Synthesis and evaluation of novel phosphonated and bisphosphonated methacrylates with possible environmental and biomedical applications

Abstract

In this study, a series of mostly alkyl α-hydroxymethacrylate (RHMA)-derived novel monomers in four groups, and polymers of some of them were synthesized for various purposes including dental, bone-targeting and metal-binding applications. The first-group monomers, containing bisphosphonate, were synthesized from reaction of RHMA-derived ethyl or tert-butyl α-bromomethacrylate (EBBr, TBBr) with tetraethyl 4-hydroxybutane-1,1-diyldiphosphonate (A1, A2). Their homo- and copolymerizations with poly(ethylene glycol) methyl ether methacrylate, hydrolysis of bisphosphonate groups of one of the polymers to give a polymer with binding ability to hydroxyapatite (HAP) indicated their potential to deliver an attached drug to bone tissues. The monomers of the second group contain either bisphosphonic (B3), or carboxylic acid (B4), or the last two together (B5). They were synthesized by the reactions of tetraethyl 1-hydroxyethane-1,1-diyldiphosphonate with EBBr and TBBr (B1, B2) followed by hydrolysis of their bisphosphonate and/or tert-butyl groups. Hydrolytic stability, copolymerizations with commercial dental monomers and HAP interactions make these monomers promising candidates for dental adhesives. Aminophosphonate-containing methacrylates making up the third group were synthesized by reactions of diethyl aminomethylphosphonate or diethyl 2-aminoethylphosphonate with EBBr (C1, C2) or TBBr (C3, C4); or with 3-(acryloyloxy)-2-hydroxypropyl methacrylate (AHM) (C5, C6). C1-C4 gave crosslinked or soluble polymers depending on monomer structure and polymerization conditions. The fourth group contains eight water-soluble, zwitterionic monomers (D1-D8), synthesized by hydrolysis of the phosphonate or tert-butyl or both groups of C1-C4. The copolymerizations with diallyldimethylammonium chloride gave cyclic polymers which showed polyelectrolyte behaviour in water. Polymers obtained from these monomers may have potential applications in water treatment, coatings, and pharmaceutics.