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We first focus on the <jats:italic>in\u2010vivo<\/jats:italic> formation of hemozoin. A model is presented, based on native\u2010contrast 3D imaging obtained by X\u2010ray and electron microscopy, that hemozoin nucleates at the inner membrane leaflet of the parasitic digestive vacuole, and grows in the adjacent aqueous medium. Having observed quantities of hemoglobin and hemozoin in the digestive vacuole, we present a model that heme liberation from hemoglobin and hemozoin formation is an assembly\u2010line process. The crystallization is preceded by reaction between heme monomers yielding hematin dimers involving fewer types of isomers than in synthetic hemozoin; this is indicative of protein\u2010induced dimerization. Models of antimalarial drugs binding onto hemozoin surfaces are reviewed. This is followed by a description of bromoquine, a chloroquine drug analogue, capping a significant fraction of hemozoin surfaces within the digestive vacuole and accumulation of the drug, presumably a bromoquine\u2013hematin complex, at the vacuole's membrane.<\/jats:p>","DOI":"10.1002\/cmdc.202000895","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T20:31:40Z","timestamp":1612297900000},"page":"1515-1532","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Malaria Pigment Crystals: The Achilles\u2032 Heel of the Malaria Parasite"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-054X","authenticated-orcid":false,"given":"Sergey","family":"Kapishnikov","sequence":"first","affiliation":[{"name":"Dept. of Chemical Research Support Weizmann Institute of Science  Rehovot 7610001 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"Hempelmann","sequence":"additional","affiliation":[{"name":"Center of Cellular and Molecular Biology of Diseases Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP)  City of Knowledge 0843 (Republic of Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Elbaum","sequence":"additional","affiliation":[{"name":"Dept. of Chemical and Biological Physics Weizmann Institute of Science  Rehovot 7610001 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Als\u2010Nielsen","sequence":"additional","affiliation":[{"name":"Niels Bohr Institute University of Copenhagen  2100 Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Leiserowitz","sequence":"additional","affiliation":[{"name":"Dept. of Molecular Chemistry and Materials Science Weizmann Institute of Science  Rehovot 7610001 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"e_1_2_11_1_1","unstructured":"A.\u2005C. 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