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

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 sp² 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 sp² 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 whichthe water molecules directly H‐bonded to the central molecule are bridged by other water molecules, to approximate a continuous layer. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2378–2390, 2010