group consisting of a hydrogen atom, methyl, ethyl, hydroxymethyl, sulfhydrylmethyl, methylsulfόnic, sulfhydrylethyl, hydroxyethyl, isopropyl, isobutyl, sec-butyl, aminobutyl, hydroxyaminobutyl, aminopropyl, benzyl, ethylthiomethyl, carboxyethyl, carbamidoethyl, carboxymethyl, carbamidomethyl, 4-hydroxybenzyl, 3-indoylmethyl, A- indoylmethyl, quanidinopropyl, aminomethyl, aminoethylaminomethyl, bis(aminoethyl)aminomethyl, amiπoethyl, diethylamine, methylpiperazine, and polyetherpolyamines; and Z is selected from a groups consisting of a hydrogen atom, methyl, ethyl, carboxylic acid, esters, and salts.

17. The compound of Claim 16 wherein the compound is reacted with a thermoplastic.

18. The compound of Claim 17 wherein the thermoplastic is selected from a group consisting of polyethylene, polyethylene grafted maleic anhydride, poly(ethylene-co-methacrylic acid), poly(ethylene-co-zinc methacrylate)(Surlyn), polypropylene, polypropylene maleic anhydride copolymers, polyvinylchloride, polyvinyldichloride, polymethylmethacrylate, polyamides, polystyrene, poly(styrene-co-maleic anhydride), polyethyleneterephthalate, polybutyleneterephthalate, and blends and mixtures thereof.

19. The compound of Claim 16 wherein the compound is reacted with a thermoset resin.

20. The compound of Claim 19 wherein the thermoset resin is selected from a group consisting of unsaturated polyester resins, vinyl ester resins, epoxies,

(poly)urethanes, phenolics, silanes, alkyds and blends and mixtures thereof.

21. A compound having the structure of Formula (V):

(V) Wherein

R is selected from a group consisting of a hydrogen atom, methyl, ethyl, hydroxymethyl, sulfhydrylmethyl, methylsulfonic, sulfhydrylethyl, hydroxyethyl, isopropyl, isobutyl, sec-butyl, aminobutyl, hydroxyaminobutyl, aminopropyl, benzyl, ethylthiomethyl, carboxyethyl, carbamidoethyl, carboxymethyl, carbamidomethyl, 4-hydroxybenzyl, 3-indoylmethyl, 4- indoylmethyl, quanidinopropyl, aminomethyl, aminoethylaminomethyl, bis(aminoethyl)aminomethyl, aminoethyl, diethylamine, methylpiperazine, and polyetherpolyamines; and

22. The compound of Claim 21 wherein the compound is reacted with a thermoplastic.

23. The compound of Claim 22 wherein the thermoplastic is selected from a group consisting of polyethylene, polyethylene grafted maleic anhydride, poly(ethylene-co-methacrylic acid), poly(ethylene-co-zinc methacrylate)(Surlyn), polypropylene, polypropylene maleic anhydride copolymers, polyvinylchloride, polyvinyldichloride, polymethylmethacrylate, polyamides, polystyrene, poly(styrene-co-maleic anhydride), polyethyleneterephthalate, polybutyleneterephthalate, and blends and mixtures thereof.

24. The compound of Claim 21 wherein the compound is reacted with a thermoset resin.

25. The compound of Claim 24 wherein the thermoset resin is selected from a group consisting of unsaturated polyester resins, vinyl ester resins, epoxies,

(poly)urethanes, phenolics, silanes, alkyds and blends and mixtures thereof.