The adsorption of an anticancer hydrazone by protein: an unusual static quenching mechanism

Abstract

A novel hydrazone, 4-chloro-N′-(pyridin-2-ylmethylene)benzohydrazide (CPBH) has been synthesized through a one-pot synthesis method and used as a chemical probe to find the structural cause of the unusual static quenching mechanism in the interaction with serum albumin. The adsorption of CPBH by bovine/human serum albumin (BSA/HSA) has been investigated systematically by comprehensive spectroscopy, modeling, electrochemistry and microcalorimetry under physiological conditions. CPBH forms a complex with BSA/HSA with the binding site in Sudlow's site I of BSA/HSA. The adverse temperature dependence in the unusual static quenching is found to be a reasonable consequence of the large activation energy requirement in the binding process, which is required to overcome the structural block and it is a direct result of the unique microstructure of the binding pocket.