Metal-ligand charge-transfer-promoted photoelectronic Bergman cyclization of copper metalloenediynes: photochemical DNA cleavage via C-4' H-atom abstraction

Metal-to-ligand charge-transfer (MLCT) photolyses (lambda > or = 395 nm) of copper complexes of cis-1,8-bis(pyridin-3-oxy)oct-4-ene-2,6-diyne (bpod, 1), [Cu(bpod)(2)]PF(6) (2), and [Cu(bpod)(2)](NO(3))(2) (3) yield Bergman cyclization of the bound ligands. In contrast, the uncomplexed ligand 1 and Zn(bpod)(2)(CH(3)COO)(2) compound (4) are photochemically inert under the same conditions. In the case of 4, sensitized photochemical generation of the lowest energy (3)pi-pi state, which is localized on the enediyne unit, leads to production of the trans-bpod ligand bound to the Zn(II) cation by photoisomerization. Electrochemical studies show that 1, both the uncomplexed and complexed, exhibits two irreversible waves between E(p) values of -1.75 and -1.93 V (vs SCE), corresponding to reductions of the alkyne units. Irreversible, ligand-based one-electron oxidation waves are also observed at +1.94 and +2.15 V (vs SCE) for 1 and 3. Copper-centered oxidation of 2 and reduction of 3 occur at E(1/2) = +0.15 and +0.38 V, respectively. Combined with the observed Cu(I)-to-pyridine(pi) MLCT and pyridine(pi)-to-Cu(II) ligand-to-metal charge transfer (LMCT) absorption centered near approximately 315 nm, the results suggest a mechanism for photo-Bergman cyclization that is derived from energy transfer to the enediyne unit upon charge-transfer excitation. The intermediates produced upon photolysis degrade both pUC19 bacterial plasmid DNA, as well as a 25-base-pair, double-stranded oligonucleotide. Detailed analyses of the cleavage reactions reveal 5'-phosphate and 3'-phosphoglycolate termini that are derived from H-atom abstraction from the 4'-position of the deoxyribose ring rather than redox-induced base oxidation.     

Design and synthesis of propeller-shaped dispiroisoxazolinopiperidinochromanones

A library of novel, propeller-shaped dispirotriheterocyclic isoxazolinopiperidinochromanones is reported. Each rigid dispirotriheterocycle was prepared in five linear steps from commercially available tert-butyl 4-oxopiperidine-1-carboxylate and various derivatives of 1-(2-hydroxyphenyl)ethanone, benzaldehyde oxime, and carboxylic acids. Computational chemistry was employed to analyze the three-dimensional geometries of these dispirotriheterocycles, as well as to generate chemoinformatic bioavailability data. X-ray crystallographic structure determination verified the regioselectivity of the nitrile oxide 1,3-dipolar cycloaddition reaction. The resulting library of compounds has been added to the National Institutes of Health repository (approximately 10 mg of each with > or =90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database.     

Fully automated open access platform for rapid, combined serial evaporation and sample reformatting

This paper reports a novel evaporator and its integration with an automated sample handling system to create a high throughput evaporation platform. The Vaportec V-10 evaporator uses a high speed rotation motor ( approximately 6000 rpm) to spin the vial containing a sample, creating a thin film of solvent which can be readily evaporated by the application of heat to the vial, while the consequent centrifugal force prevents "bumping". An intelligent algorithm controls pressure and temperature for optimum solvent removal conditions and end of run detection, critical for automation. The system allows the option of evaporation directly from a sample source vial, or alternatively, integrated liquid handling facilities provide the capability of transferring samples portionwise from a (large) source vial or bottle to a (small) daughter container, enabling efficient sample reformatting, with minimum user intervention. The open access system makes significant advances over current vacuum centrifugal evaporators in terms of evaporation rate and ease of automation. The evaporator's main features, the integration of robotics to provide automation, and examples of evaporation rates of a wide range of solvents from a variety of containers are described.     

Electrocatalytic oxidation of DNA-wrapped carbon nanotubes

The electrical properties of single-walled carbon nanotubes (CNT) are of intense interest due to applications in nanoelectronics. Cyclic voltammetry and chronoamperometry have been used to explore the Ru(bpy)32+ electrocatalytic oxidation of DNA-solubilized carbon nanotubes. Dramatic current enhancements are observed with the addition of a CNT wrapped in an oligonucleotide sequence containing no oxidizable guanines. The current enhancement observed is solely due to the oxidation of the CNT by electrogenerated Ru(III) and subsequent recycling of the metal complex redox reaction. The chronoamperometric (CA) response is biphasic, and rate constants derived from the CA response were used to develop digital simulations of the cyclic voltammograms collected at the same CNT concentrations. Ten successive C' reactions were required to account for all of the observed signal. The oxidation of the CNT is a multielectron process, and this effect arises from the multiple electron donor sites in the carbon nanotube as well as the over oxidation of each site.     

Photo‐Organocatalytic Enantioselective Radical Cascade Reactions of Unactivated Olefins

Radical cascade processes are invaluable for their ability to rapidly construct complex chiral molecules from simple substrates. However, implementing catalytic asymmetric variants is difficult. Reported herein is a visible‐light‐mediated organocatalytic strategy that exploits the excited‐state reactivity of chiral iminium ions to trigger radical cascade reactions with high enantioselectivity. By combining two sequential radical‐based bond‐forming events, the method converts unactivated olefins and α,β‐unsaturated aldehydes into chiral adducts in a single step. The implementation of an asymmetric three‐component radical cascade further demonstrates the complexity‐generating power of this photochemical strategy.     

Amino Acid Assisted Incorporation of Dye Molecules within Calcite Crystals

Biomineralisation processes invariably occur in the presence of multiple organic additives, which act in combination to give exceptional control over structures and properties. However, few synthetic studies have investigated the cooperative effects of soluble additives. This work addresses this challenge and focuses on the combined effects of amino acids and coloured dye molecules. The experiments demonstrate that strongly coloured calcite crystals only form in the presence of Brilliant Blue R (BBR) and four of the seventeen soluble amino acids, as compared with almost colourless crystals using the dye alone. The active amino acids are identified as those which themselves effectively occlude in calcite, suggesting a mechanism where they can act as chaperones for individual molecules or even aggregates of dyes molecules. These results provide new insight into crystal–additive interactions and suggest a novel strategy for generating materials with target properties.     

Direct Measurement of Charge Regulation in Metalloprotein Electron Transfer

Determining whether a protein regulates its net electrostatic charge during electron transfer (ET) will deepen our mechanistic understanding of how polypeptides tune rates and free energies of ET (e.g., by affecting reorganization energy, and/or redox potential). Charge regulation during ET has never been measured for proteins because few tools exist to measure the net charge of a folded protein in solution at different oxidation states. Herein, we used a niche analytical tool (protein charge ladders analyzed with capillary electrophoresis) to determine that the net charges of myoglobin, cytochrome c, and azurin change by 0.62±0.06, 1.19±0.02, and 0.51±0.04 units upon single ET. Computational analysis predicts that these fluctuations in charge arise from changes in the pK_a values of multiple non‐coordinating residues (predominantly histidine) that involve between 0.42–0.90 eV. These results suggest that ionizable residues can tune the reactivity of redox centers by regulating the net charge of the entire protein–cofactor–solvent complex.