Comparison of different atomic charge schemes for predicting pKa variations in substituted anilines and phenols

A number of different methods have been proposed for assigning partial charges to the atoms of a molecule, including both quantum chemical and empirical schemes. A reasonable expectation for any successful calculational scheme is that the atomic charges it produces should vary in a manner consistent with chemical intuition and, more specifically, that these variations should be correlated in a sensible way with experimental observations. Seven of the most popular atomic charge schemes (Bader's AIM charges QAIM, electrostatic potential charges QESP, GAPT charges QGAPT, Gasteiger π charges QGast ,L owdin chargesQLow, Mulliken charges QMul, and charges derived from natural population analysis QNPA) were tested for their ability to represent variations in the pKa's of 19 monosubstituted anilines and 19 monosubstituted phenols. In most cases the calculations were performed at the B3LYP/6-311G ∗∗ level of theory. For the substituted anilines, the amino nitrogen, anilinium proton, and total amino group charges were taken as representative regression parameters, and for the phenols, the phenolic hydrogen, phenoxide oxygen, and hydroxyl group charges were employed. Overall, QAIM, QLow, and QNPA yielded the most successful correlations with the pKa's of these compounds, although for the phenol series, QGAPT and QMul also yielded good results. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem 90: 445-458, 2002

[1]  R. S. Mulliken.  Criteria for the Construction of Good Self‐Consistent‐Field Molecular Orbital Wave Functions, and the Significance of LCAO‐MO Population Analysis , 1962 .

[2]  P. Kollman,et al.  Encyclopedia of computational chemistry , 1998 .

[3]  George P. Ford,et al.  Atomic charges derived from a fast and accurate method for electrostatic potentials based on modified AM1 calculations , 1994, J. Comput. Chem..

[4]  Johann Gasteiger,et al.  Electronegativity equalization: application and parametrization , 1985 .

[5]  P. Löwdin.  Quantum Theory of Many-Particle Systems. I. Physical Interpretations by Means of Density Matrices, Natural Spin-Orbitals, and Convergence Problems in the Method of Configurational Interaction , 1955 .

[6]  Johann Gasteiger,et al.  Prediction of proton magnetic resonance shifts: The dependence on hydrogen charges obtained by iterative partial equalization of orbital electronegativity , 1981 .

[7]  Jerzy Cioslowski,et al.  A new population analysis based on atomic polar tensors , 1989 .

[8]  Peter C. Jurs,et al.  Estimation of pKa for organic oxyacids using calculated atomic charges , 1993, J. Comput. Chem..

[9]  Peter Politzer,et al.  On the problem of defining the charge on an atom in a molecule , 1968 .

[10]  Donald G. Truhlar,et al.  New Class IV Charge Model for Extracting Accurate Partial Charges from Wave Functions , 1998 .

[11]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[12]  Lee Griffiths,et al.  Approaches to charge calculations in molecular mechanics , 1982 .

[13]  Peter C. Jurs,et al.  Atomic charge calculations for quantitative structure—property relationships , 1992 .

[14]  Kenneth B. Wiberg,et al.  Comparison of atomic charges derived via different procedures , 1993, J. Comput. Chem..

[15]  C. Breneman,et al.  Determining atom‐centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis , 1990 .

[16]  Harold A. Scheraga,et al.  Determination of net atomic charges using a modified partial equalization of orbital electronegativity method. III. Application to halogenated and aromatic molecules , 1993, J. Comput. Chem..

[17]  F. Weinhold,et al.  Natural population analysis , 1985 .

[18]  M. Murcko,et al.  The Response of Electrons to Structural Changes , 1991, Science.

[19]  Harold A. Scheraga,et al.  Determination of net atomic charges using a modified partial equalization of orbital electronegativity method. 1. Application to neutral molecules as models for polypeptides , 1990 .

[20]  Per-Olov Löwdin,et al.  On the Nonorthogonality Problem , 1970 .

[21]  R. Bader.  Atoms in molecules : a quantum theory , 1990 .

[22]  J. Gasteiger,et al.  ITERATIVE PARTIAL EQUALIZATION OF ORBITAL ELECTRONEGATIVITY – A RAPID ACCESS TO ATOMIC CHARGES , 1980 .

[23]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[24]  W. Goddard,et al.  Charge equilibration for molecular dynamics simulations , 1991 .

[25]  L. E. Chirlian,et al.  Atomic charges derived from electrostatic potentials: A detailed study , 1987 .

[26]  Mark S. Gordon,et al.  General atomic and molecular electronic structure system , 1993, J. Comput. Chem..

[27]  R. J. Abraham,et al.  Charge calculations in molecular mechanics IV: A general method for conjugated systems , 1988 .

[28]  P. Seybold,et al.  Substituent effects on the physical properties and pKa of phenol , 2001 .

[29]  J. Murray,et al.  Comparison of quantum chemical parameters and Hammett constants in correlating pK(a) values of substituted anilines. , 2001, The Journal of organic chemistry.

[30]  P. Kollman,et al.  Atomic charges derived from semiempirical methods , 1990 .

[31]  P. Seybold,et al.  Substituent effects on the physical properties and pKa of aniline , 2000 .

[32]  R. S. Mulliken.  Electronic Population Analysis on LCAO–MO Molecular Wave Functions. I , 1955 .

[33]  A. Becke,et al.  Density-functional exchange-energy approximation with correct asymptotic behavior. , 1988, Physical review. A, General physics.