S. Randall Holmes-Farley

Adhesion promotion and corrosion prevention using thin anisotropic coatings

Using sol-gel technology, thin organic/ceramic (ceramer) coatings have been applied to metal surfaces to enhance such surface properties as adhesion promotion and corrosion prevention. Isotropic coatings have been found to be effective in certain applications such as corrosion prevention, but the formation of anisotropic (functionally gradient) coatings permits greater flexibility over the resulting properties. Isotropic coatings derived from tetraethoxysilane, for example, have been found to effectively inhibit corrosion while being only 100-1000 A thick. These coatings do not, however, promote adhesion. Thin coatings made from traditional silane adhesion promoters alone are unable to prevent corrosion of metallic substrates. Using monomers with appropriate reactivities permits the single-step synthesis of anisotropic coatings that can both promote adhesion and prevent corrosion. These types of anisotropic coatings allow the physical and chemical properties of a coating to be varied as a function of the ...

AMINE FUNCTIONALIZED POLYETHERS AS BILE ACID SEQUESTRANTS: SYNTHESIS AND BIOLOGICAL EVALUATION

A series of amine functionalized polymers based on polyether backbones was prepared by the chemical modification of poly(epichlorohydrin) and poly(2-chloroethylvinyl ether). Nucleophilic substitution of pendant chloroalkyl groups offers a versatile route to prepare hydrophilic, cationic polymers. Through the choice of appropriate experimental conditions, including solvent, temperature, and amine reagent, a high degree of substitution at the chloromethyl groups can be achieved. Depending on the nature of the amine used, both water-soluble and amphiphilic cationic polymers were obtained. Crosslinked hydrogels were prepared by either subsequent crosslinking of the amine functional polyethers or by reaction of chloroalkyl polyethers with multifunctional amines. These amine functional polyethers exhibited promising bile acid sequestration properties during in vivo experiments using hamsters as animal models, providing a novel approach for treating hypercholesterolemia. Some of these polymers show efficacy superior to commercially available bile acid sequestrants. The results suggest that these novel polyammonium gels may be useful as cholesterol lowering agents.

Three Generations of Bile Acid Sequestrants

Cholestyramine, the first bile acid sequestrant to be marketed, has been in use for over 20 years. Despite its low potency, requiring 16-24 g of polymer to achieve 20% LDL cholesterol reduction in hypercholesterolemic individuals, only one other sequestrant, colestipol, has come to market in the ensuing period. GelTex Pharmaceuticals has been involved for over six years in the discovery and development of new, more potent polymeric sequestrants. Two binding mechanisms are presented — one that operates via an aggregate binding structure and one that is effective via a defined site binding structure. These two binding mechanisms are compared and contrasted through bile acid binding isotherms. The best of these new sequestrants bind bile acids through a combination of hydrophobicity and ion exchange. Optimization and balancing of each of these interactions led us to more potent materials. The first of these, colesevelam hydrochloride is expected to be three to four times more potent than cholestyramine. A third generation product is still in research at GelTex. With another twofold increase in potency possible, single tablet therapy may become a reality.

The mechanism of cure initiation of a surface-activated adhesive

The mechanism of cure initiation of a recently developed surface-activated adhesive is described. This one-part acrylic adhesive is catalyzed to cure by interaction with a zinc substrate. The critical ingredients for surface initiation are a sulfonyl halide, a copper salt, and an acid. The first step is reduction of the sulfonyl halide to a zinc sulfinate salt on the metal surface. The sulfinate then becomes protonated through action of the acid and is released from the surface. The sulfinic acid interacts with copper ion, perhaps through an intermediate sulfinyl sulfone moiety, and subsequently initiates polymerization of the methacrylate monomers.