Structural Analysis of the Anti-Malaria Active Agent Chloroquine under Physiological Conditions
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- 作者：Torsten Frosch ; Michael Schmitt ; Gerhard Bringmann ; Wolfgang Kiefer ; Jü ; rgen Popp
- 刊名：Journal of Physical Chemistry B
- 出版年：2007
- 出版时间：February 22, 2007
- 年：2007
- 卷：111
- 期：7
- 页码：1815 - 1822
- 全文大小：310K
- 年卷期：v.111,no.7(February 22, 2007)
- ISSN：1520-5207
文摘
UV resonance Raman spectroscopy was applied for a selective enhancement of molecular vibrations of theimportant antimalarial chloroquine under physiological conditions. The resonance Raman spectra of chloroquineat pH values resembling the pH value of blood and the pH value of the acid food vacuole of plasmodium canunambiguously be distinguished via Raman resonantly enhanced mode at 721 cm-1. These vibrations areassigned to -(CH2)n- rocking mode of the chloroquine side chain and are expected to be influenced byprotonation of chloroquine. Furthermore, vibrations belonging to the quinoline ring (important for 
--interactions to hemozoin) are resonantly enhanced and can be studied selectively. A convincing modeassignment was performed by means of DFT calculations. These calculations proved that the differentprotonation states of chloroquine remarkably influence various vibrational modes, the molecular geometry,and molecular orbitals. The presented results are of significant relevance for a Raman spectroscopicallocalization of chloroquine inside the acid food vacuole of plasmodium, the study of --interactions ofchloroquine to the biological target molecules hematin and hemozoin and the protonation state of chloroquineduring this docking process. The protonation of the weak base chloroquine is considered to be crucial for anaccumulation inside the acid food vacuole of plasmodium and an object for resistances against this drug.
--interactions to hemozoin) are resonantly enhanced and can be studied selectively. A convincing modeassignment was performed by means of DFT calculations. These calculations proved that the differentprotonation states of chloroquine remarkably influence various vibrational modes, the molecular geometry,and molecular orbitals. The presented results are of significant relevance for a Raman spectroscopicallocalization of chloroquine inside the acid food vacuole of plasmodium, the study of --interactions ofchloroquine to the biological target molecules hematin and hemozoin and the protonation state of chloroquineduring this docking process. The protonation of the weak base chloroquine is considered to be crucial for anaccumulation inside the acid food vacuole of plasmodium and an object for resistances against this drug.