Sanguinarine is an anticancer plant alkaloid that can exist in the charged iminium and neutral alkanolamine forms. The thermodynamics of the interaction of the two forms with human serum albumin was investigated using calorimetric techniques, and the data supplemented with circular dichroism and spectrofluorimetric studies. The thermodynamic results show that there is only one class of binding for sanguinarine on HSA. The equilibrium constant was four times higher for the alkanolamine (K-a = 2.18 . 10(5) M-1) than for iminium (K-a = 5.97 . 10(4) M-1). The binding was enthalpy driven for iminium and favoured by both a negative enthalpy and a stronger favourable entropy contribution for the alkanolamine. Temperature dependent calorimetric data yielded values of Delta C-p(degrees) that are consistent with the involvement of different molecular forces in the complexation of the two forms of sanguinarine to HSA. The fluorescence quenching data suggest a static quenching mechanism. Synchronous fluorescence and circular dichroic data are consistent with a conformational change in the protein on binding that was also higher for the alkanolamine form. (C) 2011 Elsevier Ltd. All rights reserved.