Rhenium(I) Block Copolymers Based on Polyvinylpyrrolidone: A Successful Strategy to Water-Solubility and Biocompatibility

A series of diphosphine Re(I) complexes Re1-Re4 have been designed via decoration of the archetypal core {Re(CO)(2)(N boolean AND N)} through the installations of the phosphines P-0 and P-1 bearing the terminal double bond, where N boolean AND N = 2,2 '-bipyridine (N boolean AND N1), 4,4 '-di-tert-butyl-2,2 '-bipyridine (N boolean AND N2) or 2,9-dimethyl-1,10-phenanthroline (N boolean AND N3) and P-0 = diphenylvinylphosphine, and P-1 = 4-(diphenylphosphino)styrene. These complexes were copolymerized with the corresponding N-vinylpyrrolidone-based Macro-RAFT agents of different polymer chain lengths to give water-soluble copolymers of low-molecular p(VP-l-Re) and high-molecular p(VP-h-Re) block-copolymers containing rhenium complexes. Compounds Re1-Re4, as well as the copolymers p(VP-l-Re) and p(VP-h-Re), demonstrate phosphorescence from a (MLCT)-M-3 excited state typical for this type of chromophores. The copolymers p(VP-l-Re#) and p(VP-h-Re#) display weak sensitivity to molecular oxygen in aqueous and buffered media, which becomes almost negligible in the model physiological media. In cell experiments with CHO-K1 cell line, p(VP-l-Re2) and p(VP-h-Re2) displayed significantly reduced toxicity compared to the initial Re2 complex and internalized into cells presumably by endocytic pathways, being eventually accumulated in endosomes. The sensitivity of the copolymers to oxygen examined in CHO-K1 cells via phosphorescence lifetime imaging microscopy (PLIM) proved to be inessential.

Automated summary

A series of diphosphine Re(I) complexes Re1-Re4 were designed by decorating the archetypal core {Re(CO)(2)(N boolean AND N)} with phosphines bearing a terminal double bond. These complexes were copolymerized with Macro-RAFT agents to form water-soluble copolymers containing rhenium complexes. The copolymers exhibited phosphorescence from a (MLCT)-M-3 excited state and low sensitivity to molecular oxygen in physiological media.