Nine biologically active theophylline derivatives were investigated using quantum chemical methods (density functional theory level). All calculations were performed at B3LYP/6-31G** level of theory. The electrostatic potential charges, highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) gap, dipole moment, vibration frequencies, and electronic spectra were calculated. Log P was determined by Ghose-Crippen method. All of the compounds under study are polar and negatively charged, which is necessary for their interaction with the receptors/enzymes. Majority of the compounds are lipophilic and they can easily diffuse through the cell membrane. The observed differences between the calculated and the experimental vibration frequencies in the Fourier Transform Infrared Spectroscopy (FTIR) spectra are established to be mainly in NH and OH bands, due to hydrogen bonds formation. The discrepancies between theoretical and experimental electronic spectra may be due to vibration effects and H-bonding with the solvent molecules. The obtained results show that this type of spectrum is formed mainly by the xanthine fragment of the molecule, especially in the fingerprint region. All calculated properties could be useful for future qualitative-structure activity relationship (QSAR) analysis. © 2012 Wiley Periodicals, Inc.