Publications

Abstract The analysis of opiates is of vital interest in drug abuse monitoring and research. This review presents a general overview of the electrochemical methods used for detection and quantification of opiates in a variety of matrices. Emphasis has been placed on the voltammetric methods used for study and determination of morphine, codeine, and heroin. Specific issues that need to be solved and better explained as well as future trends in the use of electrochemical methods in the examination of opiates are also discussed.

Abstract A complete conformational analysis of beta-nitrostyrene and beta-methyl-beta-nitrostyrene derivatives was carried out by Raman spectroscopy coupled to ab initio MO calculations. Apart from the optimised geometrical parameters of the most stable conformers of the molecules under study, the corresponding harmonic vibrational frequencies were calculated, as well as potential-energy profiles for several internal rotations within the molecules. At the light of these results, a complete assignment of the Raman spectra of the solid samples was performed. The conformational behaviour of this kind of systems was found to be mainly determined by the stabilising effect of pi-electron delocalisation.

Abstract A conformational analysis of 3-(3,4,5-trihydroxyphenyl)-2-propenoic acid (3,4,5-trihydroxycinnamic acid, THPPE), a trihydroxylated cinnamic acid analogous to caffeic acid (a natural compound often present in diet), was carried out by Raman spectroscopy coupled to Ab initio MO calculations. Apart from the optimised geometrical parameters for the most stable conformers of this compound, and for one of its dimeric species, the corresponding harmonic vibrational frequencies, as well as potential-energy profiles for rotation around several bonds within the molecule, were obtained. Twenty one distinct conformers were found for THPPE, the lowest energy ones-THPPE 1 and THPPE 2-displaying a completely planar geometry. The conformational preferences of this system were thus found to be mainly ruled by the stabilising effect of pi-electron delocalisation. At the light of these results, a complete assignment of the corresponding solid state Raman spectra was performed.

Abstract The oxidative behavior of heroin in aqueous solution is reported. In order to identify its oxidation peaks, several metabolites, 6-monoacetylmorphine, 3-monoacetylmorphine and norheroin, were synthesized and their electrochemical behavior studied using differential pulse voltammetry. The anodic waves observed for heroin correspond to the oxidation of the tertiary amine group and its follow-up product (secondary amine), and to the oxidation of the phenolic group obtained from hydrolysis, at alkaline pHs, of the 3-acetyl group. The results enabled a new oxidative mechanism for heroin to be proposed in which a secondary amine, norheroin, and an aldehyde are obtained. The voltammetric behavior of 6-monoacetylmorphine and morphine was found to be similar demonstrating that the presence of an acetyl substituent on the 6-hydroxy group does not have a relevant influence on the peak potential of the wave resulting from oxidation of the 3-phenolic group.

Abstract The oxidation of codeine on glassy carbon electrodes has been studied in detail using differential pulse voltammetry. The results obtained using a glassy carbon electrode clearly show a much more complex oxidation mechanism than that previously reported when platinum and gold electrodes were used. To clarify the codeine oxidative profile, several metabolites and analogues of this alkaloid, codeine N-oxide, norcodeme, dihydrocodeine, acetylcodeine and 6-chlorodesoxycodeine, were synthesized and studied. It was deduced that the anodic waves observed in codeine oxidation are related to the presence of methoxy, hydroxy and tertiary amine groups. Due to the similarity of potentials at which these oxidative processes take place, at some pHs an overlap of peaks occurs and only one anodic wave is observed.

Abstract A detailed study of the electrochemical oxidative behavior of morphine in aqueous solution is reported. Through the synthesis of several metabolites and derivatives, pseudomorphine, morphine N-oxide, normorphine, dihydromorphine and 2-(N,N-dimethylaminomethyl)morphine, and their voltammetric study it was possible to identify the oxidation peaks for morphine. The anodic waves are related with the oxidation of phenolic and tertiary amine groups. It is also possible to verify that a poorly defined peak observable during morphine oxidation is not a consequence of further oxidation of pseudomorphine but due to formation of a dimer during phenolic group oxidation. The results obtained and especially those regarding the formation of a new polymer based on a C-O coupling could be useful for clarifying the discoloration phenomenon occurring during storage of morphine solutions as well as leading to a better understanding of its oxidative metabolic pathways.

Abstract In the past decade, clinical evidence has increasingly shown that the liver is a target organ for 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") toxicity. The aims of the present in vitro study were: (1) to evaluate and compare the hepatotoxic effects of MDMA and one of its main metabolites, N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and (2) to investigate the ability of antioxidants, namely ascorbic acid and N-acetyl-L-cysteine (NAC), to prevent N-Me-alpha-MeDA-induced toxic injury, using freshly isolated rat hepatocytes. Cell suspensions were incubated with MDMA or N-Me-alpha-MeDA in the final concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 mM for 3 It. To evaluate the potential protective effects of antioxidants, cells were preincubated with ascorbic acid in the final concentrations of 0.1 and 0.5 mM, or NAC in the final concentrations of 0.1 and I mM for 15 min before treatment with 1.6 mM N-Me-alpha-MeDA for 3 In (throughout this incubation period the cells were exposed to both compounds). The toxic effects were evaluated by measuring the cell viability, glutathione (GSH) and glutathione disulfide (GSSG), ATP and the cellular activities of GSH peroxidase (GPX), GSSG reductase (GR), and GSH S-transferase (GST). MDMA induced a concentration- and time-dependent GSH depletion, but had a negligible effect on cell viability, ATP levels, or on the activities of GR, GPX, and GST. In contrast, N-Me-alpha-MeDA was shown to induce not only a concentration- and time-dependent depletion of GSH, but also a depletion of ATP levels accompanied by a loss in cell viability, and decreases in the antioxidant enzyme activities. For both compounds, GSH depletion was not accompanied by increases in GSSG levels, which seems to indicate GSH depletion by adduct formation. Importantly, the presence of ascorbic acid (0.5 mM) or NAC (1 mM) prevented cell death and GSH depletion induced by N-Me-alpha-MeDA. The results provide evidence that MDMA and its metabolite N-Me-alpha-MeDA induce toxicity to freshly isolated rat hepatocytes. Oxidative stress may play a major role in N-Me-alpha-MeDA-induced hepatic toxicity since antioxidant defense systems are impaired and administration of antioxidants prevented N-Me-alpha-MeDA toxicity.

Abstract In nonequimolar solutions of a cationic and an anionic surfactant, vesicles bearing a net charge can be spontaneously formed and apparently exist as thermodynamically stable aggregates. These vesicles can associate strongly with polymers in solution by means of hydrophobic and/or electrostatic interactions. In the current work, we have investigated the rheological and microstructural properties of mixtures of cationic polyelectrolytes and net anionic sodium dodecyl sulfate/didodecyldimethylammonium bromide vesicles. The polyelectrolytes consist of two cationic cellulose derivatives with different charge densities; the lowest charge density polymer contains also hydrophobic grafts, with the number of charges equal to the number of grafts. For both systems, polymer-vesicle association leads to a major increase in viscosity and to gel-like behavior, but the viscosity effects are more pronounced for the less charged, hydrophobically modified polymer. Evaluation of the frequency dependence of the storage and loss moduli for the two systems shows further differences in behavior: while the more long-lived cross-links occur for the more highly charged hydrophilic polymer, the number of cross-links is higher for the hydrophobically modified polymer. Microstructure studies by cryogenic transmission electron microscopy indicate that the two polymers affect the vesicle stability in different ways. With the hydrophobically modified polymer, the aggregates remain largely in the form of globular vesicles and faceted vesicles (polygon-shaped vesicles with largely planar regions). For the hydrophilic polycation, on the other hand, the surfactant aggregate structure is more extensively modified: first, the vesicles change from a globular to a faceted shape; second, there is opening of the bilayers leading to holey vesicles and ultimately to considerable vesicle disruption leading to planar bilayer, disklike aggregates. The faceted shape is tentatively attributed to a crystallization of the surfactant film in the vesicles. It is inferred that a hydrophobically modified polyion with relatively low charge density can better stabilize vesicles due to formation of molecularly mixed aggregates, while a hydrophilic polyion with relatively high charge density associates so strongly to the surfactant films, due to strong electrostatic interactions, that the vesicles are more perturbed and even disrupted.

Abstract The Knudsen mass-loss effusion technique was used to measure the vapour pressures at different temperatures of the following 4-n-alkylbenzoic acids: 4-methylbenzoic acid, between 319.68 K and 337.33 K, 4-ethylbenzoic acid, between 321.17 K and 335.25 K, 4-propylbenzoic acid, between 331.16 K and 347.16 K, 4-butylbenzoic acid, between 333.16 K and 349.15 K, 4-pentylbenzoic acid, between 341.16 K and 357.16 K, 4-hexylbenzoic acid, between 347.08 K and 363.14 K, 4-heptylbenzoic acid, between 353.16 K and 369.20 K and 4-octylbenzoic acid, between 356.67 K and 371.86 K. From the temperature dependence of the vapour pressure of the crystalline compounds, the standard, pdegrees = 10(5) pa, molar enthalpies, entropies and Gibbs energies of sublimation at T = 298.15 K, were derived. A d.s.c. study of the crystalline polymorphic transitions, fusion and isotropization of liquid crystals is also presented.

Abstract The standard molar enthalpies of combustion and sublimation of 2- and 4-biphenylcarboxylic acid, 2,2'- and 4,4'-biphenyldicarboxylic acid were measured and the gas-phase enthalpies of formation, at T = 298.15 K, were determined. Ab initio calculations were performed and a theoretical study on molecular structure of all the biphenyl acid isomers has been carried out. Calculated enthalpies of formation using appropriate isodesmic reactions are compared with experimental values, and a good agreement is observed. Estimates of enthalpies of formation for the isomers, which were not studied experimentally, are presented. All the acids containing at least one ortho COOH are comparatively less stable than their isomers having just meta or para COOH group(s).