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

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. (c) 2008 Wiley Periodicals, Inc.