Bioinspired Flavin-Based Supramolecular Materials for Catalyzing Baeyer-Villiger Oxidation.

Abstract

The selective oxygenation of organic compounds via Baeyer-Villiger (B-V) oxidation is crucial for producing value-added chemicals. Although biomimetic catalysts inspired by Baeyer-Villiger monooxygenase (BVMO) and employing a flavin cofactor have shown promise, their effectiveness has been limited by the difficulty in replicating enzymatic active sites, particularly for producing versatile lactones with low ring strain (e.g., valerolactone derivatives). In this work, we design amphiphilic alkylated arginine surfactants that self-assemble into a guanidinium-terminated micellar scaffold, incorporating both arginine and a hydrophobic pocket to mimic the microenvironment of the BVMO active site. This scaffold positions flavin mononucleotide (FMN) and manganese porphyrin centers to enable electron transfer and cooperative catalysis, inspired in part by natural reductases, such as cytochrome P450. In the presence of O₂ as the sole oxidant, this system efficiently oxidizes NADH, transferring electrons first to FMN and then to manganese porphyrin to generate high-valent Mn-oxo intermediates. These intermediates selectivity oxidize various sulfides to corresponding sulfoxides (yield and selectivity as high as 85% and over 98%) and convert cyclopentanone derivatives into the corresponding lactones (yield and selectivity as high as 46% and 100%) of industrial relevance. This strategy integrates supramolecular design with enzyme mimicry, offering a sustainable and highly selective platform for industrial oxidation reactions.