Adducts of acylphloroglucinols with explicit water molecules: Similarities and differences across a sufficiently representative number of structures

Abstract

Acylphloroglucinols constitute a broad class of compounds, derivatives of 1,3,5-trihydroxybenzene, characterized by at least one COR group and exhibiting a variety of biological activities. The presence of several hydrogen bond donor or acceptor sites (the three phenol OH of the phloroglucinol moiety and the sp 2 O of the COR group), and their comparatively close spacing, makes the study of adducts with explicit water molecules particularly interesting, because it is possible to consider adducts in which water molecules surround the entire acylphloroglucinol molecule, or a large part of it, providing expectedly realistic images of possible arrangements of water molecules in the close vicinity of the acylphloroglucinol molecule in the aqueous medium. This work considers a number of different monomeric structures sufficiently representative of the broad structural variety of acylphloroglucinols and considers adducts of all the relevant conformers for each structure. Calculations use the HF/6-31G(d,p) level because of affordability reasons in view of the adducts' size. The results: show that the intramolecular hydrogen bond (IHB) between the sp 2 O of COR and an ortho OH does not break on competition with solute-solvent intermolecular H-bonding; highlight general trends and trends related to specific geometry features of the conformers; enable an interpretation of the additional solvent stabilization of the conformers without IHBs, observed from polarizable continuum model results in water solution; and highlight the significance, for this class of compounds, of considering adducts in which the water molecules directly H-bonded to the central molecule are bridged by other water molecules, to approximate a continuous layer.

Intramolecular Hydrogen Bonding and Conformational Preferences of Arzanol—An Antioxidant Acylphloroglucinol

“…The results in solution are also consistent with the trends identified for ACPLs [ 8 , 42 ] and suggest that the first IHB and most of the IMHBs do not break in a water solution. A separate study of adducts of arzanol with explicit water molecules is planned to verify this inference.…”

“…All the other values suggest that the other IHBs are maintained in water solution. Previous studies on ACPLs [ 8 , 42 ] suggest that the first IHB is maintained in solution, including water solution. As for the IMHBs of ARZ, their permanence is suggested not only by their parameters in solution, but also by the fact that the geometry of several conformers does not favour solvent molecules’ access to the atoms forming them.…”

Antioxidant Radical Scavenging Properties of Phenolic Pent-4-En-1-Yne Derivatives Isolated FromHypoxis Rooperi. A DFT Studyin vacuoand in Solution

“…IHB are known to influence both conformational preferences and physico-chemical properties, which in turn influence bioactivities. [25][26][27][28][29][30][31][32][33][34][35][36] A study of the hypoxoside molecule with its two glucose moieties is computationally unaffordable; therefore, each glucose moiety was substituted with a methyl group, with the aim of reducing computational cost; this model structure will be denoted by the acronym HYP. As reported earlier by other researchers, it is very unlikely that the glucose moiety may have some influence on the reactivity of the systems, because the reactive site is universally accepted to be the phenolic ring.…”

Correlation Effects in Trimeric Acylphloroglucinols

“…This makes accurate computational studies of biologically active molecules particularly important for subsequent steps of drug design. The present work pertains to a systematic computational study of ACPLs, investigating a number of aspects: the main factors stabilising the molecules of monomeric ACPLs (M-ACPLs) in vacuo [5][6][7][8] and in solution (e.g., [9,10]); the molecular properties of dimeric ACPLs (D-ACPLs, whose molecules contain two ACPL monomers) as a subclass of ACPLs [11]; and the molecular properties of a number of ACPLs with specific activities or specific structural features. 2), the R^ of the first monomer, the R* of the third monomer, and both R^ and R* of the inner monomer, are replaced by methylene bridges.…”

“…They are dispersive in nature and, therefore, they can be taken into account only by computational These studies clearly highlighted features related to the acylphloroglucinol unit and, therefore, appearing in all ACPL molecules (besides specific features associated with functions that may be present in the R* or Rˆsubstituents). The general features comprise the dominant role of the intramolecular hydrogen bond (IHB) between the sp 2 O of the acyl group and a neighbouring phenol OH (termed 'first IHB') [5][6][7]10,11], and the nonnegligible influence of the orientation of the phenol OHs [6,7,12] and of the weaker C-H•••O IHBs [8].…”