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).
Xanthones as antimalarial agents; studies of a possible mode of action
We recently demonstrated that 2,3,4,5,6‐pentahydroxyxanthone (X5) inhibits the in vitro growth of both chloroquine‐sensitive and multidrug‐resistant strains of P. falciparum. To study the molecular basis of its antimalarial action, we tested X5 and selected hydroxyxanthone analogs as inhibitors of in vitro heme polymerization in a low ionic strength phosphate solution at mildly acidic pH. We found that addition of 1 Eq. of X5 resulted in complete inhibition of polymerization in this system whereas addition of up to 40 Eqs. of standard antimalarial compounds (chloroquine, primaquine, quinacrine, artemisinin and methylene blue) had no such effect although these compounds did co‐precipitate with heme. The antimalarial potency of the hydroxyxanthones correlated well with their ability to inhibit in vitro heme polymerization in our assay, suggesting that these compounds exert their antimalarial action by preventing hemozoin formation. Based on the observed structure–activity relationships, we propose a model displaying possible interactions between hydroxyxanthones and heme.
“ PARTIALLY-ACTIVATED ” FLUX RESIDUE IMPACTS ON ELECTRONIC ASSEMBLY RELIABILITIES
The reliabilities of the flux residue of electronic assemblies and semiconductor packages are attracting more and more attention with the adoption of no-clean fluxes by majority of the industry. In recent years, the concern of “partiallyactivated” flux residue and their influence on reliability have been significantly raised due to the miniaturization along with high density design trend, selective soldering process adoption, and the expanded use of pallets in wave soldering process. When flux residue becomes trapped under low stand-off devices, pallets or unsoldered areas (e.g. selective process), it may contain unevaporated solvent, “live” activators and metal complex intermediates with different chemical composition and concentration levels depending on the thermal profiles. These partially-activated residues can directly impact the corrosion, surface insulation and electrochemical migration of the final assembly. In this study, a few application tests were developed internally to understand this issue. Two traditional liquid flux and two newly developed fluxes were selected to build up the basic models. The preliminary results also provide a scientific approach to design highly reliable products with the goal to minimize the reliability risk for the complex PCB designs and assembly processes.