Multipole electrostatic potential derived atomic charges in NDDO-methods with spd-basis sets

摘要

The recently introduced multipole approach for computing the molecular electrostatic potential (MEP) within the semiempirical neglect of diatomic differential overlap (NDDO) framework [Horn AHC, Lin Jr-H., Clark T (2005) Theor Chem Acc 114:159-168] has been used to obtain atomic charges of nearly ab initio quality by scaling the semiempirical MEP. The parameterization set comprised a total of 797 compounds and included not only the newly parameterized AM1* elements Al, Si, P, S, Cl, Ti, Zr, and Mo but also the standard AM1 elements H, C, N, O and F. For comparison, the ZDO-approximated MEP was also calculated analytically in the spd-basis. For the AM1*-optimized structures, single-point calculations at the B3LYP, HF and MP2 levels with the 6-31G(d) and LanL2DZP basis sets were performed to obtain the MEP. The regression analysis of all 12 combinations of semiempirical and ab initio MEP data yielded correlation coefficients of at least 0.99 in all cases. Scaling the analytical and multipole-derived semiempirical MEP by the regression coefficients yielded mean unsigned errors below 2.6 and 1.9 kcal mol(-1), respectively. Subsequently, for 22 drug molecules from the World Drug Index, atomic charges were computed according to the RESP procedure using XX/6-31G(d) (XX=B3LYP, HF, MP2) and scaled AM1* multipole MEP; the correlation coefficients obtained are 0.83, 0.85 and 0.83, respectively. Figure: Schematic representation of the atomic charge generation: The molecular electrostatic potential (MEP) is calculated using the AM1* Hamiltonian; then the semiempirical MEP is scaled to DFT or ab initio level, and atomic charges are generated subsequently by the restraint electrostatic potential (RESP) fit method.