A QSPR-Approach to the Estimation of the p K HB of Six-Membered Nitrogen-Heterocycles using Quantum Mechanically Derived Descriptors

Abstract

Descriptors derived from semiempirical (AM1) molecular orbital calculations have been used to construct a quantitative structure-property relationship (QSPR) for the thermodynamic hydrogen-bond basicity, p K(HB), of a series of six-membered aromatic nitrogen-heterocycles. The resulting model uses four-descriptors (the Coulson charge on the nitrogen atom, the energy of the localized nitrogen lone-pair orbital, the p-orbital contribution to this MO and an accessibility angle). The model gives r2(cv)=0.95 for 51 compounds with a standard deviation between calculation and experiment of 0.13 log units.

A Theoretical Evaluation of the pKHBand Δ$H{{{\,\ominus}\hfill \atop {\rm HB}\hfill}}}$ Hydrogen‐Bond Scales of Nitrogen Bases

“…Semiempirical AM1 calculations were proposed to evaluate the pK HB data of series of substituted pyridines and nitriles. Hennemann et al [17] defined no fewer than four descriptors of the base to unravel the different structural effects in the pyridine series. However, using the AM1-calculated enthalpies of hydrogen-bond formation between pFP and 22 substituted nitriles, Le Questel et al [18] found an encouraging correlation with a standard error of 0.17 pK units.…”

Economical and Accurate Protocol for Calculating Hydrogen-Bond-Acceptor Strengths

“…Other methods are based on experimentally measured properties such as the difference between octanol–water and cyclohexane–water partition coefficients or solvatochromic parameters (derived from spectroscopic data). − However, for these methods, experimental data must be available to derive the H-bond properties. On the other hand, various approaches on the basis of theoretically calculated properties such as the energies of lowest-unoccupied and highest-occupied molecular orbitals (LUMO and HOMO, respectively) and atomic charges, , self-atom polarizability and superdelocalizability, , the molecular electrostatic potential (MEP), , or combinations of these properties have been proposed. However, some of these approaches treat the H-bond as an isolated interaction and do not take the influence of the molecular environment into account.…”

A QSPR Study for the Prediction of the pKa of N-Base Ligands and Formation Constant Kc of Bis(2,2′-bipyridine)Platinum(II)-N-Base Adducts Using Quantum Mechanically Derived Descriptors

“…Numerous computational studies have attempted to predict pKa of organic compounds by applying different theoretical models [2][3][4][5][6][7][8][9][10][11][12][13]. Three main approaches have been employed in these theoretical models.…”