Use of Electron Densities in Comparative Molecular Field Analysis (CoMFA): A Quantitative Structure Activity Relationship (QSAR) for Electronic Effects of Groups

The description of field‐induction σ (σi) parameters in a Comparative Molecular Field Analysis has been previously attempted by incorporating electrostatic fields computed either from point charges or from electrostatic potentials. Also, σ as well as σi have been correlated for a series of groups (–X) with the lowest electrostatic potential around the nitrogen in a series of singly substituted (NH2 – X) amines [6,7]. Here a correlation is established between both field‐induction and resonance σ (σi and σr respectively) parameters for a series of groups (–X) and electron densities of molecules (R‐X) substituted with these groups, incorporated into a Comparative Molecular Field Analysis (CoMFA). The correlation has been established for a series of singly substituted amines (R=NH2‐) as well as para substituted benzoic acids (R=HOOC(p) ‐ C6H4‐) with the correlation coefficients being explained quite well. The crossvalidated r2 (q2) as well as the predicted r2 for a different series of groups have provided valid stress tests for the correlations. The electron densities for the various substituted amines are calculated using the AMI Hamiltonian in MOPAC5 [19].