Sandra Jurić

Effect of the Leaving Group and Solvent Combination on the LFER Reaction Constants

Fine effects that influence the variations of the reaction constants sf in LFER log k = sf(Nf + Ef) have been summarized here. Increasing solvent polarity in the series of binary mixtures increases the solvolysis rates for the same factor for all benzhydryl derivatives in which the solvation of the leaving group moiety in the transition state is substantial, i.e., log k vs. Ef correlation lines are parallel (same sf). For the substrates in which the demand for solvation of the leaving groups moiety is reduced, (e.g., carbonates) sf parameters decrease as the fraction of the water in a given solvent/water mixture increases (log k vs. Ef plots converge), due to decreasing solvation of the electrofuge moiety toward bigger electrofugality. The abscissa of the intersection of the converging plots might indicate the critical electrofugality above which the solvolysis rates should not depend of the water fraction. Larger reaction constant sf indicate later transition state for structurally related substrates only, while sf parameters for structurally different substrates cannot be compared likely due to different intrinsic barriers. Inversion in relative abilities of leaving groups is possible if they have similar reactivities and are characterized with different reaction constants.

Bismuth nanoparticles-carbon nanotubes modified sensor for sulfasalazine analysis

Nanocomposite of bismuth nanoparticles and carbon nanotubes in Nafion matrix was used as modifier for glassy carbon electrode in analysis of anti-inflamatory drug sulfasalazine. The nanocomposite surface exhibited exceptional synergy and remarkable enhancement effect to the voltammetric response of drug. The surface morphology and structure characterization of the modified electrodes was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy and cyclic voltammetry. The sensor exhibited excellent electroanalytical performance for drug determination in comparison with bismuth film electrode. The adsorptive stripping square-wave voltammetric signal showed a good linear correlation to sulfasalazine concentration in a broad range from 5.0×10-8 to 1.0×10-5M with low detection limit of 1.3×10-8M.The method was successfully utilised for drug quantification in human serum samples and good recoveries were obtained without interference from endogenous substances, 5-aminosalycilic acid and sulfapyridine formed after biotransformation of drug and folic acid co-administered as the supplement during sulfasalazine therapy. Additionally, the proposed sensor was successfully applied to analysis of sulfasalazine content in gastro-resistant pharmaceutical dosage forms.

Leaving group property of dimethyl sulfide.

The LFER equation log k = s(f)(E(f) + N(f)) was used to derive the nucleofuge specific parameters (N(f) and s(f)) for dimethyl sulfide in the series of aqueous alcohols, using the S(N)1 solvolysis rate constants obtained for X-substituted benzhydryl dimethyl sulfonates 1-5. The slope parameters (s(f)) are practically independent of the solvent used, while N(f) parameters slightly decrease as the polarity of the solvent increases.

Electrochemical sensing of mesalazine and its N-acetylated metabolite in biological samples using functionalized carbon nanotubes.

A rapid analytical method without the time-consuming separation step was developed to simultaneously determine mesalazine and its N-acetylated metabolite. A simply designed electrochemical sensor with functionalized carbon nanotubes in a Nafion matrix was constructed for this purpose. The presence of the nanocomposite modifier on the electrode surface significantly affects the voltammetric response of target analytes. The morphology of the modified surface was investigated by scanning electron microscopy. The effect of modifier amount on the sensor performance was investigated in order to obtain the most favorable response of mesalazine since it was found in lower concentration limits in real samples then its metabolite due to the rapid drug elimination and the slightly slower renal metabolite excretion. Under optimal conditions, the anodic peak currents measured by square-wave voltammetry increased linearly after short accumulation of 30s in the range of 5.0×10(-8)-2.5×10(-6)M and 1.0×10(-7)-5.0×10(-6)M for drug and metabolite, respectively. In addition to stable response, the sensor has excellent performance associated with high sensitivity (2.33×10(7) and 8.37×10(6)µAM(-1) for drug and metabolite, respectively). The synergistic effect of the carbon nanotubes and Nafion polymer film yielded detection limit of 1.2×10(-8)M for mesalazine and 2.6×10(-8)M for its metabolite that is comparable to known chromatographic methods. Due to the easy preparation and regeneration, the proposed sensor opens new opportunity for fast, simple and sensitive analysis of drug and its metabolite in human serum samples as well as direct quantification of mesalazine in delayed-release formulations.