Characterisation of synthetic beta-haematin and effects of the antimalarial drugs quinidine, halofantrine, desbutylhalofantrine and mefloquine on its formation.
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).
Non‐iron porphyrins inhibit β‐haematin (malaria pigment) polymerisation
Infrared spectroscopy was used to evaluate the effect of non‐iron porphyrins (protoporphyrin IX and haematoporphyrin) on haematin polymerisation to β‐haematin at acidic pH. Both molecules effectively inhibited the reaction, with haematoporphyrin 6 times as active as protoporphyrin IX. We postulated that the interaction between the π electron system of porphyrin rings leads to the formation of π–π adducts, which inhibit polymer elongation in the same way as antimalarial drugs (e.g., chloroquine); the presence of hydroxyl groups able to bind haem iron enhances activity.
Ozonation of polycyclic aromatic hydrocarbons in oil/water-emulsions: mass transfer and reaction kinetics.
The ozonation of highly condensed polycyclic aromatic hydrocarbons (PAH) was studied in oil/water-emulsions, which are comparable to poorly water-soluble PAH in industrial wastewaters and at contaminated sites. As there was a lack of knowledge about the ozonation in oil/water-emulsions, first the ozone mass transfer was studied and optimized from the gas to the water phase and from the water to the oil phase. The ratio of mass transfer and oxidation reaction was determined by the Hatta-number and revealed a slow, quasi homogeneous reaction of ozone with PAH inside the oil droplets. Because the ozone gas concentration had no influence under the optimized conditions, the selective PAH-ozonation could be described microkinetically by a direct ozone reaction of pseudo-first order regarding PAH-concentrations. The determined PAH mean reaction rate constants of 1.02 min(-1) in oil/water-emulsions are in the upper range as found for PAH dissolved in water. These results give a new insight into the ozonation in the three-phase systems and into the treatment of highly condensed, hardly biodegradable PAH.