Theoretical calculations on the basicity of amines: Part 1. The use of molecular electrostatic potential for p Ka prediction

Abstract

Good linear correlations ( r = 0.903 − 0.974) were found between the p K a, of nitrogen bases (pyridine-, aniline-derivatives, aliphatic amines) measured in aqueous solution and the minimum of the molecular electrostatic potential. The prediction of p K a for different types of amines seems possible with an accuracy of ~ 0.5 units. Using bond-increment potential calculations the estimation can be applied even for biomolecules being related to drug design. Correct consideration of both the molecular conformations and formation of the hydrogen-bonds in aqueous solutions is a prerequisite in obtaining reliable p K a values.