Structural analysis of the antimalarial drug halofantrine by means of Raman spectroscopy and density functional theory calculations

The structure of the antimalarial drug halofantrine is analyzed by means of density functional theory (DFT) calculations, IR, and Raman spectroscopy. Strong, selective enhancements of the Raman bands of halofantrine at 1621 and 1590 cm(-1) are discovered by means of UV resonance Raman spectroscopy with excitation wavelength lambda(exc) = 244 nm. These signal enhancements can be exploited for a localization of small concentrations of halofantrine in a biological environment. The Raman spectrum of halofantrine is calculated by means of DFT calculations [B3LYP/6-311 + G(d,p)]. The calculation is very useful for a thorough mode assignment of the Raman bands of halofantrine. The strong bands at 1621 and 1590 cm(-1) in the UV Raman spectrum are assigned to combined C=C stretching vibrations in the phenanthrene ring of halofantrine. These bands are considered as putative marker bands for pi pi interactions with the biological target molecules. The calculation of the electron density demonstrates a strong distribution across the phenanthrene ring of halofantrine, besides the electron withdrawing effect of the Cl and CF3 substituents. This strong and even electron density distribution supports the hypothesis of pi pi stacking as a possible mode of action of halofantrine. Complementary IR spectroscopy is performed for an investigation of vibrations of polar functional groups of the halofantrine molecule. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3432656]