Sequential isomerization and ring-closing metathesis: masked styryl and vinyloxyaryl groups for the synthesis of benzo-fused heterocycles

The use of an aryl allyl ether and an arylallyl group as masked vinyl ether and 1-propenylphenyl groups for ring-closing metathesis (RCM) leading to the synthesis of benzo-fused heterocycles was demonstrated by using a ruthenium-mediated isomerization followed by a ruthenium-mediated RCM reaction. This resulted in the syntheses of a variety of products including two substituted benzo[1,4]dioxins, a naphtho[2,3-b][1,4]dioxin, a 2H-chromene and a benzo[b]furan.     

Dose and timing of the first light fraction in two-fold illumination schemes for topical ALA-mediated photodynamic therapy of hairless mouse skin

A fractionated illumination scheme in which a cumulative fluence of 100 J cm(-2) is delivered in two equal light fractions separated by a dark interval of 2 h has been shown to considerably increase the efficacy of 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT). The efficacy of such a scheme is further increased if the fluence of the first light fraction is reduced to 5 J cm(-2). We have investigated the relationship between the PDT response and the kinetics of protoporphyrin IX (PpIX) fluorescence in the SKH1 HR hairless mouse for first fraction fluences below 5 J cm(-2) delivered 4 h after the application of ALA and 10 J cm(-2) delivered 2 h after the application of ALA. Illumination is performed using 514 nm at a fluence rate of 50 mW cm(-2). Reducing the fluence of the first fraction to 2.5 J cm(-2) does not result in significantly different visual skin damage. The PDT response, however, is significantly reduced if the fluence is lowered to 1 J cm(-2), but this illumination scheme (1 + 99 J cm(-2)) remains significantly more effective than a single illumination of 100 J cm(-2). A first light fraction of 10 J cm(-2) can be delivered 2 h earlier, 2 h after the application of ALA, without significant reduction in the PDT response compared with 5 + 95 J cm(-2) delivered 4 and 6 h after the application of ALA. The kinetics of PpIX fluorescence are consistent with those reported previously by us and do not explain the significant increase in PDT response with a two-fold illumination scheme. Histological sections of the illuminated volume showed a trend toward increasing extent and depth of necrosis for the two-fold illumination scheme in which the first light fraction is 5 J cm(-2), compared with a single illumination scheme.     

Product distribution of peroxynitrite decay as a function of pH, temperature, and concentration.

The decay of peroxynitrite [O=NOO(-), oxoperoxonitrate(1-)] was examined as a function of concentration (0.050-2.5 mM), temperature (5-45 degrees C), and pH (2.2-10.0). Below 5 degrees C and pH 7, little amounts of the decomposition products nitrite and dioxygen are formed, even when the peroxynitrite concentration is high (2.5 mM). Instead, approximately > or =90% isomerizes to nitrate. At higher pH, decomposition increases at the expense of isomerization, up to nearly 80% at pH 10.0 at 5 degrees C and 90% at 45 degrees C. Much less nitrite and dioxygen per peroxynitrite are formed when the peroxynitrite concentration is lower; at 50 microM and pH 10.2, < or =40% decomposes. In contrast to two other reports (Pfeiffer, S.; Gorren, A. C. F.; Schmidt, K.; Werner, E. R.; Hansert, B.; Bohle, D. S.; Mayer, B. J. Biol. Chem. 1997, 272, 3465-3470, and Coddington, J. W.; Hurst, J. K.; Lymar, S. V. J. Am. Chem. Soc. 1999, 121, 2438-2443), we find that the extent of decomposition is dependent on the peroxynitrite concentration.     

A solvent-controlled switch of manganese complex assemblies with a beta-diketonate-based ligand

The coordination properties of the new polynucleating ligand H(3)L1 (1,3-bis(3-oxo-3-phenylpropionyl)-2-hydroxy-5-methylbenzene) with Mn(II/III) are described. Depending on the solvent used, the reaction of H(3)L1 with Mn(OAc)(2) yields either of the two new multinuclear assemblies [Mn(2)(HL1)(2)(py)(4)] (1) and [Mn(3)(HL1)(3)] (2), as revealed by X-ray crystallography. The structure of 2 is remarkable in that it shows a unique asymmetric triple-stranded helicate. Complexes 1 and 2 can be interconverted by controlling the solvent of the reaction system, and therefore, this ensemble constitutes an interesting externally addressable switch. In the presence of Mn(III)/pyridine, partial degradation of H(3)L1 occurs via oxidative cleavage, and the new complex [Mn(2)(L2)(2)(py)(4)] (3) is formed. The crystal structure of this complex has shown the fully deprotonated form of the new donor H(3)L2 (3-(3-oxo-3-phenylpropionyl)-5-methylsalicylic acid). From the same reaction, the Mn(II) complex 1 is also obtained. A rational synthesis of H(3)L2 is reported, and this has been used to prepare 3 in high yields, directly from its components. Variable-temperature magnetic susceptibility (chi(m)) measurements were performed on complexes 1-3 under a magnetic field of 1 kG. The data for each complex were fit to the appropriate chi(m) vs T theoretical equation, respectively. In 1, the Mn(II) ions are uncoupled, with g = 2.01. The data from 2 were fit by assuming the presence of an exchange coupled Mn(II)...Mn(II) pair next to a magnetically isolated Mn(II) center. The fit gave J = -2.75 cm(-1), g(12) = 1.97, and g(3) = 1.92, respectively. In 3, two models fit the experimental data. In the most satisfactory, the Mn(III) ions are coupled antiferromagnetically with J = -1.48 cm(-1) and g = 1.98 and a term for weak ferromagnetic intermolecular exchange is included with zJ' = 0.39 cm(-1). The other model contemplates the presence of two uncoupled zero field split Mn(III) ions.     

Time-resolved fluorescence analysis of the mobile flavin cofactor in p -hydroxybenzoate hydroxylase

Conformational heterogeneity of the FAD cofactor in p-hydroxybenzoate hydroxylase (PHBH) was investigated with time-resolved polarized flavin fluorescence. For binary enzyme/substrate (analogue) complexes of wild-type PHBH and Tyr222 mutants, crystallographic studies have revealed two distinct flavin conformations; the ‘in’ conformation with the isoalloxazine ring located in the active site, and the ‘out’ conformation with the isoalloxazine ring disposed towards the protein surface. Fluorescence-lifetime analysis of these complexes revealed similar lifetime distributions for the ‘in’ and ‘out’ conformations. The reason for this is twofold. First, the active site of PHBH contains various potential fluorescence-quenching sites close to the flavin. Fluorescence analysis of uncomplexed PHBH Y222V and Y222A showed that Tyr222 is responsible for picosecond fluorescence quenching free enzyme. In addition, other potential quenching sites, including a tryptophan and two tyrosines involved in substrate binding, are located nearby. Since the shortest distance between these quenching sites and the isoalloxazine ring differs only little on average, these aromatic residues are likely to contribute to fluorescence quenching. Second, the effect of flavin conformation on the fluorescence lifetime distribution is blurred by binding of the aromatic substrates: saturation with aromatic substrates induces highly efficient fluorescence quenching. The flavin conformation is therefore only reflected in the small relative contributions of the longer lifetimes.     

On the non-existence of a class of symmetric group divisible partial designs

Many non-existence theorems are known for symmetric group divisible partial designs. In the case that these partial designs are auto-dual with ₁=0, an ideal incidence structure can be defined whose elements are the equivalence-classes of non-collinear points and parallel blocks. Except for some trivial cases this incidence structure turns out to be a symmetric design, and by studying its existence we can prove much more powerful non-existence theorems.     

Multi-objective seaport planning by MOORA decision making

An approach is needed to localize in an optimal way a seaport facing different indicators, criteria or objectives sometimes from different groups or individuals. The internal mechanical solution of a Ratio System, producing dimensionless numbers, is preferred to Cost-Benefit or to Weights which most of the time are used to equalize the different units. The ratio system creates the opportunity to use a second approach: a non-subjective Reference Point Theory based on the found ratios. The two approaches form a control on each other. This theory is called MOORA (Multi-Objective Optimization by Ratio Analysis). As an application a ranking is made for the best location of a new seaport or for the expansion of an existing one given a set of objectives to be fulfilled.     

The Oxidation of Thiols by Flavoprotein Oxidases: a Biocatalytic Route to Reactive Thiocarbonyls

Flavoprotein oxidases are a diverse class of biocatalysts, most of which catalyze the oxidation of C? O, C? N, or C? C bonds. Flavoprotein oxidases that are known to catalyze the oxidation of C? S bonds are rare, being limited to enzymes that catalyze the oxidative cleavage of thioethers. Herein, we report that various flavoprotein oxidases, previously thought to solely act on alcohols, also catalyze the oxidation of thiols to thiocarbonyls. These results highlight the versatility of enzymatic catalysis and provide a potential biocatalytic route to reactive thiocarbonyl compounds, which have a variety of applications in synthetic organic chemistry.