PHOTOSENSITIZATION BY FENOFIBRATE. II. In vitro PHOTOTOXICITY OF THE MAJOR METABOLITES

Fenofibric acid, the major metabolite of fenofibrate, was found to be photolabile. Its irradiation in aqueous solution gave rise to two photoproducts, whose formation involves photodecarboxylation of the dissociated acid to an aryloxy-substituted carbanion, which is directly protonated or, alternatively, undergoes a Wittig rearrangement. A comparative in vitro phototoxicity study has been carried out on the anti-hyperlipoproteinemic drug fenofibrate, its metabolites and the photoproducts of fenofibric acid. Fenofibrate, fenofibric acid and its two photoproducts were found to be active when examined by the photohemolysis test and were able to photosensitize peroxidation of linoleic acid, as evidenced by the UV monitoring of dienic hydroperoxides. In summary, the major metabolite of fenofibrate (fenofibric acid), as well as its photoproducts, are phototoxic in vitro . This behavior can be attributed to the fact that the four compounds retain the benzophenone chromophore present in fenofibrate and is indicative of free radicalmediated photosensitization. In agreement with this rationalization, the metabolites with a reduced ketone functionality exhibit no detectable in vitro phototoxicity.     

Role of Hartree-Fock and Kohn-Sham orbitals in the basis set superposition error for systems linked by hydrogen bonds

In this work the effect of the basis set superposition error (BSSE) is explored with the counterpoise method on the occupied and unoccupied Hartree-Fock (HF) and Kohn-Sham (KS) orbitals. Three different systems linked by hydrogen bonds, H(2)O...FH, H(2)O...H(2)O, and H(2)O...CFH(3), were studied by using the basis set families cc-pVXZ and aug-cc-pVXZ (X = D, T, Q). The basis sets were tested with the HF method and two approximations for the exchange-correlation functional of KS: a generalized gradient approximation and a hybrid approach. In addition to these methods, the second-order M?ller-Plesset perturbation theory, MP2, was considered. It was found that the presence of the "ghost" basis set affects the orbitals in two ways: (1) The occupied KS orbitals are more sensitive to the presence of this "ghost" basis set than the occupied HF orbitals. For this reason the BSSE observed in HF is less than that obtained with KS. (2) The unoccupied HF orbitals are more sensitive to the presence of the "ghost" basis set than their corresponding occupied orbitals. Because the MP2 method uses both, occupied and unoccupied HF orbitals, to compute the total energy, the contribution of the BSSE is bigger than that obtained with HF or KS methodologies.     

Colloidal aggregation induced by long range attractions

The structure of colloidal clusters formed by long-range attractive interactions under diluted conditions is studied by means of Monte Carlo simulations. For a not-too-long attraction range, clusters show self-similar internal structure with lower density than that typical for diffusive aggregation. For long-range interactions, low kappa, nonfractal clusters are formed (dense at short scales but open at long ones). The dependence on the volume fraction shows that more-compact clusters are grown the higher the colloidal density for diffusive aggregation and attraction-driven aggregation in the fractal regime. The whole trend is explained in terms of the interpenetration among aggregates. In attraction-driven aggregations, the interpenetration of clusters competes with aggregation in the tips of the clusters, causing low-density clusters.     

The synthesis and reactivity of the heptanuclear dianion [Os7(CO)20]2− including the synthesis and structural characterizations of the compounds [Os7(CO)20(AuPEt)3 2] and [Os8(CO)20(η6-C6H6]

Reduction of the heptaosmium cluster [Os₇(CO)₂₁] With [Et₄N][NH₄) gives the cluster dianion [Os₇(CO)₂₀]^2–,1, in high yield. The reaction of the dianion with [AuPR ₃Cl] (R=Et or Ph) in the presence of TlPF₆ forms [Os₇((CO)₂₀(AuPR ₃)₂] [R=Et (2a);R = Ph(2b)] in 80% yield, while the corresponding reaction with (Os(C₆H₆)(CH₃CN)₃]²⁺ gives [Os₈(CO)₂₀ ( ⁶-C₆H₆)] (3) in reasonable yield (ca. 30%). The dianion,1, and the clusters2 and3 have been fully characterized by bout spectroscopic and crystallographic methods. The crystal structure of the [Ph₄P]⁺ salt of1 shows that the metals in the anion adopt a capped octahedral geometry, with all twenty carbonyl ligands in terminal sites. The metal core geometry in2a is best described as a tricapped octahedron, and is based on the structure of the dianion1 with two adjacent octahedral faces capped by the Au atoms of the two AuPEt₃ groups. In a similar fashion, the geometry of3 is related to that of1 with the addition of an Os(C₆H₆) unit capped to a triangular face, to give a bicapped octahedral framework.     

Deeply bound pionic states with the (Σ −,Λ) reaction

We study the reaction ^– +A + (A ^–) with the ^– bound in the nucleus, as a means of producing deeply bound pionic states in nuclei, so far unobserved. The reaction is similar to the (n, p) reaction but, because of the ^–, mass difference, it allows the reaction to occur with smaller momentum transfer, thus increasing the transition probability and reducing the effects of distortion. The ratios of signal to background are one to two orders of magnitude better than in the (n, p) reaction.We would like to thank C. Dover and G. Tamas who helped us to get a perspective of the present and future possibilities of this and other reactions.One of us, J. Nieves wishes to acknowledge a fellowship from the Ministerio de Educatión y Ciencia. This work is partially supported by the CICYT. All the calculations have been done in the Centro Informático de la Universidad de Valencia.     

Geometrization of the physics with teleparallelism. I. The classical interactions

A connection viewed from the perspective of integration has the Bianchi identities as constraints. It is shown that the removal of these constraints admits a natural solution on manifolds endowed with a metric and teleparallelism. In the process, the equations of structure and the Bianchi identities take standard forms of field equations and conservation laws.The Levi-Civita (part of the) connection ends up as the potential for the gravity sector, where the source is geometric and tensorial and contains an explicit gravitational contribution.Nonlinear field equations for the torsion result. In a low-energy approximation (linearity andlow energy-momentumtransfer), the postulate that only charge and velocities contribute to the source transforms these equations into the Maxwell system. Moreover, the affine geodesics become the equations of motion of special relativity with Lorentz force in the same approximation [J. G. Vargas,Found. Phys. 21, 379 (1991)]. The field equations for the torsion must then be viewed as applying to an electromagnetic/strong interaction.A classical unified theory thus arises where the underlying geometry confers their contrasting characters to Maxwell-Lorentz electrodynamics and to an Einstein's-like theory of gravity. The highly compact field equations must, however, be developed in phase-spacetime, since the connection is velocity-dependent, i.e., Finsler-like.Further opportunities for similarities with present-day physics are discussed: (a) teleparallelism allows for the formulation of the torsion sector of the theory as a flat space theory with concomitant point-dependent transformations; (b) spinors should replace Lorentz frames in their role as the subjects to which the connection refers; (c) the Dirac equation consistent with the frame bundle for a velocity-dependent metric with Lorentz signature generates a weak-like interaction in the torsion sector.Work done at the Department of Mathematics and Physics of the Interamerican University of Puerto Rico, San German, Puerto Rico 00683.     

Effect of electrolyte type on the electrokinetic behavior of sulfonated polystyrene model colloids

Sulfonated polystyrene latex particles were prepared by a two-stage shot-growth emulsion polymerization process in the absence of emulsifier. Sodium styrene sulfonate (NaSS) was used as an ionic co-monomer to produce a series of latex particles with the same particle size but with different surface charge densities. The electrophoretic mobility of this functionalized model colloid was studied in the presence of various types of inorganic electrolytes. The _e curves of these latexes exhibit a pronounced maximum at high electrolyte concentrations: 5·10^–2 M for 11 electrolytes and 10^–2 M for 21 and 12 electrolytes. When a 31 electrolyte (LaCl₃) was used, the electrophoretic mobility changed to positive values at high concentration due to the specific adsorption of lanthanum species. The experimental results for the electrokinetic characterization of these sulfonated polystyrene model colloids suggest that the surface of the particles is covered by a layer of oligomers or polymer chains which shift the shear plane toward the bulk solution, increasing the anomalous surface conductance of the polystyrene microsphere-electrolyte solution interface.     

Trace determination of lead by helium-4 activation analysis

The determination of lead via 30 MeV⁴He bombardment to produce the long-lived radioisotope²¹⁰Po was studied. The validity of the technique was tested by the analysis of a series of NBS glass samples doped with 61 different trace elements at nominal 500 to 1 ppm level concentrations. The measurement sensitivity of alpha counting with surface barrier detectors was evaluated. The detection limit was estimated at 0.1 ppm. The⁴He-activation technique coupled with -counting features a unique combination of sensitivity and accuracy for the trace determination of lead.