Three-Dimensional Correlation AnalysisA Novel Approach to the Quantification of Substituent Effects
Artem R Cherkasov, Dennis G. Sprous, Ridong Chen · The Journal of Physical Chemistry A · 2003
A new method to quantify the substituent effect, called “3D correlation analysis” (3D-CAN), is presented. This approach employs an atomic level of consideration of substituent effects and is developed on the basis of empirical inductive and steric constants. However, unlike traditional correlation analysis, 3D-CAN takes into account the three-dimensional structure of substituents. Extensive datasets of experimental dissociation constants for a broad range of carboxylic acids and protonated amines (including a number of polypeptides) have been accurately reproduced in the framework of the developed novel technique. New formulas allowing calculation of p K a values for 826 carboxylic acids and 802 protonated amines have been established, and the possibility of interpretation of the physical nature of the substituent effects within the framework of 3D-CAN is presented in the present paper. This validates the methodology as a powerful technique broadly applicable to general reaction phenomena.