Modeling the H bond donor strength of OH, NH, and CH sites by local molecular parameters

Abstract

A quantum chemical model is introduced to predict the H-bond donor strength of monofunctional organic compounds from their ground-state electronic properties. The model covers -OH, -NH, and -CH as H-bond donor sites and was calibrated with experimental values for the Abraham H-bond donor strength parameter A using the ab initio and density functional theory levels HF/6-31G** and B3LYP/6-31G**. Starting with the Morokuma analysis of hydrogen bonding, the electrostatic (ES), polarizability (PL), and charge transfer (CT) components were quantified employing local molecular parameters. With hydrogen net atomic charges calculated from both natural population analysis and the ES potential scheme, the ES term turned out to provide only marginal contributions to the Abraham parameter A, except for weak hydrogen bonds associated with acidic -CH sites. Accordingly, A is governed by PL and CT contributions. The PL component was characterized through a new measure of the local molecular hardness at hydrogen, eta(H), which in turn was quantified through empirically defined site-specific effective donor and acceptor energies, EE(occ) and EE(vac). The latter parameter was also used to address the CT contribution to A. With an initial training set of 77 compounds, HF/6-31G** yielded a squared correlation coefficient, r(2), of 0.91. Essentially identical statistics were achieved for a separate test set of 429 compounds and for the recalibrated model when using all 506 compounds. B3LYP/6-31G** yielded slightly inferior statistics. The discussion includes subset statistics for compounds containing -OH, -NH, and active -CH sites and a nonlinear model extension with slightly improved statistics (r(2) = 0.92).

Interpretation of experimental hydrogen-bond enthalpies and entropies from COSMO polarisation charge densities

“…Kenny 12 used the electrostatic potential as a quantum chemical descriptor for HBA strength of nitrogen bases. Schwöbel and coworkers [13][14][15][16] presented several studies, in which they demonstrate the suitability of local frontier orbital descriptors 17 for the predictive quantification of Abraham's HBA and HBD parameters of a chemically much broader range of donor and acceptor sites.…”

In Silico Investigation of the Thyroid Hormone Activity of Hydroxylated Polybrominated Diphenyl Ethers

“…31 In this research, a series of local molecular parameters calculated by ab initio methodology is employed to develop a new quantum chemical model to represent the interactions between TRβ and HO-PBDEs. These descriptors were originally introduced by Klamt 32,33 and were successfully applied to the estimation of the hydrogen bonding strength, 34,35 a process observed between the hydroxyl groups of HO-PBDEs and the amino acid residues of TRβ, acting as a characteristic interaction for the thyroid hormone activity of HO-PBDE molecules. 20,30 In addition, these parameters have also been shown capable of addressing the electrostatic interactions, 34,35 another important molecular interaction that governs the activity of HO-PBDEs to TRβ.…”

A combined experimental and theoretical approach to the study of hydrogen bond interaction in the binary mixture of N-methylimidazole with water

“…The investigations of non-covalent interactions, particularly hydrogen bond, are one of the most frequently studied aspects not only for their diverse molecular topologies, but also for their potential applications in varied fields such as chemistry, biology, physics, and so on [1][2][3][4][5][6][7][8][9]. Many physicochemical properties of substances are determined by hydrogen bond interaction [10][11][12][13].…”