A calorimetric study of the influence of temperature on the self-association of amphiphilic antidepressant drugs in aqueous solution

Relative apparent molar enthalpies have been determined as a function of co ncentration (0.0001 to 0.2 mol kg(-1)) by heat conduction calorimetry for a queous solutions of the structurally related antidepressant drugs imipramin e and domipramine in water over the temperature range 288 to 308 K. Critica l concentrations determined from inflections in these plots for both drugs had minimum values at 298 K. The concentration dependence of the relative a pparent molar enthalpy could be quantitatively described using a mass actio n model of association based on the Guggenheim equations for the activity c oefficients of mixed electrolytes, Derived values of the monomer-counterion interaction coefficient for imipramine became increasingly negative with a n increase in temperature over the temperature range 293 to 303 K, indicati ve of an increasing degree of premicellar association. In contrast, negativ e monomer-counterion interaction coefficients were obtained far domipramine at only 303 and 308 K, suggesting an absence of premicellar association at lower temperatures. Values derived for the molar enthalpy of micellization of both drugs from the mass action model indicate an increasingly exotherm ic process with increase in temperature; positive values at 288 and 293 ii arise from hydrophobic interactions while the negative values at higher tem peratures suggest the importance of London dispersion interactions as the m ajor driving force for aggregation. (C) 2000 Academic Press.