Estimation of the Intramolecular O–H···O═C Hydrogen Bond Energy via the Molecular Tailoring Approach. Part I: Aliphatic Structures

Abstract

A simple and universal method for the estimation of the intramolecular hydrogen bond (HB) energy (E(HB)) in hydroxycarbonyl aliphatic compounds is proposed by the application of the molecular tailoring approach (MTA) based on calculations at the second-order Møller-Plesset MP2 level. The calculation of EHB can be realized by the one optimization and three single point calculations of the energy for each compound with carbonyl and hydroxyl groups involved in HB. The intramolecular hydrogen bond energies estimated for 153 structures (of 102 compounds) ranged from 1.4 to 13.7 kcal/mol for systems without resonance-assisted hydrogen bonding (RAHB). To verify the method, we show the correlations of the energy (E(HB)) in six-, seven-, and eight-membered HB rings in the optimized multifunctional molecules with the usual geometry descriptors of hydrogen bonds. Moreover, topological parameters from the atoms in molecules (AIM) theory and the calculated infrared and proton NMR spectra are correlated. The effects of conjugation and π-electron delocalization, bifurcation, and cooperativity are discussed, along with the correlation between the strength and geometrical parameters of H bonding.

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

“…The energy of intermolecular interactions is simply measured as a difference between the energies of a H-bonded structure and its components. This approach cannot be used to study intramolecular interactions, and despite the fact that the hydrogen bonds are qualitatively well understood, [18,122,124,125,183] it is generally admitted that a simple method of calculation and quantitative data is needed [184]. The energy of such optimized structures stabilized by the intramolecular hydrogen bond was used to estimate its strength by different comparative methods: cis−trans analysis [132,185,186], isodesmic reactions [187] and conformational analysis with gradual or total rotation of the H-bond donor or acceptor [138,188,189].…”

“…These results not only indicate the predictive power of this method but also shed light on factors that determine the magnitude of experimentally measured hydrogen-bonding constants for different acceptors with respect to a given donor, suggesting a primarily enthalpic contribution from hydrogen-bonding energy. The method can be used for evaluating the effects of steric interference and inhibitor binding geometry on hydrogen-bonding strength in drug design [184].…”

“…Importantly, even the subtle structural and stereoelectronic effects are well reflected by the hydrogen bond relative energies. Moreover, Rusinska-Roszak et al [184] show that when the molecules become more complex or the number of intramolecular hydrogen bonds increases (including the cooperative H bond phenomenon) the presented exhaustive stereoelectronic effects interpretation may still be accessible.…”

Topological insights into the 1/1 diacetyl/water complex gained using a new methodological approach

“…Indeed, from a geometric point of view, the distances X-H and H…Y as well as the direct angle X-Ĥ…Y are needed to characterize the hydrogen bond between a donor atom X and an acceptor atom Y [13]. For intermolecular interactions, the energy associated with hydrogen bonding can be calculated as the difference in energy between the complex and the isolated isomers 1 [14]. Decomposition of this interaction energy into the electrostatic interaction energy, the exchange repulsion energy, and the delocalization and correlation energies-as done in a symmetry-adapted perturbation theory (SAPT) analysiscan provide some insight into the nature of the interaction [15,16].…”

“…For a discussion of how the energies of intramolecular hydrogen bonds can be estimated, see for example[14].…”