Revising the Formation of -Hematin Crystals from Hemin in Aqueous-Acetate Medium Containing Chloroquine: Modeling the Kinetics of Crystallization and Characterizing Their Physicochemical Properties

We investigated the kinetics of conversion of hemin to beta-hematinin aqueous-acetate medium in the absence and in the presence of twoconcentrations of chloroquine by using 11 reported kinetic equations.The two best kinetic equations are the combination of order 1 andAvrami and the combination of second order and logistic equations,based on the statistical parameter variance and overall errors. Thebest fitted equations are composed of two terms from which we modelthe formation of beta-hematin as the result of two processes: theavailability of reactive precursors and the formation of nucleationand growth sites. The crystals exhibit needle-like morphologies about760-nm-long and 140-nm-wide. However, the increment of chloroquinefavors the formation of crystal twinning with nonhomogenous distribution,crystals with lower sizes of similar heights and widths, and crystalssymmetrically tapered at the ends of the needles. The lattice volumes,obtained from Rietveld analysis of powder X-ray diffraction patterns,were not regularly affected by chloroquine. The main IR absorptionbands did not appreciably change in positions nor in intensities withvarying chloroquine concentration. However, important changes wereobserved in the 2000-4000 cm(-1) region. Weused density functional theory calculations to understand these changes. Our manuscript investigates the mechanismsof beta-hematincrystallization and chloroquine inhibition by using kinetic studiesand physicochemical quantitative characterization and simulation.