Blue shifted C-H stretch vibrations caused by C-H center dot center dot center dot O intramolecular improper hydrogen bonds in zidovudine (or AZT) conformers are employed to differentiate its conformers. Two sugar-sugar C-H center dot center dot center dot O-(5') improper hydrogen bonds, existing in conformers of AZT with apparent drug potency, are related to their unique sugar puckering, showing C-(3')-exo or -endo orientations. Aqueous solution causes a global red shift in IR spectra, but remains reduced blue shifted C-H stretch frequencies. Molecular electrostatic potentials (MEPs) of the conformers and orbitals such as 40a of AZT-B and 37a of AZT-C, which are found to be responsible for the intramolecular improper hydrogen bonds, are also given in this study. (C) 2010 Elsevier B. V. All rights reserved.