Binding of a chromen-4-one Schiff’s base with bovine serum albumin: capping with β-cyclodextrin influences the binding

Abstract

This work deals with the synthesis of 6-methyl-3-[(4′-methylphenyl)imino]methyl-4H-chromen-4-one (MMPIMC), its binding to β-cyclodextrin, and the influence of the cyclodextrin complexation on the compound’s binding to bovine serum albumin (BSA). The 1:2 stoichiometry for the complexation of MMPIMC with β-cyclodextrin is determined with the binding constant of 1.90 × 10⁴ M⁻². The structure of host–guest complex plays a role in protein binding of MMPIMC. One- and two-dimensional NMR spectra are used to determine the mode of binding of the guest to β-cyclodextrin cavity and the structure of the inclusion complex is proposed. The binding of MMPIMC with BSA in the absence and the presence of β-cyclodextrin is studied. The binding strengths of MMPIMC–BSA (1.73 × 10⁵ M⁻¹) and β-cyclodextrin-complexed MMPIMC–BSA (9.0 × 10⁴ M⁻¹) show difference in magnitude. The Förster Resonance Energy Transfer efficiency and the proximity of the donor and acceptor molecules, are modulated by β-cyclodextrin. Molecular modeling is used to optimize the sites and mode of binding of MMPIMC with bovine serum albumin.

Keywords:

• chromen-4-one Schiff’s base
• bovine serum albumin
• β-cyclodextrin
• COSY
• ROESY
• FRET

Acknowledgments

This work is financially supported by the SERB–Department of Science and Technology (DST), Government of India (Project file: SR/FT/CS-062/2009). We express our sense of gratitude to the DST. SAIF, Indian Institute of Technology–Madras, Chennai, helped in NMR measurements. We thank the Dean-Research and the Chancellor of Karunya University.