Normal-mode analysis of the Raman-active modes of the anti-tumor agent 6-mercaptopurine

Abstract

The Raman spectra of the antitumor agent 6‐mercaptopurine (6MP) in the solid and solution state were recorded in the 600–1700 cm−1 spectral region. The normal modes of 6MP were calculated using a Urey–Bradley empirical force field (UBFF) and with the PM3 semi‐empirical method. Prior to performing the normal‐mode calculations on 6MP, similar calculations were performed on methanethiol and thiophenol. The force constant parameters obtained from these calculations were then transferred to the 6MP calculations. The results of the normal‐mode calculations were compared with the observed spectra and an assignment of the vibrational modes is proposed. Based on changes in the wavenumbers of the Raman spectra between the solution and solid form 6MP and on normal‐mode calculations, it is proposed that in the solid form 6MP crystallizes in the tautomer form whereas in solution the molecule ionizes by losing the hydrogen at the N‐1 position. Copyright © 2000 John Wiley & Sons, Ltd.

Vibrational assignments and electronic structure calculations for 6‐thioguanine

“…[4] Normal modes of 6-mercaptopurine were studied using Raman spectra and theoretical calculations were made using Urey-Bradley empirical force field (UBFF) and PM3 methods. [5] To the best of our knowledge there is no work reported on complete vibrational assignment using DFT with higher computational methods.…”

Assignment of the Raman‐active modes of the antitumor agent azathioprine by normal‐mode calculations

“…Inverting the normal modes of the 1210 and 1192 cm 1 bands of AZA is consistent with what was observed for 6MP. 15 The PM3 calculation reproduced the relative shifts for both wavenumbers without any inversion.…”

“…The procedure which was employed in this study is similar to that used in calculating the normal modes of 6MP. 14,15…”

“…In previous work, our group investigated the mode of interaction between 6MP and a silver surface employing the surface selection rules developed for surface-enhanced Raman spectroscopy. 14,15 Surface-enhanced Raman scattering spectroscopy (SERS) has been established as an effective surface probe for providing structural information on the orientation of molecules adsorbed on an electrode surface, the nature of the adsorbate surface bond and the effect of the electrode potential on these features. 16 A prerequisite for the utilization of SERS in the determination of molecular orientation is the assignment of bands in the Raman spectrum to fundamental vibrational modes of the molecule.…”

<title>Surface-enhanced Raman scattering (SERS): nanoimaging probes for biological analysis</title>

“…Using spatially localized Raman spectroscopy measurements it has been possible to 1) determine the molecular composition of calcium salts, cholesterol, proteins, and lipids in artery walls, distinguishing between normal and diseased tissue 1 , 2) to detect basal cell carcinoma 2 through the presence of a protein expressed in diseased and not healthy tissues, and 3) determine the structure of 6-mercaptopurine (6MP) (a commonly used antineoplastic and tumor growth inhibiting drug) in aqueous and solid states. 3 Raman spectroscopy is a widely used and well-suited technique for the determination of molecular structure, multicomponent qualification, and quantitative analysis 4 in biological samples. Raman spectroscopy permits accurate, realtime, nondestructive, non-invasive measurements to take place under cellular physiological conditions producing a well characterized unique chemical fingerprint spectrum of the analyte.…”