TEMPERATURE-DEPENDENCE OF THE ACID DISSOCIATION OF ATENOLOL

The acid dissociation constant of atenolol, a beta-receptor blocking d rug, was determined by potentiometric titration in aqueous ethanol (10 % ethanol v/v) in the range 19.8 - 38.0 degrees C. A linear relation b etween pK(a) and temperature (degrees C) was found for this range of t emperature: pK(a) = -0.306.T + 10.241 (r = -0.9982). At 37.0 degrees C the pK(a) value calculated for atenolol is 9.11. Therefore, in the di fferent human body fluids, this drug is mostly in its protonated form. The calculated thermodynamic parameters associated with the acid-base equilibrium involving this secondary amine are: Delta G degrees = 12. 95 kcal.mol(-1), Delta H = 12.77 kcal.mol(-1), and Delta S degrees = - 0.60 cal.mol(-1).K-1, respectively.