No abstract

The presence of an ionized carboxyl group in the widely used non-steroidal anti-inflammatory (NSAID) drug diclofenac potassium results in a high mobility of diclofenac and in its low sorption under conditions of slow sand filtration or subsoil passage. No diclofenac degradation was detected in pure water or sludge during one month. Tertiary treatments of wastewater indicated that the effective removal of diclofenac was by reverse osmosis, but the removal by activated carbon was less satisfactory. This study presents an efficient method for the removal of diclofenac from water by micelle-clay composites that are positively charged, have a large surface area and include large hydrophobic domains. Adsorption of diclofenac in dispersion by charcoal and a composite micelle (otadecyltrimethylammonium [ODTMA] and clay [montmorillonite]) was investigated. Analysis by the Langmuir isotherm revealed that charcoal had a somewhat larger number of adsorption sites than the composite, but the latter had a significantly larger binding affinity for diclofenac. Filtration experiments on a solution containing 300 ppm diclofenac demonstrated poor removal by activated carbon, in contrast to very efficient removal by micelle-clay filters. In the latter case the weight of removed diclofenac exceeded half that of ODTMA in the filter. Filtration of diclofenac solutions at concentrations of 8 and 80 ppb yielded almost complete removal at flow rates of 30 and 60 mL min(-1). One kilogram of ODTMA in the micelle-clay filter has been estimated to remove more than 99% of diclofenac from a solution of 100 ppb during passage of more than 100 m3.

The binding of both wild-type and point-mutated E. coli single-stranded DNA-binding (SSB) protein to poly(deoxythymidylic acid) has been studied by fluorescence and optical detection of triplet state magnetic resonance spectroscopy. Involvement of tryptophan residues 40 and 54 in stacking interactions with nucleotide bases has been inferred earlier from such studies. Investigation of a point mutation in the E. coli SSB gene product obtained by site specific oligonucleotide mutagenesis in which Phe-60 is replaced by alanine strongly suggests the participation of Phe-60 in the binding process, possibly by the formation of an extended stacking structure by Trp-54, thymine and Phe-60. This hypothesis is supported by results on the point mutations in which His-55 is replaced by either leucine or tyrosine.

It is believed that the bitter taste of paracetamol, a pain killer drug, is due to its hydroxyl group. Hence, it is expected that blocking the hydroxy group with a suitable linker could inhibit the interaction of paracetamol with its bitter taste receptor/s and hence masking its bitterness. Using DFT theoretical calculations we calculated proton transfers in ten different Kirby's enzyme models, 1-10. The calculation results revealed that the reaction rate is linearly correlated with the distance between the two reactive centers (r(GM)) and the angle of the hydrogen bonding (α) formed along the reaction pathway. Based on these results three novel tasteless paracetamol prodrugs were designed and the thermodynamic and kinetic parameters for their proton transfers were calculated. Based on the experimental t(1/2) (the time needed for the conversion of 50% of the reactants to products) and EM (effective molarity) values for processes 1-10 we have calculated the t(1/2) values for the conversion of the three prodrugs to the parental drug, paracetamol. The calculated t(1/2) values for ProD 1-3 were found to be 21.3 hours, 4.7 hours and 8 minutes, respectively. Thus, the rate by which the paracetamol prodrug undergoes cleavage to release paracetamol can be determined according to the nature of the linker of the prodrug (Kirby's enzyme model 1-10). Further, blocking the phenolic hydroxyl group by a linker moiety is believed to hinder the paracetamol bitterness.

Fluorescence and optical detection of triplet state magnetic resonance spectroscopy have been employed to study the complexes formed by single-stranded polynucleotides with both E. coli single-stranded DNAbinding protein and an E. coli ssb gene product in which Tip-54 is replaced by phenylalanine using site specific oligonucleotide mutagenesis. Our results strongly suggest the involvement of Tip-54 in stabilizing the protein-nucleic acid complexes via stacking interactions of the aromatic residue with the nucleotide bases.ODMR spectroscopy; Single-stranded DNA binding protein; Stacking interaction; Zero field splitting; Heavy atom effect