Tautomerism and spectroscopic properties of the immunosuppressant azathioprine

• The relative stability of AZA tautomers are calculated by DFT/B3LYP method.
• The calculated vibrational spectra are well correlated with the experimental data.
• Solvent effect on the electronic spectra of AZA is calculated by TD-DFT method.
• The calculated NMR spectra of all tautomers are compared with experimental data.

The molecular structure and the relative stabilities of the four possible tautomers of the immunosuppressant azathioprine (AZA) are calculated by DFT/B3LYP method using different basis sets. The results of the energy analysis and thermodynamic treatment of the obtained data are used to predict the relative stabilities of the AZA tautomers. The effect of solvents such as DMSO and water on the stability of the AZA tautomers was studied using the polarized continuum method (PCM) at the same level of theory. The calculation predicted that, the total energies of all tautomers are decreased indicating that all tautomers are more or less stabilized by the solvent effect. The vibrational spectra of AZA are calculated using the same level of theory and the results are compared with the experimentally measured FTIR spectra. Good correlation is obtained between the experimental and calculated vibrational frequencies (R2 = 0.997). The electronic spectra of AZA in gas phase and in methanol as solvent are calculated using the TD-DFT method. The calculations predicted bathochromic shift in all the spectral bands in presence of solvent compared to the gas phase. Also the NMR spectra of all tautomers are calculated and the results are correlated with the experimental NMR chemical shifts where the most stable tautomer gives the best correlation coefficient (R2 = 0.996).

The optimized molecular structure (left) and the molecular electrostatic potentials (right) mapped on the electron density surface calculated by the DFT/B3LYP method for the tautomer T2 of AZA.Figure optionsDownload as PowerPoint slide