Photochemically generated stable cation radical of phenothiazine aggregates in mildly acid buffered solutions

This work characterizes, for the first time, the photochemical behavior of the antipsychotic drugs thioridazine (TR), trifluoperazine (TFP), and fluphenazine (FP) influenced by the aggregation state of the molecules. Samples of monomeric and aggregated forms of phenothiazines were submitted to 20 min of irradiation at 254 nm for intervals of 1, 5, 10, 15, 20, or 25 days. In high phenothiazine concentrations, the irradiation led to the appearance of absorbance bands in the visible region peaking at 633 nm for TR and 509 nm for FP and TFP. In the dark, at room temperature and at 4 degrees C, these bands disappeared, after approximately 15 and approximately 60 min, respectively, but reappeared after a new irradiation session. These visible bands were assigned to stable cation radicals that were characterized by direct EPR measurements and by flash photolysis. Photogenerated stable cation radicals in the phenothiazine aggregates at room temperature are formed probably due to the stacking of the thiazine phenyl moieties. For the monomeric forms of phenothiazines, the spectral changes observed during the irradiation suggested the formation of sulfoxide and hydroxylated derivates. Oxidized derivates were detected by mass spectrometry of the aggregated forms of phenothiazines (>100 microM) only in the samples irradiated for more than 20 days. In contrast, monomeric phenothiazines were totally converted to the oxidized forms after 20 min of irradiation. Surface tension measurements of phenothiazines revealed that, in concentrations above 100 microM, the drugs formed aggregates. In the case of TR, small-angle X-ray scattering measurements indicated that this compound forms large lamellar-like aggregates in aqueous solutions.     

Electroanalytical determination of eugenol in clove oil by voltammetry of immobilized microdroplets

Journal of Solid State Electrochemistry - The determination of eugenol employing voltammetry of immobilized microdroplets (VIM) is reported in this work. The construction of the electrode was based...     

Antisymmetric exchange in [2Fe-2S]1+ clusters: EPR of the Rieske protein from Thermus thermophilus at pH 14

[2Fe-2S] clusters found in the xanthine oxidase family of proteins exhibit an S = 1/2 EPR feature, called signal II, for which one g-value is significantly above g = 2.0. The g-values of signal II cannot be explained with the standard spin coupling model that has been so successful in describing the g = 1.94 signals of [2Fe-2S] ferredoxins. We have studied the EPR spectra of the Rieske protein from Thermus thermophilus at pH 14 and observed a signal II-type EPR spectrum, with g-values at 1.81, 1.94, and 2.14. It is shown that the g-values of signal II can be explained by including an antisymmetric exchange term, d.S1xS2, in the spin Hamiltonian. The presence of this term is sensed by EPR if the isotropic exchange coupling constant J is sufficiently small. For the Rieske protein we determined J = 43 cm-1 which is at least 4 times smaller than the J values reported for [2Fe-2S] clusters that yield standard g = 1.94 signals.     

Unexpected transformation of quinones to spirolactones and to naturally occurring naphthalenic compounds

In the last few years, natural quinones of the lapachol group have been used as starting points for the preparation of several bioactive heterocyclic compounds. Herein, we announce that lapachones, derivatives of lapachol, under certain conditions in the presence of inorganic reagents give unexpected products, spirolactones and naphthalenic derivatives, nordihydrolapachenone and tetrahydrotectol, both naturally occurring compounds. Nordihydrolapachenone was identified by X-ray analysis. Lapachol itself can also be converted to tetrahydrotectol.     

Photoisomerization of azobenzene from first-principles constrained density-functional calculations

Despite considerable work in the field, the precise mechanism for the photoisomerization of azobenzene, C(12)H(10)N(2), is still an open issue. Early theoretical studies of the problem indicated that isomerization occurs through an in-plane inversion path, and this has been used to explain recent time-resolved UV-visible spectroscopy measurements. On the other hand, a number of recent theoretical studies have concluded that a torsion of the N-N bond ("rotation path") is probably the most favorable mechanism for photoisomerization involving the first excited state. We have performed first-principles calculations using constrained density-functional theory (DFT) and time-dependent DFT in the local-density approximation, with results that also favor the rotation path mechanism. Our results are compared with other analyses, primarily based on configuration interaction.     

Mechanisms of nucleophilic substitution reactions of methylated hydroxylamines with bis(2,4-dinitrophenyl)phosphate. Mass spectrometric identification of key intermediates

Mono- and dimethylation of hydroxylamine on nitrogen does not significantly affect rates of initial attack of NHMeOH and NMe(2)OH on bis(2,4-dinitrophenyl)phosphate (BDNPP), which is largely by oxygen phosphorylation. O-Methylation, however, blocks this reaction and NH(2)OMe then slowly reacts with BDNPP via N-attack at phosphorus and at the aryl group. With NHMeOH, the initial product of O-attack at phosphorus reacts further, either by reaction with a second NHMeOH or by a spontaneous shift of NHMe to the aryl group via a transient cyclic intermediate. There is a minor N-attack of NHMeOH on BDNPP in an S(N)2(Ar) reaction. Reactions occurring via N-attack are blocked by N-dimethylation, and reaction of NMe(2)OH with BDNPP occurs via O-attack, generating a long-lived product. Reaction mechanisms have been probed, and intermediates identified, by using both NMR and MS spectroscopy, with the novel interception of key reaction intermediates in the course of reaction by electrospray ionization mass and tandem mass spectrometry.     

Quenching of Myosin Intrinsic Fluorescence Unravels the Existence of a High Affinity Binding Site for Decavanadate

Decavanadate, one of the aggregated species of vanadate, is a potent inhibitor of several enzymes, including skeletal muscle myosin. However, its putative binding sites in myosin are largely unknown. Titration of the intrinsic fluorescence of myosin, purified from rabbit skeletal muscle, have been carried out in 0.3 M KCl, 5 mM CaCl₂ and 25 mM Tris-HCl (pH 7.0), with 0.1 mg/ml myosin. In the 0-200 M total vanadate concentration range, decavanadate produced approximately 25% quenching of the intrinsic fluorescence of myosin, with an apparent dissociation constant in the micromolar range. This effect was found to be specific of decavanadate, because titration with metavanadate up to 200 M did not produce a significant quenching of the intrinsic fluorescence of myosin. This quenching was accompanied by a parallel decrease of the accessibility of myosin tryptophans to the water-soluble collisional quencher KI, with an apparent dissociation constant also in the micromolar range. It is concluded that the binding of decavanadate to high-affinity sites in myosin produces local conformational change(s) near the tryptophans more accessible to water in the three-dimensional structure of this protein.     

Design of novel,simple, and inexpensive 3D printing-based miniaturized electrochemical platform containing embedded disposable detector for analytical applications

This paper describes the development of a novel, simple, and inexpensive electrochemical device containing an integrated and disposable three-electrode system for detection. The base of this platform consists on a PDMS structure containing microchannels which were prototyped using 3D-printed molds. Pencil graphite leads were inserted into these microchannels and utilized as working, counter and reference electrodes in a novel design. Morphological analysis and electrochemical experiments with benchmark redox probes were carried out in order to evaluate the performance and characterize the miniaturized device proposed. Even using inexpensive materials and a simple fabrication protocol, the electrochemical platform developed provided good repeatability and reproducibility over a low cost (ca. $2 per device), acceptable lifetime (ca. 250 voltammetric runs) and extremely reduced consumption of samples and reagents (order of µL). As proof of concept, the analytical feasibility of the platform was investigated through the simultaneous determination of dopamine (DOPA) and acetaminophen (AC). The two analytes showed linear dependence on the concentration range from 1 to 15 µM and the LODs achieved were 0.21 µM for DOPA and 0.29 µM for AC. Moreover, the platform was successfully applied on the determination of DOPA and AC in spiked blood serum and urine samples. The results obtained with the device described here were better than some reports in literature that use more costly electrodic materials and complex modification steps for the detection of the same analytes.     

Adaptive smooth control for nonlinear uncertain systems

Nonlinear Dynamics - This paper presents an adaptive smooth controller for a class of nonlinear dynamical systems in the presence of bounded uncertainties with unknown bounds. Motivated by the...     

Photocatalyzed Intramolecular [2+2] Cycloaddition of N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides

N-Alkyl-N-(2-(1-arylvinyl)aryl)cinnamamides are converted into natural product inspired scaffolds via iridium photocatalyzed intramolecular [2+2] photocycloaddition. The protocol has a broad substrate scope, whilst operating under mild reaction conditions. Tethering four components forming a trisubstituted cyclobutane core builds rapidly high molecular complexity. Our approach allows the design and synthesis of a variety of tetrahydrocyclobuta[c]quinolin-3(1H)-ones, in yields ranging between 20–99 %, and with excellent regio- and diastereoselectivity. Moreover, it was demonstrated that the intramolecular [2+2]-cycloaddition of 1,7-enynes—after fragmentation of the cyclobutane ring—leads to enyne-metathesis-like products.