Post-Newtonian estimation in relativistic optics

A post-Newtonian analysis of the theory of gravity based on the metricg _ij(x,y)= _ij(x)+/c ²(1–1n ²)y _iy_j with the index of refractionn(x, y) is given. A generalized Lagrange space endowed with this metric is used for the study of gravitational phenomena. The index of refractionn(x, y) is expanded in integer powers of the gravitational potentialU=GM/rc ² andv ²/c ². It is shown that solar system tests impose a constraint on a combination of the constant, the post-Newtonian parameters defining the index of refractionn(x, y), and the post-Newtonian parameter associated to the Riemannian metric _ij(x).     

A new method for reversible immobilization of thiol biomolecules based on solid-phase bound thiolsulfonate groups

A new method for the reversible immobilization of thiol bimolecules, e.g., thiolpeptides and thiolproteins, to beaded agarose and other solid phases is reported. The method consists of an activation and a coupling step. The activation is based on oxidation of disulfides (or thiol groups via disulfides) present in a solid phase by hydrogen peroxide at moderately acidic pH. This oxidation leads to disulfide oxides (thiolsulfinate groups of which the majority are further oxidized to thiolsulfonate). The thiolsulfonate groups react easily with thiol compounds, which become immobilized via disulfide bonds. The pH range for thiol coupling is wide (pH 5-8), but for most thiols the reaction seems to proceed faster at pH>7. The stability of the reactive group to hydrolysis, especially at neutral and weakly acidic pH, is very high. The activated gel, therefore, can be stored as a suspension at pH 5 for extended periods. The method has been used to reversibly immobilize glutathione, β-galactosidase, alcohol dehydrogenase, urease, and papain, all with exposed thiol groups as well as thiolated bovine serum albumin and sweet-potato β-amylase. Depending on the thiol content of starting thiol-agarose, thiol-sulfonate-agarose derivatives with different binding capacities can be obtained. Thus, up to 5.0 mg (16 μmol) glutathione and 15 mg thiol-protein/mL gel derivative have been immobilized.     

Preparation and biological evaluation of key fragments and open analogs of scleritodermin A

The synthesis of key fragments of scleritodermin A, their assembly, and their biological evaluation as cytotoxic and anthelmintic were performed. Highlights of the synthetic route include formation of the α-ketoamide linkage and use of stereocontrolled reactions. Open analogs of this natural product were obtained using a convergent strategy.     

Two natural products from the algae Laurencia scoparia

The structures and absolute stereochemistries of two chamigrene-type metabolites (spiro­[5.5]­un­decane derivatives) isolated from the red algae Laurencia scoparia are described. One, a non-sesquiterpene named ma?lione (8-bromo-9-hydroxy-7,7-di­methyl-11-methyl­ene­spiro­[5.5]­undec-1-en-3-one), C₁₄H₁₉BrO₂, was detected previously in Laurencia cartilaginea, while the other, the sesquiterpene isorigidol (8-bromo-3,7,7-tri­methyl-11-methyl­ene­spiro­[5.5]-undec-1-ene-3,9-diol), C₁₅H₂₃BrO₂, is a new isomer of rigidol, first isolated from Laurencia rigida. The A rings of these spiro­cyclic compounds show the same carbon skeleton. However, the relative stereochemistry of the 8-Br and 9-OH substituents is different. While ma?lione displays the usual syn (or cis) relative stereochemistry of the bromo­hydroxy vicinal group, isorigidol shows an anti (or trans) arrangement. The 8-Br and 9-OH groups are both in equatorial positions in isorigidol, while the 9-OH group is axial in ma?lione, as in most chamigrenes. The absolute configurations of the chiral centers were determined as 6S, 8S and 9R in ma?lione, and 3R, 6S, 8S and 9S in isorigidol.     

An efficient synthesis of 2,4′-bi-1,3-oxa(thia)zoles as scaffolds for bioactive products

A rapid and efficient methodology to prepare 2,4′-bi-1,3-azoles as scaffolds for biologically active marine natural products is described. Hantzsch reaction and oxidative cyclodehydration of β-hydroxy amides or thioamides were used to construct the azole rings. The obtained biheterocycles displayed no cytotoxicity on HCT-15 cell line.     

A novel and easy two-step,microwave-assisted method for the synthesis of halophenyl pyrrolo[2,3-b]quinoxalines via their pyrrolo precursors. Evaluation of their bioactivity

A novel, two-step, facile route for the synthesis of pyrrolo[2,3-b]quinoxalines via 2,3-dioxopyrroles, enhanced by microwave irradiation, is presented. The newly synthesized 2,3-dioxo-5-halophenyl pyrrolo precursors 4a–c as well as the non-aromatized ethyl 2-(4-halophenyl)-1-methyl-2,4-dihydro-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylates 6a–c and the aromatized ethyl 2-(4-halophenyl)-1-methyl-1H-pyrrolo[2,3-b]quinoxaline-3-carboxylates 7a–c were evaluated for their antioxidant, cytostatic, and antiviral properties. Most of them proved to be potent hydroxyl radical scavengers and inhibited in vitro lipid peroxidation. The compounds showed moderate antiproliferative activity, while 6a inhibited vaccinia virus at an EC₅₀ value of 2 μM, and 4c and 6c inhibited Sindbis virus at EC₅₀ values of 4 μM.     

Solid-phase thiolsulfinates for the reversible immobilization of thiols

A new method for the reversible immobilization of thiol-containing substances on agarose beads is presented. It is based on the use of thiolsulfinate (disulfide monoxide) as a solid-phase reactive group. The thiolsulfinate groups are introduced by controlled oxidation of thiol agarose. The method comprises two steps: First, mild oxidation of the agarose thiol groups to disulfide structures with potassium ferricyanide. Second, the oxidation of the so-formed agarose disulfide groups to thiolsulfinate groups by use of a stoichiometric amount of the oxidizing agent magnesium monoperoxyphtalate. The solid-phase thiolsulfinate groups react very easily with thiols, which, as a result of the reaction, will be bound to the agarose beads by disulfide bonds. The adsorbent derivative is very suitable for the reversible immobilization of low as well as high-mol-wt thiols as demonstrated with reduced glutathione, penicillamine, mercaptoethanesulfonic acid, thiolated bovine serum albumin,β-galactosidase, and ±₁-antitrypsine. Since treatment of the agarose derivatives with an excess of low-mol-wt thiols (e.g., dithiothreitol) leads to release of the bound molecules and regeneration of the original thiol groups, the reactive thiolsulfinate groups can easily be regenerated by the mentioned two-step procedure. The cycle of oxidation, binding, reduction, and reoxidation can be performed several times while retaining thiol binding capacity.     

Solid-phase reducing agents as alternative for reducing disulfide bonds in proteins

Disulfide reduction of Kluyveromyces lactis and Aspergillus oryzae β-galactosidases and β-lactoglobulin was assessed. Reduction was performed using one of two thiol-containing agents: dithiothreitol (DTT) or thiopropyl-agarose with a high degree of substitution (1000 μmol of SH groups/g of dried gel). Both reductants allowed an increase of three- (for K. lactis β-galactosidase) and fourfold (for A. oryzae β-galactosidase) in the initial content of SH groups in the lactases. Nearly sevenfold fewer micromoles of SH groups per milligram of protein were needed to perform the reduction of K. lactis β-galactosidase with thiopropyl-agarose than for the same reduction with DTT. However, for A. oryzae β-galactosidase, nearly twice as many micromoles of SH groups per milligram of protein were needed with thiopropylagarose than with DTT. Disulfide bonds in β-lactoglobulin were not accessible to thiopropyl-agarose, since this reduction was only possible in the presence of 6 M urea. These results proved that highly substituted thiopropyl-agarose is as good a reducing agent as DTT, for the reduction of disulfide bonds in proteins. Moreover, excess reducing agent was very simply separated from the reduced protein by filtration, making it easier to control the reaction and providing reduced protein solutions free of reductant. All these advantages substantially cut down the time required and therefore the cost of the overall process.