The role of additional O-H•••O intramolecular hydrogen bonds for acylphloroglucinols' conformational preferences in vacuo and in solution

Acylphloroglucinols (ACPLs) are phloroglucinol derivatives characterised by the presence of a COR group and exhibiting a variety of biological activities, making them potentially interesting for drug development. The structural variety of these compounds prompts specific studies of relevant features characterising significant subsets of compounds. One of the more interesting features is the presence, in various structures, of additional intramolecular hydrogen bonds (IHBs), besides the one between the sp(2) O of COR and an ortho phenol OH, which characterises all ACPLs. This work studies the geometric characteristics and the stabilising effects of additional O-H center dot center dot center dot O IHBs, considering a selection of structures representative of the more common possibilities for their formation and comparing the results in vacuo, chloroform, acetonitrile and water. The results highlight patterns depending on the types and positions of the atoms forming the additional IHBs and, for the results in solution, also on the nature of the solvent. The stabilising effects, important in vacuo, decrease with increasing solvent polarity. In water solution, the additional IHB breaks if its breaking makes a donor or acceptor group fully (no steric hindrances) available for solute-solvent intermolecular hydrogen bonds.