Polymerisation of haematin to B-haematin (haemozoin or malaria pigment) in acidic acetate solutions was studied using infrared spectroscopy. The reaction was found to occur spontaneously between 6 and 65"C, in 0.1-4.5 M acetate and pH 4.2-5.0. The anti-malarial drugs quinine, chloroquine and amodiaquin were found to block spontaneous p-haematin formation, while the anti-malarially inactive 9-epiquinine and I-hydroxyquinoline had no effect on the reaction, as did primaquine, a drug which is active only against exo-erythrocytic stages of infection. It is argued that the intra-erythrocytically active anti-malarial agents act by binding to haematin, blocking j?-haematin formation and leaving toxic haematin in the parasite food vacuoles.

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conditions. Without additional data this small difference in the rate of decomposition does not allow us to conclude that the oxidized form further stabilizes the Cr(IV) species.O'Brien and Ozolins14 noted that at higher pH the dominant Cr(V) complexes decayed to Cr(III) products through a two-term rate law, a first-order process (first order in Cr(V); rate constant = 1.5 X 10"1 23 4s'1) and a second-order process (first order in each Cr(V) and GSH; rate constant = 9.1 X "3 M'1 s'1). At higher pH it is likely that the Cr(V) species undergoes parallel internal electron transfer and a direct reaction by a GSH molecule to form the Cr(IV) complex. This Cr(IV) complex is then rapidly reduced to Cr(III) products, in accord with our rate data showing that the second-order rate constant for the chromium(IV) decomposition (k = 0.13 M'1 s"1) in our system is at least 10 times larger than that for (k = 9.1 X 10"3 M'1 s'1) the decomposition of Cr(V) complexes.14 Acknowledgment. Funding of this research by the Kent State University Research Council is gratefully acknowledged. We thank Professors Wetterhahn and Gould for valuable discussions and Mr. Sutisak Kitareewan for helping with the recording of "time of fly" spectra during the HPLC separations. We are also grateful to reviewer no. 3 for incisive comments and helping with stylistic changes of the manuscript.

Spontaneous formation of beta-haematin (malaria pigment) from haematin in acetate solution follows pseudo-zero-order and not autocatalytic kinetics. Acetate appears to facilitate the reaction by solubilizing the haematin and acting as a phase-transfer catalyst, a role which, in vivo, could be fulfilled by carboxylic acids or amino acids.

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