Hydroxyquinol (1,2,4-trihydroxybenzene) exhibits a variety of activities of interest to the biomedical and organic chemist. In the particular, hydroxyquinol has numerous possible non-equivalent sites for protonation and reaction with other electrophiles. High level DFT and conventional ab initio quantum chemical calculations, diverse isodesmic proton transfer reactions, and qualitative understanding, of both intramolecular hydrogen bonding and carbocation stability, are used to explain the energy and geometry changes, and the location (which carbon or oxygen) associated with the still unmeasured proton affinity and gas-phase basicity of this species. Application is made to the synthesis of still unknown calixarenerelated macrocycles. (C) 2013 Elsevier Ltd. All rights reserved.