In vitro polarization-resolved resonance Raman studies of the interaction of hematin with the antimalarial drug chloroquine

Despite the public health impact of human malaria, the mechanism of hemozoin inhibition by antimalarial drugs such as chloroquine (CQ) is not yet fully understood. Polarization-resolved resonance Raman spectra of hematin and its complex with CQ were recorded under Q-band resonance conditions in order to monitor the binding of the 4-aminoquinoline drug to the heme macrocycle. Upon drug addition, only wavenumber shifts smaller than 2 cm(-1) are detected, indicating a non-covalent interaction in the electronic ground state of the drug-target complex. The decreased resonance Raman intensity of the anomalously polarized mode v(19)(a(2g)) in the perpendicular polarized spectrum of the complex suggests changes of the excited-state geometry along the corresponding normal coordinate. Copyright (C) 2004 John Wiley Sons, Ltd.