The Role of the Four Stereoisomers of the Heme Fe-O Cyclic Dimer in the Crystalline Phase Behavior of Synthetic Hemozoin: Relevance to Native Hemozoin Crystallization

TY - JOUR

T1 - The Role of the Four Stereoisomers of the Heme Fe-O Cyclic Dimer in the Crystalline Phase Behavior of Synthetic Hemozoin: Relevance to Native Hemozoin Crystallization

AU - Straasø, Tine

AU - Kapishnikov, Sergey

AU - Kato, Kenichi

AU - Takata, Masaki

AU - Als-Nielsen, Jens

AU - Leiserowitz, Leslie

PY - 2011/8/3

Y1 - 2011/8/3

N2 - Hemozoin is a crystalline byproduct formed upon host hemoglobin digestion in malaria-infected blood cells, crucial for parasitic survival. On the basis of published spectroscopic and X-ray powder diffraction (XRPD) data, hemozoin is believed to be very similar to the synthetic compound β-hematin, which consists of cyclic centrosymmetric dimers of ferriprotoporphyrin IX [Fe(3+) PPIX] molecules coordinated via Fe-O bonds. The enantio-facial symmetry of Fe(3+) PPIX implies, however, that four different Fe-O cyclic stereoisomers, two centrosymmetric and two chiral, of opposite handedness, should be formed in the crystallizing solution of β-hematin. A low-temperature XRPD study of β-hematin, i.e. synthetic hemozoin, revealed the presence, not only of the published phase (Pagola, S.; Stephens, P. W.; Bohle, D. S.; Kosar, A. D.; Madsen, S. K.Nature 2000, 404, 307) but also of a minor phase. We propose, based on Rietveld refinement and DFT+vdW computations (companion manuscript, DOI: 10.1021/cg200409d), that the minor phase consists mainly of the second centrosymmetric isomeric type in a crystal structure similar to that of the major phase. The enantiomeric chiral isomers may, on symmetry grounds, be enantioselectively occluded into the growing crystals, introducing disorder. The chiral dimers, on being first adsorbed on the crystal faces, would act as tailor-made additives, retarding crystal growth, which also explains the crystalline micrometer size. The existence of two phases in β-hematin may be crucial for a fuller understanding and more complete determination of the crystal structure of hemozoin, of which only one phase has crystallized according to published data.

AB - Hemozoin is a crystalline byproduct formed upon host hemoglobin digestion in malaria-infected blood cells, crucial for parasitic survival. On the basis of published spectroscopic and X-ray powder diffraction (XRPD) data, hemozoin is believed to be very similar to the synthetic compound β-hematin, which consists of cyclic centrosymmetric dimers of ferriprotoporphyrin IX [Fe(3+) PPIX] molecules coordinated via Fe-O bonds. The enantio-facial symmetry of Fe(3+) PPIX implies, however, that four different Fe-O cyclic stereoisomers, two centrosymmetric and two chiral, of opposite handedness, should be formed in the crystallizing solution of β-hematin. A low-temperature XRPD study of β-hematin, i.e. synthetic hemozoin, revealed the presence, not only of the published phase (Pagola, S.; Stephens, P. W.; Bohle, D. S.; Kosar, A. D.; Madsen, S. K.Nature 2000, 404, 307) but also of a minor phase. We propose, based on Rietveld refinement and DFT+vdW computations (companion manuscript, DOI: 10.1021/cg200409d), that the minor phase consists mainly of the second centrosymmetric isomeric type in a crystal structure similar to that of the major phase. The enantiomeric chiral isomers may, on symmetry grounds, be enantioselectively occluded into the growing crystals, introducing disorder. The chiral dimers, on being first adsorbed on the crystal faces, would act as tailor-made additives, retarding crystal growth, which also explains the crystalline micrometer size. The existence of two phases in β-hematin may be crucial for a fuller understanding and more complete determination of the crystal structure of hemozoin, of which only one phase has crystallized according to published data.

U2 - 10.1021/cg200410b

DO - 10.1021/cg200410b

M3 - Journal article

SN - 1528-7483

VL - 11

SP - 3342

EP - 3350

JO - Crystal Growth & Design

JF - Crystal Growth & Design

IS - 8

ER -