Mechanism of interaction between human serum albumin and N-alkyl phenothiazines studied using spectroscopic methods.

The binding characteristics of human serum albumin (HSA) with N-alkyl phenothiazines derivatives (NAP) viz., levomepromazine monomaleate (LMM) and propericiazine (PPC) have been studied by employing fluorescence, absorption, circular dichroism and FT-IR techniques. The Stern-Volmer quenching constant, K(SV) values were found to decrease with increase in temperature thereby indicating the presence of static quenching mechanism in the interactions of NAP with HSA. The number of binding sites, n and the binding constant, K were noticed to be, respectively, 1.11 and (5.188+/-0.034)x10(4) M(-1) for LMM and 1.06 and (4.436+/-0.066)x10(4) M(-1) for PPC at 298 K. The negative value of enthalpy change and positive value of entropy change in the present study indicated that the hydrophobic forces played a major role in the binding of NAP to HSA. The circular dichroism and FT-IR spectral data revealed the conformational changes in the structure of protein upon its interaction with NAP. The binding distances and the energy transfer efficiency between NAP and protein were determined based on Förster's theory of energy transfer. The decreased binding constants of HAS-LMM and HAS-PPC systems in presence of common ions indicated the availability of higher concentration of free drug in plasma.