Raman spectroscopic investigation of the antimalarial agent mefloquine
- 200 Downloads
The antimalarial agent mefloquine was investigated using Fourier transform near-infrared (FT NIR) Raman and FT IR spectroscopy. The IR and Raman spectra were calculated with the help of density functional theory (DFT) and a very good agreement with the experimental spectra was achieved. These DFT calculations were applied to unambiguously assign the prominent features in the experimental vibrational spectra. The calculation of the potential energy distribution (PED) and the atomic displacements provide further valuable insight into the molecular vibrations. The most prominent NIR Raman bands at 1,363 cm−1 and 1,434 cm−1 are due to C=C stretching (in the quinoline part of mefloquine) and CH2 wagging vibrations, while the most intense IR peaks at 1,314 cm−1; 1,147 cm−1; and 1,109 cm−1 mainly consist of ring breathings and δCH (quinoline); C–F stretchings; and asymmetric ring breathings, C–O stretching as well as CH2 twisting/rockings located at the piperidine moiety. Since the active agent (mefloquine) is usually present in very low concentrations within the biological samples, UV resonance Raman spectra of physiological solutions of mefloquine were recorded. By employing the detailed non-resonant mode assignment it was also possible to unambiguously identify the resonantly enhanced modes at 1,619 cm−1, 1,603 cm−1 and 1,586 cm−1 in the UV Raman spectra as high symmetric C=C stretching vibrations in the quinoline part of mefloquine. These spectroscopic results are important for the interpretation of upcoming in vitro and in vivo mefloquine target interaction experiments.
KeywordsUV resonance Raman Raman spectroscopy Malaria Mefloquine Density functional theory calculation (DFT)
The authors gratefully acknowledge support from the Fonds der Chemischen Industrie and the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 630 “Recognition, Preparation, and Functional Analysis of Agents Against Infectious Diseases”, project C1). We thank Karla Schenzel for the possibility to use the FT NIR Raman spectrometer. Mefloquine was a kind gift from Roche Diagnostic GmbH.
- 9.MJ Frisch, GW Trucks, HB Schlegel, GE Scuseria, MA Robb, JR Cheeseman, JA Montgomery Jr, T Vreven, KN Kudin, JC Burant, JM Millam, SS Iyengar, J Tomasi, V Barone, B Mennucci, M Cossi, G Scalmani, N Rega, GA Petersson, H Nakatsuji, M Hada, M Ehara, K Toyota, R Fukuda, J Hasegawa, M Ishida, T Nakajima, Y Honda, O Kitao, H Nakai, M Klene, X Li, JE Knox, HP Hratchian, JB Cross, C Adamo, J Jaramillo, R Gomperts, RE Stratmann, O Yazyev, AJ Austin, R Cammi, C Pomelli, JW Ochterski, PY Ayala, K Morokuma, GA Voth, P Salvador, J Dannenberg, VG Zakrzewski, S Dapprich, AD Daniels, MC Strain, O Farkas, DK Malick, AD Rabuck, K Raghavachari, JB Foresman, JV Ortiz, Q Cui, AG Baboul, S Clifford, J Cioslowski, BB Stefanov, G Liu, A Liashenko, P Piskorz, I Komaromi, RL Martin, DJ Fox, T Keith, MA Al-Laham, CY Peng, A Nanayakkara, M Challacombe, PM W Gill, B Johnson, W Chen, MW Wong, C Gonzalez, JA Pople (2004) Gaussian 03, Revision C 02. Gaussian, Wallingford CT, Google Scholar
- 11.McHale JL (2002) In: Chalmers JM, Griffiths PR (eds) Handbook of vibrational spectroscopy, vol 1. Wiley, Chichester (and refs cited therein)Google Scholar
- 13.Perdew JP, Wang Y (1992) Phys Rev B45:13244; Perdew, JP, Chevary JA, Vosko, SH Jackson, KA, Pederson MR, Singh DJ, Fiolhais C (1992) Phys Rev B46:6671Google Scholar
- 15.Lee C, Yang W, Parr RG (1988) Phys Rev B37:785Google Scholar
- 16.Pople JA, Schlegel HB, Krishnan R, Defrees DJ, Binkley JS, Frisch MJ, Whitside RA (1981) Int J Quantum Chem Quant Chem Symp 15:269–278; MJ Frisch, JA Pople, JS Binkley (1984) J Chem Phys 80(7):3265–3269 (and refs therein); Hehre WJ, Stewart RF, Pople JA (1969) J Chem Phys 51(6):2657–2664 (and refs cited therein)Google Scholar
- 17.Bright E, Wilson, JR (1941) J Chem Phys 9:76–84; Wilson E Jr (1939) J Chem Phys 7:1047–1052; Wilson EB, Decius JC, Cross PC (1955) Molecular vibrations. McGraw-Hill, New YorkGoogle Scholar
- 18.Martin JML, Van Alsenoy C (1995) GAR2PED. University of AntwerpGoogle Scholar
- 37.Halls MD, Velovski J, Schlegel HB (2001) Theor Chem Ac 105:43–421Google Scholar
- 38.Olivaro PL, Goldberg DE (1995) Parasit Today 11(8):294–297; Hawley SR, Bray PG, O’Neill PM, Park BK, Ward SA (1996) Biochem Pharmacol 52:723–733; Yayon A, Cabantchik ZI, Ginsburg H (1984) EMBO J 3(11):2695–2700 ; Ginsburg H, Geary TG (1987) Biochem Pharmacol 36(10):1567–1576Google Scholar