Egan T J, Hempelmann E, Mavuso W W
Department of Chemistry, University of Cape Town, Rondebosch, South Africa.
J Inorg Biochem. 1999 Jan-Feb;73(1-2):101-7. doi: 10.1016/S0162-0134(98)10095-8.
Infrared spectroscopy, elemental analysis and X-ray powder diffraction show that the product of 30 min of reaction of haematin in 4.5 M acetate, pH 4.5 at 60 degrees C is identical to beta-haematin prepared in 4.5 M acetic acid at 70 degrees C overnight (pH 2.6). There is no evidence for formation of haem-acetate complex, which could not be isolated, even from 11.4 M acetate solution. The antimalarial drugs quinidine, halofantrine, desbutylhalofantrine and mefloquine were found to inhibit formation of beta-haematin, while 5-, 6- and 8-aminoquinoline and quinoline were found to have no effect. Quinidine was shown to form a complex with ferriprotoporphyrin IX in 40% DMSO with log K = 5.02 +/- 0.03. Log K values for halofantrine and desbutylhalofantrine are 5.29 +/- 0.02 and 5.15 +/- 0.02 respectively (solutions containing 30% acetonitrile in addition to DMSO to solubilise these drugs), which are both stronger than chloroquine under the same conditions (log K = 4.56 +/- 0.02).
红外光谱、元素分析和X射线粉末衍射表明，在60℃下，血红素在pH值为4.5的4.5M乙酸盐中反应30分钟的产物与在70℃下于4.5M乙酸中过夜制备的β-血红素相同（pH值为2.6）。没有证据表明形成了血红素 - 乙酸盐络合物，即使从11.4M乙酸盐溶液中也无法分离出该络合物。发现抗疟药物奎尼丁、卤泛群、去丁基卤泛群和甲氟喹抑制β-血红素的形成，而5-、6-和8-氨基喹啉以及喹啉则没有影响。已证明奎尼丁在40%二甲基亚砜中与高铁原卟啉IX形成络合物，log K = 5.02±0.03。卤泛群和去丁基卤泛群的log K值分别为5.29±0.02和5.15±0.02（除二甲基亚砜外还含有30%乙腈的溶液以溶解这些药物），在相同条件下两者都比氯喹更强（log K = 4.56±0.02）。
