124: Immobilized CuPc–BSA artificial metalloenzyme beads for highly enantioselective oxidations in aqueous medium

Abstract: We report a immobilized artificial metalloenzyme, CuPc–BSA@silica, formed by hosting copper(II) phthalocyanine (CuPc) within bovine serum albumin (BSA) and immobilizing the biohybrid in crosslinked silica beads. In aqueous medium, this heterogeneous catalyst promotes enantioselective oxidations across sulfoxidation, epoxidation, and benzylic C–H oxidation, achieving up to 97% conversion and up to 100% ee across diverse substrates. Mechanistic studies support a radical pathway: EPR spin-trapping with DMPO indicates formation of short-lived oxygen-centered radicals under turnover conditions, while TEMPO quenching experiments are consistent with radical intermediates contributing to substrate oxidation. We propose that CuPc activates the oxidant to generate reactive radical equivalents within a protein-defined microenvironment that pre-organizes substrates and imposes stereocontrol. This immobilized platform couples enzyme-like selectivity with practical recovery and reuse and is being expanded toward preparation of >6 API-relevant chiral products using a unified aqueous-medium oxidation workflow.