The fundamental nature and importance of electrostatic potential in hydrogen bond formation: a case study of heterocycles frequently observed in drugs

Abstract

Molecular electrostatic potential (MESP) analysis is employed to predict the hydrogen bond (HB) interaction strength (Eint) of frequently encountered chemical motifs (CO‾‾‾HC, CN‾‾‾HN, CN‾‾‾HC, CF‾‾‾HC, and CN‾‾‾OC) in commonly observed...

Quantifying the hydrogen-bond propensity of drugs and its relationship with Lipinski's rule of five

“…In our prior studies, we successfully forecasted hydrogen bond strengths between water and various chemical motifs, utilizing reference molecules representing each motif, selected for their simplicity and appropriateness. 38,42 Fig. 1 shows twenty ring molecules, each incorporating distinct chemical motifs such as CO — HC, CO — HN, N — HC, CN — HN, F — HC, N — OC, Br — HC, S — HC, etc.…”

“…33 Utilizing the outer contour of electronic density in conjunction with MESP parameters is an approach to elucidate the properties of non-covalent interactions across various studies. 34–39 Politzer et al revealed that the computed electrostatic potentials for aqua metal complexes offer valuable insights into the strength of hydrogen bonds. 40 Zarić et al employed accurate quantum chemical calculations to evaluate the strength of hydrogen bond interactions in coordinated ethylenediamine.…”

“…41 Very recently, Haritha and Suresh have conducted quantification of hydrogen bond strength between water and various chemical motifs (OC–NH, FC–CH, OC–CH, N–CO, N–C–NH, N–CH) frequently encountered in rings in drugs, and the findings indicate that variation in the MESP at the nuclei, Δ V n , of interacting atoms within each motif plays a pivotal role in predicting the strength of these hydrogen bond interactions. 38,42 In the ring molecule, the ordered pairs of (Δ V n of heteroatom, Δ V n of H atom) exhibited variations of (+, +), (+, −), (−, +), and (−, −) compared to a reference molecule. The (−, +) MESP behaviour consistently enhanced the (ring)heteroatom⋯H w and O w ⋯H(ring) interactions, while the (+, −) behaviour weakened these interactions.…”

Ferulic Acid Dimers as Potential Antiviral Agents by Inhibiting TMV Self-Assembly

“…44 Surprisingly, compound A6 had eight HBAs (no more than 10) and four HBDs (no more than five), which complied with the Ribinski rule. 45 Therefore, compound A6 can be used as a promising candidate for the development of new antiviral drugs targeting TMV CP. TEM Determination of Compounds to TMV.…”