GEOMETRY OF INTERCALATION OF PSORALENS IN DNA APPROACHED BY MOLECULAR MECHANICS*

The results of molecular mechanical calculations on intercalation complexes of 3-carbethoxypsoralen, 5-methoxypsoralen, 8-methoxypsoralen, 7-methylpyrido[3,4-c]psoralen (MepyPs) and 7-methylpyrido[4,3-c]psoralen (2N-MePyPs) with the double stranded duodecanucleotide d(CGCGATATCGCG)2 are presented. In the energy-minimized structures, the psoralens are intercalated with their plane orthogonal to the helix axis. Stacking interactions between the furan ring of the psoralen and the adjacent bases are maximized in most derivatives studied, whereas the effect of the various substituents of the psoralen ring is to specifically push part of the molecule towards either the minor or the major groove, preventing a symmetrical intercalation (with respect to the two strands of the DNA). The relative position of the psoralen ring and of the adjacent thymine foreshadows the formation of furan-side monoadducts in 3-CPs, MePyPs and 2N-MePyPs, whereas the formation of a pyrone-side monoadduct appears as geometrically more favourable in 5-MOP and both furan- and pyrone-side monoadducts can be geometrically envisaged in 8-MOP. A good correlation therefore exists between the more or less favourable equilibrium geometries and the experimentally observed photoreactions. The present study is the first attempt to characterize the geometrical parameters as part of a complex set of geometrical, dynamical and excited state parameters governing the overall DNA-psoralen photoreaction.     

Catalytic partial oxidation of hydrogen sulfide on chabazite tuff

The catalytic activity of a chabazite tuff in the partial oxidation of H₂S to sulfur has been determined. The effects of temperature, feed concentration and chemical composition of the tuff on H₂S conversion and selectivity to sulfur have been investigated. Encouraging results in view of a possible use in H₂S removal processes have been obtained.

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Thermally induced sign change of Soret coefficient for dilute and semidilute solutions of poly(N-isopropylacrylamide) in ethanol

We studied the thermal diffusion behavior of poly(N-isopropylacrylamide) (PNiPAM) in ethanol in a temperature range from T = 14.0 degrees C to T = 40.0 degrees C by means of thermal diffusion forced Rayleigh scattering. The obtained Soret coefficient S(T) of PNiPAM was positive for lower temperatures (T < 34 degrees C), while S(T) showed a negative value for higher temperatures (T > 34 degrees C). This means PNiPAM molecules move to the cold side for temperatures T < 34 degrees C, whereas they move to the warm side for T > 34 degrees C. This is the first nonaqueous polymeric system for which a sign change with temperature has been observed. We performed static and dynamic light scattering experiments in the same temperature range. The second virial coefficient determined from dilute solutions by static light scattering (SLS) was positive in the comparable temperature range. The results of SLS for the semidilute solution showed a strong repulsion among PNiPAM chains which was enhanced by increasing temperature. These results imply that the observed thermally induced sign change of S(T) does not depend on the intermolecular interactions among PNiPAM chains.     

Copper-assisted oxidation of catechols into quinone derivatives

Catechols are ubiquitous substances often acting as antioxidants, thus of importance in a variety of biological processes. The Fenton and Haber–Weiss processes are thought to transform these molecules into aggressive reactive oxygen species (ROS), a source of oxidative stress and possibly inducing degenerative diseases. Here, using model conditions (ultrahigh vacuum and single crystals), we unveil another process capable of converting catechols into ROSs, namely an intramolecular redox reaction catalysed by a Cu surface. We focus on a tri-catechol, the hexahydroxytriphenylene molecule, and show that this antioxidant is thereby transformed into a semiquinone, as an intermediate product, and then into an even stronger oxidant, a quinone, as final product. We argue that the transformations occur via two intramolecular redox reactions: since the Cu surface cannot oxidise the molecules, the starting catechol and the semiquinone forms each are, at the same time, self-oxidised and self-reduced. Thanks to these reactions, the quinone and semiquinone are able to interact with the substrate by readily accepting electrons donated by the substrate. Our combined experimental surface science and ab initio analysis highlights the key role played by metal nanoparticles in the development of degenerative diseases.

An antioxidant catechol transforms following intramolecular redox reactions into highly reactive oxygen species, a semiquinone and a quinone, on copper.     

Validation of UV spectrophotometric and nonaqueous titration methods for the determination of carvedilol in pharmaceutical formulations

Ultraviolet (UV) spectrophotometric and nonaqueous volumetric methods are described for the determination of carvedilol in pharmaceutical formulations. Linearity, precision, and accuracy were evaluated according to the validation guidelines of the International Conference on Harmonization and the United States Pharmacopeia for both methods. The UV spectrophotometric procedure was performed in ethanol at 244 nm. Good linearity was obtained between 2 and 7 microg/mL with a correlation coefficient of 0.9999. The intra- and interday precision values were <2% for all samples analyzed. The accuracy, determined from recovery studies, was between 97.5 and 102.2%. The other procedure was based on the volumetric quantitation of carvedilol in a nonaqueous medium with 0.01 M perchloric acid and 1% violet crystal as the indicator. The validation of the volumetric method yielded good results that included linearity (r of > 0.999), precision (relative standard deviations of <2% for intra- and interday precision), and accuracy (96.4-102.4%). The methods were applied to tablets and compounded capsules. Statistical analysis by analysis of variance showed no significant difference between the results obtained by the proposed methods.