Binding of tolmetin and salicylic acid to human serum albumin as a function of temperature

Abstract

When drug-protein binding data are evaluated thermodynamically standard free energy (delta G0), standard enthalpy (delta H0) and standard entropy (delta S0) are usually estimated from association constants (Ka) derived from binding data obtained at only two temperatures. Estimation of delta H0 involves the assumption of its constancy in the temperature range studied and linearity of a van't Hoff plot of ln Ka versus 1/T. Sometimes the assumption of such linearity is invalid for theoretical reasons and data obtained at only two temperatures contain no information concerning linearity of this plot. We present data for the binding of both tolmetin and salicylic acid to human serum albumin as a function of temperature which make doubtful the validity of using association constants of these drugs to derive thermodynamic constants other than delta G0 values.

Comparison of various capillary electrophoretic approaches for the study of drug–protein interaction with emphasis on minimal consumption of protein sample and possibility of automation†

“…Negative ∆H 0 and ∆S 0 values indicate that hydrogen bonding along with van der Waals forces play major roles in the binding between SA and BSA. Spontaneous reaction (the negative ∆G 0 value) is confirmed in the literature, on the other hand, different ∆H 0 and ∆S 0 values were referred to in the literature . Our data, with both negative ∆H 0 and ∆S 0 values, correspond with the data reported by Matias et al .…”

“…Our data, with both negative ∆H 0 and ∆S 0 values, correspond with the data reported by Matias et al . The heterogeneity in the data obtained from the literature (and their interpretation) can be explained by the relationship between the logarithm of the K b and the reciprocal of the temperature not being linear, as was pointed out by Behm et al., who even expressed doubt about the possibility of obtaining thermodynamic parameters other than ∆G 0 from K b . As it can be seen from the Table , the n i values are affected by temperature as well.…”

“…The interaction between BSA and SA was described by calculating the thermodynamic parameters according to the van't Hoff equation : where R is the gas constant, T is the absolute temperature, and K b is the binding constant at the corresponding T . The following data were obtained by the CE–FA method: the plot of ln K b versus 1/ T is shown in Fig.…”

“…(1) ⌬H 0 > 0 and ⌬S 0 > 0 → hydrophobic forces (2) ⌬H 0 < 0 and ⌬S 0 < 0 → van der Waals interactions and hydrogen bonds (3) ⌬H 0 < 0 and ⌬S 0 > 0 → electrostatic interactions The interaction between BSA and SA was described by calculating the thermodynamic parameters according to the van't Hoff equation [35,36]:…”