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Rhodes University for financial support and a bursary (E.O.O.) and the South African Medical Research Council (SAMRC) for support with funds from National Treasury under its Economic Competitiveness and Support Package.

A series of novel, substituted 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones have been prepared and shown to exhibit promising concentration-dependent activity against human SH-SY5Y cells, Plasmodium falciparum, Mycobacterium tuberculosis and P. aeruginosa. Substituent effects on observed bioactivity have been explored; the para-fluorophenyl derivative 3d exhibited activity across the range of the bioassays employed, indicating the potential of the 2-chloro-3-[(4-arylthiazol-2-yl)amino]-1,4-naphthoquinone scaffold in the development of novel, broad spectrum therapeutics.

Solvation of drugs in the core (C) and headgroup (H) strata of phospholipid bilayers affects their physiological transport rates and accumulation. These characteristics, especially a complete drug distribution profile across the bilayer strata, are tedious to obtain experimentally, to the point that even simplified preferred locations are only available for a few dozen compounds. Recently, we showed that the partition coefficient (P) values in the system of hydrated diacetyl phosphatidylcholine (DAcPC) and n-hexadecane (C16), as surrogates of the H- and C-strata of the bilayer composed of the most abundant mammalian phospholipid, PC, agree well with the preferred bilayer location of compounds. High P values are typical for lipophiles accumulating in the core, and low P values are characteristic of cephalophiles preferring the headgroups. This simple pattern does not hold for most compounds, which usually have more even distribution and may also accumulate at the H/C interface. To model complete distribution, the correlates of solvation energies are needed for each drug state in the bilayer: (1) for the H-stratum it is the DAcPC/W P value, calculated as the ratio of the C16/W and C16/DAcPC (W for water) P values; (2) for the C-stratum, the C16/W P value; (3) for the H/C interface, the P values for all plausible molecular poses are characterized using the fragment DAcPC/W and C16/W solvation parameters for the parts of the molecule embedded in the H- and C-strata, respectively. The correlates, each scaled by two Collander coefficients, were used in a nonlinear, mass-balance based model of intrabilayer distribution, which was applied to the easily measurable overall P values of compounds in the DMPC (M = myristoyl) bilayers and monolayers as the dependent variables. The calibrated model for 107 neutral compounds explains 94% of experimental variance, achieves similar cross-validation levels, and agrees well with the nontrivial, experimentally determined bilayer locations for 27 compounds. The resulting structure-based prediction system for intrabilayer distribution will facilitate more realistic modeling of passive transport and drug interactions with those integral membrane proteins, which have the binding sites located in the bilayer, such as some enzymes, influx and efflux transporters, and receptors. If only overall bilayer accumulation is of interest, the 1-octanol/W P values suffice to model the studied set.

The effect of two terpenes, carvone and limonene, on the biodegradation of DELOR 103, a commercial mixture of polychlorinated biphenyls (PCBs), by Pseudomonas stutzeri, an isolate from long-term PCB-contaminated soil, was studied in detail. The addition of both carvone and limonene as potential inducers of the dioxygenase metabolic pathway exerted an enhancing effect on PCB biodegradation when glycerol and xylose were used as carbon sources, whereas no such effect could be determined with biphenyl and glucose as substrates. Promising biodegradation values were determined with xylose as carbon source and carvone as terpene inducer. In this system, 30-70% of the congeners were degraded in the presence of 10 mg l(-1) and 20 mg l(-1) carvone, respectively, irrespective of the used concentration, whereas only 7-37% of individual PCB congeners were eliminated from the system without terpene addition.

This study evaluates the effects of Fenton's reagent (FR) on the rate and extent of the oxidative degradation of individual mono, di-, tri- and tetrachlorobiphenyls in the commercial mixture DELOR 103, equivalent to AROCLOR 1248. The oxidation effect of FR strongly increased with increasing the molar ratio of Fe 2+ /H 2 O 2 . The most effective oxidation of DELOR 103 (10 μg.ml −1 ) was achieved in a solution containing 1M H 2 O 2 and 1 mM Fe 2+ . The FR elimination rate constants of PCB congeners decrease with increasing number of chlorine substituents in the biphenyl molecule and show a good correlation with the values of molecular weights of the PCB congeners and their 1-octanol/water partition coefficients.

The mechanism of biphenyl biodegradation by Pseudomonas stutzeri was studied. Growth curves on biphenyl were measured, along with dissolution kinetics of biphenyl and production of biosurfactants by the bacterium. Biphenyl was supplied as pure crystals (the crystal biphenyl), adsorbed to Chromosorb G (the Chromosorb G biphenyl) or XAD-4 particles (the XAD-4 biphenyl). No lag phase was observed on the crystal biphenyl, while this period lasted 3.5-6.0 hours on the Chromosorb G biphenyl. The linear specific growth rates (LSGRs) ranged from 2.00 × 10(-4) to 293 × 10(-4) dry weight grams/L/h (d.w.g/L/h) on these two substrates. The LSGR values were directly proportional to the interfacial area between the solid substrate and the microbial suspension. The XAD-4 biphenyl was not bioavailable to the bacterium. The zero-order rates of dissolution ranged from 2.3 × 10(-5)to 8.0 × 10(-4) g/L/h on the crystal biphenyl and the Chromosorb G biphenyl. No biosurfactant production was observed on any biphenyl substrate. Growth curves, results of dissolution measurements and the scanning electron microscope (SEM) images indicate that Pseudomonas stutzeri takes up biphenyl from the aqueous phase as well as the solid phase of the crystal and the Chromosorb G biphenyl. The mechanism of uptake depends on the initial biphenyl concentration and the particle diameter of the biphenyl substrate.