The invention relates to enzyme-mediated polymerization methods and products, particularly regarding polymerization of substituted ethylene monomers, even more particularly in the presence of a peroxide source.
Polymerization processes have made possible many advances in materials science, especially plastics, that have transformed the world in a matter of decades. Most polymerization processes can be categorized into four distinct groups, based on the mechanism of the polymerization reaction. One of the most widely utilized of these processes is free-radical polymerization, wherein, typically, an initiator, such as benzoyl peroxide, is thermally dissociated to provide a radical source that begins the polymerization process, wherein the reactive terminus of the growing polymer chain is characterized by having an unpaired electron. Anionic and cationic processes may be initiated by nucleophiles and Lewis acids, respectively, and the reactive terminus of the growing polymer chain is characterized by being nucleophilic in an anionic process, and by being electrophilic in a cationic process. The fourth category includes transition metal-mediated processes, such as Ziegler-Natta polymerizations, wherein the reactive terminus of the growing polymer chain is associated with a transition metal catalyst.
The monomer undergoing polymerization determines, in part, the mechanism of the polymerization. For example, polystyrene, commonly used for insulation, packing materials, and a variety of other applications, can be formed from styrene utilizing any of the above mechanisms. As of now, the free-radical process is most commonly used for large-scale industrial processes. Most of the processes except Zeigler-Natta polymerization produce atactic, amorphous polystyrene. Atactic describes a polymer comprising a series of stereogenic carbons wherein the stereochemistry of successive stereogenic carbons is irregular or random. Isotactic describes a polymer wherein successive stereogenic carbons tend to have the same stereochemical designation, e.g., RRRRR. Syndiotactic, on the other hand, describes a polymer wherein successive stereogenic carbons alternate in stereochemical designation, e.g., RSRSRSRS. Zeigler-Natta polymerizations can produce either isotactic or syndiotactic polystyrene, depending on the catalyst and reaction conditions.
Anionic polymerization of styrene, as described in U.S. Pat. No. 4,859,748 to Dow Chemical Company, may be initiated by n-butyllithium (NBL), and the molecular weight (MW) of the resulting polymer can be controlled by varying the ratio of monomer to initiator. Polymerization may be terminated by adding an electrophile, such as carbon dioxide, to react with the anionic terminus of the growing polymer chains. However, n-butyllithium is highly reactive and potentially dangerous, and requires the use of toxic organic solvents in the reaction medium.
The cationic polymerization of styrene has proved difficult because the fast termination rates make high molecular weight polymers difficult to obtain, as described in U.S. Pat. Nos. 4,087,599, 4,112,209, and 4,161,573 to Dow Chemical Company, and so this process has not been commonly employed in industry. A typical Lewis acid initiator is BF3, using water as a cocatalyst. Again, this protocol prevents the use of water as a solvent, and relies instead on toxic organic solvents.
As stated above, isotactic and syntiotactic polystyrene are available through Zeigler-Natta polymerization of styrene. N. Ishihara et al., Macromolecules, 19, 2464, 1986, and U.S. Pat. Nos. 5,064,918, 5,045,517, and 5,196,490 to Dow Chemical Company. The isotactic form may be produced by using an aluminum-activated TiCl3 catalyst, and syndiotactic form may be prepared using soluble titanium complexes, such as (xcex75xe2x80x94C5H5)TiCl3, in combination with a partially hydrolyzed alkylaluminum, such as methylalumoxane. The reaction may be performed in the absence of solvent, or in organic solvents such as benzene, toluene, pentane, hexane. The molecular weight of the resulting polymer may be varied by changing the catalyst, amount of catalyst, and amount of monomer charged. Because of the sensitivity of the catalyst systems, these procedures require that the starting materials be highly purified, and water may not be present in the reaction mixture. Also, the final product typically must be separated from the metal catalyst.
For example, free-radical polymerization of styrene, such as described in U.S. Pat. No. 5,145,924 to Dow Chemical Company, may be used to produce atactic, amorphous polystyrene in a wide range of molecular weights. Higher molecular weight polymers can conveniently prepared using anionic polymerization. However, due to the faster reaction rates and shorter reaction times required for an analogous free-radical process, polystyrene can be made more inexpensively using a free-radical process. The starting materials need not be purified and initiator residues need not be removed, adding to the convenience of free-radical techniques. The molecular weight of the product polymer may be controlled by using different initiators, changing the reaction temperature (generally 100-170xc2x0 C.), or adding chain transfer agents, such as ethylbenzene. The high reaction temperatures involved generally preclude the use of aqueous solvent, and so such procedures often use toxic organic solvents.
Polyacrylamide, another commercially useful polymer (see, for example, U.S. Pat. Nos. 5,868,087, 5,863,650, and 5,873,991), is typically produced by a highly exothermic free-radical process in aqueous medium. The quantity of heat generated is normally handled in one of two ways: the reaction temperature is permitted to rise to around 90xc2x0 C. in a standard cooled reaction vessel, or the reaction is conducted in thin films to provide a high surface area-to-volume ratio for heat dispersion, thereby limiting the temperature increase. Additional techniques for producing polyacrylamide are described in U.S. Pat. Nos. 4,138,839 and 4,132,844 to American Cyanamid Company. U.S. Pat. No. 4,439,332 to American Cyanamid further describes a technique for copolymerizing acrylamide with acrylic acid in an inverse emulsion process using sorbitan monooleate as a surfactant. This technique helps to avoid high solution viscosities.
Polymers of acrylate, methacrylate, and related esters, are typically manufactured using free-radical processes from the requisite monomers. Polymethylmethacrylate is also known as Lucite(copyright) and Plexiglas(copyright). Copolymers are often produced for their superior properties. The resulting polymers are atactic. Methacrylic polymers are often prepared in the absence of solvent, the method of choice for production of sheets, rods, tubes, molding and extrusion compounds, as described in U.S. Pat. Nos. 3,113,114 to DuPont, 3,382,209 to American Cyanamid, and 3,376,371 to Swedlow Inc. Both acrylic and methacrylic polymers may be prepared using an organic solvent, such as benzene, toluene, isopropyl alcohol, isobutyl alcohol, chloroform, orcarbon tetrachloride. The molecular weight can be controlled by using a chain transfer agent, changing the radical initiator, concentrations of the monomers or initiator, the solvent, or the temperature. Typical reaction times are several hours (for methacrylates) to 24 hours (for acrylates). Reaction temperatures are higher for methacrylates (e.g., 140xc2x0 C.) than for acrylate polymers (e.g., 80xc2x0 C.). Emulsion polymerization is an even more common method for polymerization of these monomers, accounting for 70% of acrylate monomer consumption. No solvents are required and the reaction is much more rapid than the analogous solution-phase process, typically proceeding to completion in several hours. Reaction temperatures are generally 75-90xc2x0 C. U.S. Pat. Nos. 3,458,466 to Dow Chemical Company and 3,344,100 to B.F. Goodrich.
Anionic polymerization is also possible for acrylate and methacrylate monomers, particularly for generating tactic methacrylic polymers of narrow PDI and controlled molecular architecture. Organometallic compounds such as n-butyllithium are used as initiators. Nonpolar solvents usually yield isotactic polymers while in polar solvents syndiotactic polymers usually result. The reaction conditions must be carefully controlled to obtain high degrees of stereoregularity. This method has not, however, found significant commercial utility, and again requires the use of toxic organic solvents.
A general method for producing polymers of substituted ethylenes such as styrene, acrylamide, and acrylate and methacrylate esters that does not require the use of high temperatures, toxic organic solvents, reactive reagents, or rigorous purification of starting materials or products would provide a convenient polymerization process. Such a process that generated stereoregular polymers would be a further advance.
The present invention pertains to the use of peroxidases such as horseradish peroxidase (HRP), soybean peroxidases, and a diversity of related enzymes in the catalysis of vinyl monomer polymerizations. The polymerizations may be performed at ambient temperature in the presence of low concentrations of hydrogen peroxide and a reducing substrate. Polymers formed by this method may have very high molecular weights. By this method, high molecular weight polymers can be formed rapidly and at room temperature. Furthermore, this procedure may be used to produce stereoregular polymers. The present method tolerates a range of reaction conditions, including emulsion and reverse emulsion conditions. Moreover, the present method may be applied to the preparation of a wide range of copolymers, such as MMA with acrylamide and MMA with sodium acrylate. In certain embodiments, the present method may be used to prepare cross-linked polymers.
Thus, in one embodiment, the invention provides a method for polymerizing substituted ethylene monomers by combining at least one substituted ethylene monomer, a peroxide source, an enzyme, a transfer agent, and an organic solvent. The peroxide source may be hydrogen peroxide. The enzyme may be horseradish peroxidase, soybean peroxidase, or lignin peroxidase. The substituted ethylene monomer may be a methacrylate ester, acrylate ester, acrylamide, styrene, acrylic acid, or a salt thereof. The organic solvent may be tetrahydrofuran (THF), dimethyl formamide (DMF), acetone, or dioxane. The method may be performed using an emulsion or an inverse emulsion. The transfer agent may comprise a xcex2-dicarbonyl. The enzyme may be a recombinant enzyme, a thermophilic enzyme, a mesophilic enzyme, or an enzyme active below 0xc2x0 C.
In another embodiment, the invention provides a method for polymerizing substituted ethylene monomers by combining at least one substituted ethylene monomer, a peroxide source, an enzyme such as soybean peroxidase, chloroperoxidase, xanthine oxidase, or alcohol oxidase, and a transfer agent. The various reagents, solvents, and conditions may be selected as outlined above.
In yet another embodiment, the invention provides a method for polymerizing substituted ethylene monomers by combining under an inert atmosphere at least one substituted ethylene monomer, a peroxide source, an enzyme, and a transfer agent. The various reagents, solvents, and conditions may be selected as outlined above.
In still another embodiment, the invention provides a method for copolymerizing substituted ethylene monomers by combining at least two substituted ethylene monomers, a peroxide source, an enzyme, and a transfer agent. The various reagents, solvents, and conditions may be selected as outlined above.
In a further embodiment, the invention provides a method for polymerizing substituted ethylene monomers, comprising combining at least one substituted ethylene monomer, a peroxide source, an enzyme, and a transfer agent to produce a polymer at least 85% isotactic or at least 85% syndiotactic. The various reagents, solvents, and conditions may be selected as outlined above.
In another embodiment, the invention also provides a method for polymerizing a compound of the general formula (I): 
wherein
M represents H, an alkali metal, an alkaline earth metal, or an ammonium counterion, and
R represents, independently for each occurrence, H, a halogen, a ketone, an aldehyde, an ester, an amide, a carboxyl, a sulfonyl, a sulfoxide, an acylamino, a lower alkyl group, a lower alkenyl group, a lower alkynyl group, or an aryl group, comprising combining
a compound of the general formula (I),
a peroxide source,
an enzyme capable of generating a radical in the presence of a peroxide, and
a transfer agent.
The various reagents, solvents, and conditions may be selected as outlined above.
In another aspect, the invention provides a poly(methacrylate ester) which is at least 85% syndiotactic, such as a polymer produced by one of the methods outlined above.
USPTO Backgrounds
USPTO Backgrounds