Development of carbohydrate-based scaffolds for restricted presentation of recognition groups. Extension to divalent ligands and implications for the structure of dimerized receptors

The solution structure of glycosyl amides has been studied by using NMR. A strong preference is displayed by tertiary aromatic glycosyl amides for E-anti structures in contrast with secondary aromatic glycosyl amides where Z-anti structures predominate. The structural diversity displayed by these classes of molecules would seem to be important as the directional properties of the aromatic ring, or groups attached to the aromatic ring, would be determined by choosing to have either a secondary or tertiary amide at the anomeric center and could be considered when designing bioactive molecules with carbohydrate scaffolds. The structural analysis was also carried out for related divalent secondary and tertiary glycosyl amides and these compounds display preferences similar to that of the monovalent compounds. The constrained divalent compounds have potential for promoting formation of clusters that will have restricted structure and thus have potential for novel studies of mechanisms of action of multivalent ligands. Possible applications of such compounds would be as scaffolds for the design and synthesis of ligands that will facilitate protein-protein or other receptor-receptor interactions. The affinity of restricted divalent (or higher order) ligands, designed to bind to proteins that recognize carbohydrates which would facilitate clustering and concomitantly promote protein-protein interactions, may be significantly higher than monovalent counterparts or multivalent ligands without these properties. This may be useful as a new approach in the development of therapeutics based on carbohydrates.     

Activity coefficients for ternary systems: VI. The system HCl + MgCl2 + H2O at different temperatures; application of Pitzer's equations

Electromotive-force measurements have been made on HCl–MgCl₂–H₂O mixtures at 5, 15, 25, 35 and 45°C at eleven different ionic strengths from 0.1–5.0 mol-kg ^–1 . The results are interpreted in terms of the simple Harned's equations, as well as the more complicated Pitzer ion-component treatment of multicomponent electrolyte mixtures. Activity coefficients for HCl in the salt mixtures obey Harned's rule up to and including I=5.0. For the salt in the acid mixtures, Harned's rule holds true up to and including I=0.5. The contribution of higher-order electrostatic terms (E and E') in the Pitzer equations is important for accurate evaluations of unlike cation-cation interactions (_H,Mg), and cation-anion-cation interactions (_H,Mg,Cl). The values of^S_H,Mg and _H,Mg,Cl (determined with E and E'), _H,Mg and _H,Mg,Cl (determined without E and E'), as well as the trace activity coefficients of HCl, _tr ^A , in solutions of MgCl₂ (where ionic strength fraction of the salt,y _B = 1) at all the experimental temperatures and ionic strengths, are reported. Results of this study are compared with those for similar systems. At I=0.1 and 25°C, the results of the Brönsted-Guggenheim specific interaction theory are discussed briefly.     

On the chemical nature of graphene edges: origin of stability and potential for magnetism in carbon materials

Heretofore disconnected experimental observations are combined with a theoretical study to develop a model of the chemical composition of the edges of graphene sheets in both flat and curved sp(2)-hybridized carbon materials. It is proposed that under ambient conditions a significant fraction of the oxygen-free edge sites are neither H-terminated nor unadulterated sigma free radicals, as universally assumed. The zigzag sites are carbene-like, with the triplet ground state being most common. The armchair sites are carbyne-like, with the singlet ground state being most common. This proposal is not only consistent with the key electronic properties and surface (re)activity behavior of carbons, but it can also explain the recently documented and heretofore puzzling ferromagnetic properties of some impurity-free carbon materials.     

Heats of preferential adsorption of chelates

A method employing a flow calorimeter for determining heats of preferential adsorption of certain organic chelates of metals from organic solutions is described. Experimental heats of adsorption are correlated with the chromatographic behaviour of the chelates and it is shown that irreversible retention on a column occurs when the heat is greater than 6 kcal mole^-1 for the first stage of the two-stage adsorption pro cess. The special case of the 2-methyl-8-quinoline chelate of copper(II) and its elution with solutions of the reagent is examined in more detail: heats of preferential adsorption decrease with increasing concentrations of reagent and the optimum experimental concentration can be predicted from the heat results.     

The application of vinylogous iminium salt derivatives to an efficient synthesis of the pyrrole containing alkaloids Rigidin and Rigidin E

Studies directed on the synthesis of the pyrrole containing marine natural products Rigidin and Rigidin E via vinylogous iminium salts are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole from a vinamidinium salt followed by acylation at the 5-position of pyrrole. Halogenation and aminocarbonylation at the 3-position of pyrrole followed by hydrolysis of the ester group at C-2 and subsequent Curtius rearrangement generates the pyrrolopyrimidine skeleton. A final deprotection step completes the synthesis of Rigidin and Rigidin E.     

DNA binding and photocleavage in vitro by new dirhodium(II) dppz complexes: correlation to cytotoxicity and photocytotoxicity

Two new dirhodium(II) complexes possessing the intercalating dppz ligand (dppz = dipyrido[3,2-a:2',3'-c]phenazine), cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppz)(eta(1)-O(2)CCH(3))(CH(3)OH)](+) (1) and cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppz)(2)](2+) (2), were synthesized and characterized as potential agents for photochemotherapy. Various techniques show that 1 binds to DNA through intercalation, although some aggregation of the complex on the DNA surface is also present. In contrast, 2 does not intercalate between the DNA bases; however, strong hypochromic behavior is observed in the presence of DNA, which can be attributed to intermolecular pi-stacking of 2 enhanced by the polyanion. The apparent DNA binding constants determined using optical titrations are compared to those from dialysis experiments. Both complexes photocleave pUC18 plasmid in vitro under irradiation with visible light (lambda(irr) >or= 395 nm, 15 min), resulting in the nicked, circular form. Greater photocleavage is observed for 1 relative to 2, which may be due to the ability of 1 to intercalate between the DNA bases. The cytotoxicity toward human skin cells (Hs-27) measured as the concentration at which 50% cell death is recorded, LC(50), was found to be 135 +/- 8 microM for 2 in the dark (30 min), which is significantly lower than those of 1 (LC(50) = 27 +/- 2 microM) and Rh(2)(O(2)CCH(3))(4) (LC(50) = 15 +/- 2 microM). Irradiation of cell cultures containing 1 and Rh(2)(O(2)CCH(3))(4) with visible light (400-700 nm, 30 min) has little effect on their cytotoxicity, with LC(50) values of 21 +/- 3 and 13 +/- 2 microM, respectively. Interestingly, a 3.4-fold increase in the toxicity of 2 is observed when the cell cultures are irradiated (400-700 nm, 30 min), resulting in LC(50) = 39 +/- 1 microM. The greater toxicity of 1 compared to 2 in the dark may be related to the ability of the former compound to intercalate between the DNA bases. The lower cytotoxicity of 2, together with its significantly greater photocytotoxicity, makes this complex a potential agent for photodynamic therapy (PDT). These results suggest that intercalation or strong DNA binding may not be a desirable property of a potential PDT agent.     

Permanent Trapping of CO(2) in Single-Walled Carbon Nanotubes Synthesized by the HiPco Process

Infrared spectroscopy is used to study trapped and physisorbed CO2 in single-walled carbon nanotube bundles (SWNTs) synthesized by the HiPco process. CO2 is entrapped within the SWNTs by acid oxidation of the unpurified sample followed by vacuum heating to 700 K. The trapped CO2 has a single nu3 mode at 2327 cm-1, is stable during temperature cycling from 77 to 700 K, and remains after venting to room air. CO2 physisorption studies show a nu3 mode at 2330 cm-1 for the as-received HiPco samples, 2340 cm-1 for the acid-oxidized sample, and 2327 and 2340 cm-1 for the oxidized sample after vacuum heating. The sites responsible for the infrared peaks of the physisorbed and trapped species are discussed.     

Direct DNA photocleavage by a new intercalating dirhodium(II/II) complex: comparison to Rh2(mu-O2CCH3)4

Transition metal complexes possessing the intercalating dppz ligand (dppz = dipyrido[3,2-a:2',3'-c]phenazine) typically bind ds-DNA through intercalation (K(b) approximately 10(5)-10(6) M(-1)), and DNA photocleavage by these complexes with visible light proceeds through the generation of a reactive oxygen species. The DNA binding and photocleavage by [Rh(2)(mu-O(2)CCH(3))(2)(eta(1)-O(2)CCH(3))(CH(3)OH)(dppz)](+) (2) is reported and compared to that of Rh(2)(mu-O(2)CCH(3))(4) (1). Spectral changes and an increase in viscosity provide evidence for the intercalation of 2 to double stranded DNA with K(b) = 1.8 x 10(5) M(-1). DNA photocleavage by 2 is observed upon irradiation with lambda(irr) > 395 nm both in air and deoxygenated solution. DNA photocleavage is not observed for 1 or free dppz ligand under these irradiation conditions. The coupling of a single dppz ligand to a dirhodium(II/II) bimetallic core in 2 provides a means to access oxygen-independent DNA photocleavage with visible light.