Dicoumarol and related coumarin compounds are potent inhibitors of oxidoreductase NQO1, an enzyme overexpressed in several types of solid tumour. Using density function theory, we study dicoumarol conformation in various tautomeric and ionisation states, in the gas phase and low and high dielectric environments. In aqueous solution, where the monoanionic form of dicoumarol is predominant, we predict a syn rotamer as favoured, which is the conformation crystallographically observed bound to NQO1. Comparison of internal distortion energies and protein docking calculations rationalise why only the syn form is found bound to NQO1. (C) 2014 Elsevier B.V. All rights reserved.