Morphology-sensitive Raman modes of the malaria pigment hemozoin.

Resonance Raman spectroscopy was applied for investigating the malaria pigment hemozoin, which is an important target structure of antimalarial drugs. Morphology-sensitive low wavenumber modes of hemozoin were selectively enhanced with help of excitation wavelengths at lambda = 633 nm and lambda = 647 nm. The assignment of the most prominent bands in the Raman spectra at 343 cm(-1) and 368 cm(-1) was assisted by DFT calculations of the hemozoin dimer. The mode at 343 cm(-1) in the Raman spectrum of hemozoin is strongly enhanced with lambda(exc.) = 647 nm and is represented by a combined, symmetric doming mode of the two hematin units in the hemozoin dimer. The enhancement of this vibration is stronger in the resonance Raman spectrum of hemozoin compared with less crystalline beta-hematin. The selective resonance enhancement of the morphology-sensitive Raman modes of hemozoin is caused by absorption bands in the UV-VIS-NIR spectrum. This absorption spectrum of the crystalline malaria pigment hemozoin shows a strong band at 655 nm. Another broad absorption band at 870 nm is the reason for the strong relative resonance enhancement of the mode at 1372 cm(-1) in the Raman spectrum of crystalline hemozoin with lambda(exc.) = 830 nm. In conclusion, resonance Raman micro-spectroscopy with lambda(exc.) = 647 nm was shown to have great potential as an analytical tool to probe the morphology of hematin samples.

[1]  T. Egan.  Haemozoin (malaria pigment): a unique crystalline drug target , 2003 .

[2]  D. Goldberg,et al.  An iron-carboxylate bond links the heme units of malaria pigment. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Roepe,et al.  Chloroquine resistance in the malarial parasite, Plasmodium falciparum , 2002, Medicinal research reviews.

[4]  M. Senge,et al.  The Malaria Pigment Haemozoin—A Focal Point of Action for Antimalarial Drugs , 2000, Chembiochem : a European journal of chemical biology.

[5]  Robert G. Ridley,et al.  Medical need, scientific opportunity and the drive for antimalarial drugs , 2002, Nature.

[6]  M. Schmitt,et al.  Device for Raman difference spectroscopy. , 2007, Analytical chemistry.

[7]  D. Goldberg,et al.  A Common Mechanism for Blockade of Heme Polymerization by Antimalarial Quinolines* , 1998, The Journal of Biological Chemistry.

[8]  M. Schmitt,et al.  In vitro polarization‐resolved resonance Raman studies of the interaction of hematin with the antimalarial drug chloroquine , 2004 .

[9]  J. Sachs,et al.  The economic and social burden of malaria , 2002, Nature.

[10]  P. Stephens,et al.  Phase homogeneity and crystal morphology of the malaria pigment β-hematin , 2002 .

[11]  D. Radzioch,et al.  Hemozoin Increases IFN-γ-Inducible Macrophage Nitric Oxide Generation Through Extracellular Signal-Regulated Kinase- and NF-κB-Dependent Pathways 1 , 2003, The Journal of Immunology.

[12]  R. Coppel,et al.  An alternative to serum for cultivation of Plasmodium falciparum in vitro. , 1997, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[13]  S. Hay,et al.  The global distribution of clinical episodes of Plasmodium falciparum malaria , 2005, Nature.

[14]  T. Egan,et al.  The mechanism of beta-hematin formation in acetate solution. Parallels between hemozoin formation and biomineralization processes. , 2001, Biochemistry.

[15]  D. S. Bohle,et al.  Synthesis of β-hematin by dehydrohalogenation of hemin , 1993 .

[16]  Jürgen Popp,et al.  In situ localization and structural analysis of the malaria pigment hemozoin. , 2007, The journal of physical chemistry. B.

[17]  K. Ang,et al.  Resonance Raman Microspectroscopy of Normal Erythrocytes and Plasmodium Berghei-Infected Erythrocytes , 1999 .

[18]  Don McNaughton,et al.  Resonance Raman spectroscopy in malaria research , 2006, Expert review of proteomics.

[19]  M. Schmitt,et al.  Raman spectroscopic investigation of the antimalarial agent mefloquine , 2007, Analytical and bioanalytical chemistry.

[20]  H. Matile,et al.  Malarial haemozoin/β-haematin supports haem polymerization in the absence of protein , 1995, Nature.

[21]  Han-Ru Zhu,et al.  AGGREGATION-ENHANCED RAMAN SCATTERING OF A CYANINE DYE IN HOMOGENEOUS SOLUTION , 1997 .

[22]  S. Ward,et al.  A Requiem for Chloroquine , 2002, Science.

[23]  J. Popp,et al.  Relationship between molecular structure and Raman spectra of quinolines , 2009 .

[24]  M. Schmitt,et al.  Ultrasensitive in situ tracing of the alkaloid dioncophylline A in the tropical liana Triphyophyllum peltatum by applying deep-UV resonance Raman microscopy. , 2007, Analytical chemistry.

[25]  Jürgen Popp,et al.  Raman spectroscopy--a prospective tool in the life sciences. , 2003, Chemphyschem : a European journal of chemical physics and physical chemistry.

[26]  A. Becke,et al.  Density-functional exchange-energy approximation with correct asymptotic behavior. , 1988, Physical review. A, General physics.

[27]  Jürgen Popp,et al.  Raman spectroscopy at the beginning of the twenty-first century , 2006 .

[28]  J. Greve,et al.  Studying single living cells and chromosomes by confocal Raman microspectroscopy , 1990, Nature.

[29]  M. Foley,et al.  Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents. , 1998, Pharmacology & therapeutics.

[30]  T. Wellems.  Plasmodium Chloroquine Resistance and the Search for a Replacement Antimalarial Drug , 2002, Science.

[31]  D. Sullivan,et al.  Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. , 1997, Annual review of microbiology.

[32]  Jürgen Popp,et al.  In vivo localization and identification of the antiplasmodial alkaloid dioncophylline A in the tropical liana Triphyophyllum peltatum by a combination of fluorescence, near infrared Fourier transform Raman microscopy, and density functional theory calculations. , 2006, Biopolymers.

[33]  D. Sullivan,et al.  On the molecular mechanism of chloroquine's antimalarial action. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  I. Robinson,et al.  Crystal nucleation, growth, and morphology of the synthetic malaria pigment beta-hematin and the effect thereon by quinoline additives: the malaria pigment as a target of various antimalarial drugs. , 2007, Journal of the American Chemical Society.

[35]  J. Perdew,et al.  Accurate and simple density functional for the electronic exchange energy: Generalized gradient approximation. , 1986, Physical review. B, Condensed matter.

[36]  M. Schmitt,et al.  In situ UV resonance Raman micro-spectroscopic localization of the antimalarial quinine in cinchona bark. , 2007, The journal of physical chemistry. B.

[37]  M. Peterson,et al.  Quinoline Binding Site on Malaria Pigment Crystal: A Rational Pathway for Antimalaria Drug Design , 2002 .

[38]  Don McNaughton,et al.  Resonance Raman spectroscopy reveals new insight into the electronic structure of beta-hematin and malaria pigment. , 2004, Journal of the American Chemical Society.

[39]  Peter W. Stephens,et al.  The structure of malaria pigment β-haematin , 2000, Nature.

[40]  Don McNaughton,et al.  Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites , 2003, FEBS letters.

[41]  M. Schmitt,et al.  Structural analysis of the anti-malaria active agent chloroquine under physiological conditions. , 2007, The journal of physical chemistry. B.

[42]  W. Trager,et al.  Human malaria parasites in continuous culture. , 1976, Science.