Molecular conformations and harmonic force field of 1,3,5-benzenetriol molecule from ab initio and density functional theory investigations

2012

Acylphloroglucinols are a broad class of phloroglucinol derivatives characterized by the presence of a COR group, where R is more often an alkyl chain. They are largely present in natural sources and exhibit a variety of biological activities, including antibacterial, antiviral, antifungal, antitumor, antioxidant, and antimalarial. This work reports the results of a systematic conformational study (in vacuo, chloroform, acetonitrile, and water) of a representative number (118) of actual and model acylphloroglucinol structures, considering the most common R chains and investigating conformational preferences and relative energies as well as the influence of specific structural features characterizing significant subsets of compounds. The study aimed at identifying patterns for conformational preferences and at singling out the conformational aspects more closely related to the individuality of different structures, as these are expected to be more closely linked to the differences in the biological activities of different compounds. The results highlight patterns enabling reliable predictions of the conformational preferences of acylphloroglucinol molecules.

Section: Calculations and Resultssupporting

confidence: 58%

“…2) or nonuniform. For the parent compound,18 the former corresponds to C 3h symmetry and has ≈1 better energy with all methods 12(i). The effect is maintained in ACPL and also in other phloroglucinol derivatives 12(e)…”

Section: Calculations and Resultsmentioning

confidence: 95%

The conformational preferences of acylphloroglucinols—a promising class of biologically active compounds

2012

“…The energy of w/r pairs differs significantly only for those cases (FA‐2, FA‐3, and FA‐4) when one of the two forms corresponds to uniform mutual orientation of the three phenolic OH (Fig. 4), thus extending to FA the preference for uniform orientation shown by the parent compound 58 and other phloroglucinol derivatives 13(a,d). The estimation of the stabilization associated with uniform orientation is close with all the methods (1.1–1.6/MP++, MP, 1.1–1.7/HF++, HF, and 1.0–1.5/DF++, DF) and is slightly higher than for the parent compound (1.0 58).…”

Section: Results Of Calculations In Vacuomentioning

confidence: 97%

“…4), thus extending to FA the preference for uniform orientation shown by the parent compound 58 and other phloroglucinol derivatives 13(a,d). The estimation of the stabilization associated with uniform orientation is close with all the methods (1.1–1.6/MP++, MP, 1.1–1.7/HF++, HF, and 1.0–1.5/DF++, DF) and is slightly higher than for the parent compound (1.0 58). Ascribing it to the mutual orientation of the phenolic OH is consistent with the finding 21 that a para OH has no noticeable influence on the COOH geometry preferences, what excludes that it might be ascribed solely to the orientation of H17.…”

Section: Results Of Calculations In Vacuomentioning

confidence: 98%

A computational study of the carboxylic acid of phloroglucinol in vacuo and in water solution

2009

2,4,6-Trihydroxybenzoic acid (FA) is the carboxylic acid of phloroglucinol and, in turn, the parent compound of many biologically active compounds. The biological activities of FA are "extreme" among trihydroxybenzoic acids (e.g., lowest antioxidant activity, highest toxicity toward crustaceans). A complete MP2/6-31ϩϩG(d,p) conformational study in vacuo shows that the lowest energy conformers contain two intramolecular hydrogen bonds between the COOH function and the two ortho phenolic OH, with the Z form of COOH preferred over the E form. Comparisons with conformers in which the H-bonds are removed enable fairly reliable evaluations of their energy, because of an off-plane shift of COOH on H-bond removal, decreasing the effects of lone pair repulsion. Comparisons with the other hydroxybenzoic acids (extensively calculated in vacuo at the same level of theory) suggest that FA has the strongest intramolecular H-bonds. PCM calculations of FA in water solution show the same sequence of relative stabilities as in vacuo, with narrower differences because of the greater solvent stabilization of higher energy conformers. Calculations of adducts with water molecules H-bonded to different donor-acceptor centers of FA show the preferred arrangements of water molecules around the different regions of FA and confirm that the stronger intramolecular H-bonds are not broken on competition with the possibility of formation of intermolecular H-bonds. HF/6-31ϩϩG(d,p) calculations of adducts, in which the FA molecule is completely surrounded by water molecules, show that 14 -16 water molecules (depending on the FA conformer geometry) realize arrangements corresponding to a presumable first solvation layer, with all the water molecules directly H-bonded to donor-acceptor centers of FA or bridging water molecules directly H-bonded to them.

“…Hindrances with the methyl at C5 make the situation slightly less favorable for H29 in the r cases and for H26 when it is oriented downwards, and the H‐bond angle becomes 149°–153° (Y‐d‐r–A and Y‐s‐w–A▸). When H25 or H26 are oriented upwards and not engaged in the first H‐bond (u‐conformers), their accessibility is limited because of the isopropyl group: on bonding to a water molecule, the OH group deviates considerably from planarity (44.3° for Y‐d‐r‐u–A▾♦ and 41.6° for Y‐s‐w‐u–A▸♦), what favors the interaction between the OH group and the water molecule (by decreasing hindrances with the isopropyl group), but not the total energy of the adduct, as nonplanar orientations of the OH groups are unfavorable for the parent compound 16 and for the phloroglucinol moiety in caespitate 4.…”

Section: Adducts Of the Caespitate Molecule With Water Moleculesmentioning

confidence: 99%

A computational study of the interactions of the caespitate molecule with water

2008

ABSTRACT:The water solvent effects on the caespitate molecule-an acylated and prenylated phloroglucinol of natural origin exhibiting antibacterial and antifungal activities-are investigated both as bulk effects and considering explicit water molecules H-bonded to its donor and acceptor centers. All calculations are performed at HF/6-31G(d,p) level and the bulk effect of the solvent is calculated with the PCM method. PCM calculations without explicit water molecules show a change in the relative energy pattern, for which the five lowest energy conformers have only the intramolecular hydrogen bond involving the carbonyl O atom of the acyl chain and one of the neighboring OH groups of the phloroglucinol moiety (first H-bond), whereas in vacuo, the 24 lowest energy conformers (accounting for practically all the population) have also the intramolecular hydrogen bond (second H-bond) involving an O atom of the ester function (with which the prenyl chain ends) and one of the neighboring OH groups of the phloroglucinol moiety. Calculations with explicit water molecules show that the first intramolecular H-bond is mostly maintained, whereas the second H-bond is not maintained on competition with intermolecular H-bonds with water molecules. Preferred geometrical arrangements of water molecules around the caespitate molecule are identified and the effects, on such geometrical preferences, of the presence of the two substituent chains are highlighted by comparison with the adducts of the parent compound.