RAPID COMMUNICATION Phosphonic Acid-Based Amphiphilic Diblock Copolymers Derived from ROMP

Forming nanostructures with controlled size and shape is one of the most challenging tasks in material science. Amphiphilic block copolymers are of special interest because of their ability to self-assemble on the nanoscale. The formation of micelles has potential applications such as in drug delivery, biosensors, and gene therapy. Ring-opening metathesis polymerization (ROMP) is a versatile technique for the preparation of well-defined block copolymers with narrow distribution of molecular weights. Several amphiphilic block copolymers obtained by the ROMP pathway have been investigated in the literature and were shown to form micelles and nanoparticles, and used as drug delivery materials. Phosphorus-containing polymers have broad application areas; besides their flameretardant properties, they are also used in biomaterials for their adhesive properties to metals, bone, and dentin. The incorporation of phosphonic acid into acrylic monomers used in the dental industry can promote both biocompatibility and adhesion to the teeth, because of the formation of calcium phosphonates and phosphonate complexes. Phosphonates, corresponding anions of phosphonic acid, have strong interactions with and adsorb very powerfully onto mineral surfaces. Phosphonic acid-based polymers have also found several applications such as chelating agents for heavy metal salts, ion-exchange resins, and fuel cell membranes. In this study, we present an approach for the synthesis of phosphonic acid type block copolymers derived from ROMP using ‘‘Grubbs’ third generation catalyst’’ [(H2-Imes)(3-Br-py)2-(Cl)2Ru 1⁄4 CHPh]. Block copolymer components, monomers 2 and 3, were synthesized by a nucleophilic exchange reaction and Mitsunobu coupling, respectively, using easily accessible starting material exo-oxabicyclo-[2.2.1]hept-5-ene-2,3-dicarboximide, 1 (Scheme 1). Then, 2 and 3 were polymerized sequentially to form block copolymers, 4a–c, with a high control of polymerization (Scheme 2). By cleavage of the phosphonate groups via transesterification with trimethylsilylbromide (TMSiBr) followed by the hydrolysis of the silylester group, the polymers were transformed into amphiphilic block copolymers, 5a–c (Scheme 2). The hydrodynamic radii of the formed micelles were investigated by dynamic light scattering (DLS). The diameter of the micelles can be varied through changes in the composition of the block copolymers while the overall polymer length is kept constant. Three series of block copolymers were synthesized by keeping the molecular weight constant (Mn,th 1⁄4 20,000 g/mol) with varying compositions (4:1; 1:1; 1:4, by weight ratio for monomers 2 and 3). For all of the series, the overall monomer/catalyst ratio was kept constant (60:1).