A Computational Study of the Effects of Different Solvents on the Characteristics of the Intramolecular Hydrogen Bond in Acylphloroglucinols

Abstract

Acylphloroglucinols are a broad class of compounds, derivatives from 1,3,5-trihydroxybenzene, and exhibiting a variety of biological activities. They are characterized by the presence of at least one COR group, whose sp(2) O can form an intramolecular hydrogen bond with a neighboring phenolic OH. This H-bond plays dominant roles in determining conformational preferences and energy, and is expected to play significant roles in biological activity mechanisms, which strongly motivates the study of its characteristics in solution. A computational study of a representative number of actual and model structures with different R was carried out in three solvents with different polarities and different types of interactions with solute molecules: water, acetonitrile, and chloroform, utilizing the PCM model. Calculations were mostly performed at the HF/6-31G(d,p) level because of affordability reasons in view of the size and number of the structures considered (the smallest structures were also calculated at MP2/6-31+G(d,p) level). Comparison with the results of a previous study in vacuo shows similar patterns within each medium, pointing to similarities in the influence of relevant geometry factors on the characteristics of the H-bond. The medium appears to have little influence on the parameters of the H-bond. Comparison across media of the energy increase on H-bond removal (an indication of the H-bond strength) is complicated by the greater solvent stabilization of the conformer resulting from H-bond removal, with respect to the one in which the H-bond is present. Several factors, however, would point to a strength not too different from that observed in vacuo.

Conformational, electronic and antioxidant properties of lucidone, linderone and methyllinderone: DFT, QTAIM and NBO studies

“…IHBs have significant roles in stabilising molecular conformations and in influencing biological activities [49][50][51][52][53][54][55][56][57][58][59][60][61]. LD and LR have two conformations (LD t -1a and LD t -1b, and LR t -1a and LR t -1b, respectively) that are stabilised by the presence of IHB, resulting in the formation of H-bond quasi-rings.…”

Computational study of the patterns of weaker intramolecular hydrogen bonds stabilizing acylphloroglucinols

“…Their many diverse biological activities make ACPLs interesting for drug development 1. This work pertains to a systematic computational study of ACPLs, aimed at identifying patterns in their conformational preferences and the factors influencing them,2a–c so as to obtain information that can be useful for drug design, for example, for the search of molecular structures strengthening the pharmacological properties of natural ACPLs. For this purpose, that is, to enable realistic predictions on other ACPLs structures, the information obtained from this study needs to be as detailed as possible with reference both to general patterns and to specific subsets of compounds.…”

“…The structure on the right shows more detailed numbering of the H atoms in R and R′ that might be involved in unconventional CH···O IHBs (for longer R or R′ than those shown here, one of the H atoms is replaced by a C atom). The atom numbering is similar to that of other works of ours on ACPLs2a,b,d for consistency reasons and to facilitate comparisons.…”

“…The sp 2 O of the AC can form an intramolecular hydrogen bond (IHBs) with an ortho OH, that we termed “first IHBs”; it characterizes nearly all ACPLs, plays a dominant role in determining conformational preferences and is present in all populated conformers both in vacuo and in solution 2a–c. Other IHBs play significant roles in determining preferences among different conformers in which the first IHBs is present.…”

Enthalpy–entropy relations in the acid–base equilibrium of warfarin and 10-hydroxywarfarin; joint experimental and theoretical studies

“…In particular, we wanted to evaluate the contribution of specic intramolecular interactions to dissociation thermodynamics, [18][19][20][21][22][23][24] and check, whether manipulations in solvent composition by addition of different modiers: surfactant and cosolvent, affect dissociation enthalpy and entropy. We have also used 7-hydroxywarfarin (W7) as the reference compound, to verify whether and how hydroxylation site has any impact on dissociation thermodynamics.…”