Crystal Nucleation, Growth, and Morphology of the Synthetic
Malaria Pigment β-Hematin and the Effect Thereon by
Quinoline Additives: The Malaria Pigment as a Target of
Various Antimalarial Drugs
Inna Solomonov
Maria Osipova
Yishay Feldman
Carsten Baehtz
Kristian Kjaer
Ian K. Robinson
Grant T. Webster
Don McNaughton
Bayden R. Wood
Isabelle Weissbuch
Leslie Leiserowitz
10.1021/ja0674183.s001
https://acs.figshare.com/articles/journal_contribution/Crystal_Nucleation_Growth_and_Morphology_of_the_Synthetic_Malaria_Pigment_Hematin_and_the_Effect_Thereon_by_Quinoline_Additives_The_Malaria_Pigment_as_a_Target_of_Various_Antimalarial_Drugs/3020101
The morphology of micrometer-sized β-hematin crystals (synthetic malaria pigment) was
determined by TEM images and diffraction, and by grazing incidence synchrotron X-ray diffraction at the
air−water interface. The needle-like crystals are bounded by sharp {100} and {010} side faces, and capped
by {011} and, to a lesser extent, by {001} end faces, in agreement with hemozoin (malaria pigment) crystals.
The β-hematin crystals grown in the presence of 10% chloroquine or quinine took appreciably longer to
precipitate and tended to be symmetrically tapered toward both ends of the needle, due to stereoselective
additive binding to {001} or {011} ledges. Evidence, but marginal, is presented that additives reduce
crystal mosaic domain size along the needle axis, based on X-ray powder diffraction data. Coherent grazing
exit X-ray diffraction suggests that the mosaic domains are smaller and less structurally stable than in
pure crystals. IR-ATR and Raman spectra indicate molecular based differences due to a modification of
surface and bulk propionic acid groups, following additive binding and a molecular rearrangement in the
environment of the bulk sites poisoned by occluded quinoline. These results provided incentive to examine
computationally whether hemozoin may be a target of antimalarial drugs diethylamino-alkoxyxanthones
and artemisinin. A variation in activity of the former as a function of the alkoxy chain length is correlated
with computed binding energy to {001} and {011} faces of β-hematin. A model is proposed for artemisinin
activity involving hemozoin nucleation inhibition via artemisinin−β-hematin adducts bound to the principal
crystal faces. Regarding nucleation of hemozoin inside the digestive vacuole of the malaria parasite,
nucleation via the vacuole's membranous surface is proposed, based on a reported hemozoin alignment.
As a test, a dibehenoyl-phosphatidylcholine monolayer transferred onto OTS−Si wafer nucleated far more
β-hematin crystals, albeit randomly oriented, than a reference OTS−Si.
2007-03-07 00:00:00
hematin
hemozoin nucleation inhibition
malaria pigment
Various Antimalarial DrugsThe morphology
bulk propionic acid groups
TEM
alkoxy chain length
crystal mosaic domain size
stereoselective additive binding
OTS
diffraction