Schiff base complex conjugates of bovine serum albumin as artificial metalloenzymes for eco-friendly enantioselective sulfoxidation

Abstract

Artificial metalloenzymes (BSA-ML) have been prepared by non-covalent insertion of transition metal Schiff-base complexes, ML (L = 2-hydroxynaphthalen-1-naphthaldehyde and 3,4-diaminobenzenesulfonic acid; M = Co, Mn, V, Fe, Cr), into bovine serum albumin (BSA) as the host protein and were characterized by UV-visible spectroscopy, ESI-TOF mass spectrometry and molecular docking studies. The catalytic activities of the BSA-ML in the selective oxidation of various prochiral sulfides in aqueous media, using H₂O₂ as oxidant, have been evaluated. During the optimization process, pH and the concentrations of catalyst and oxidant were found to have a remarkable influence on both yield and enantioselectivity. In certain cases, BSA-ML gave satisfactory results in the oxidation of organic sulfides to sulfoxides (up to 100% conversion, 100% chemoselectivity, 96% ee and 500 h^-1 turnover frequency).

Fig. 1. (a) UV-visible spectra of 20 ìM BSA (yellow solid line), 20 ìM CrL complex (blue solid line) and 20 ìM BSA-CrL hybrid (red dashed line) in 0.05 M PBS buffer pH 7.45; (b) ESI-TOF MS spectrum of BSA and BSA-CrL.

Fig. 2. (a) Is the lowest energy binding mode of CrL to BSA; (b) is the close-up view of binding site of CrL on BSA corresponding to (a), and the selected amino acid residues are shown by stick model.

Fig. 3. (a) Chemoselectivity, (b) yield and (c) ee values under different pH values on the oxidation of thioanisole in PB at room temperature for 20 h. The mol ratios of H₂O₂ : thioanisole : BSA-ML (2.7 μmol) were 150 : 100 : 1. The sulfoxide of thioanisole was in the R configuration.

Scheme 1. Enantioselectivity of various prochiral sulfides oxidation using BSA-ML as the catalyst.

Fig. 4. (a) Comparison of averaging ee values (dark yellow), averaging yields (dark cyan) and turnover frequencies (purple) in the sulfoxidation reactions catalyzed by BSA-ML; (b) comparison of averaging ee values (dark yellow), averaging yields (dark cyan) in the sulfoxidation for different substrates. Reactions were performed in the optimal reaction conditions for different BSA-ML system.