New and highly efficient synthesis of 3-substituted 1-hydroxybenz[g]isoquinoline-5,10-diones

A new and efficient strategy for the synthesis of 3-substituted 1-hydroxybenz[g]isoquinoline-5,10-diones by reaction of 2-methoxycarbonyl-1,4-naphthoquinone with different pyridinium salts under Kröhnke conditions is disclosed. This one-step reaction was found to be dependent on the substitution pattern of the aromatic nucleus in the pyridinium salts.     

Designed Topology and Site‐Selective Metal Composition in Tetranuclear [MM′⋅⋅⋅M′M] Linear Complexes

The ligand 1,3‐bis[3‐oxo‐3‐(2‐hydroxyphenyl)propionyl]benzene (H₄L), designed to align transition metals into tetranuclear linear molecules, reacts with M^II salts (M=Ni, Co, Cu) to yield complexes with the expected [MM???MM] topology. The novel complexes [Co₄L₂(py)₆] ( 2 ; py=pyridine) and [Na(py)₂][Cu₄L₂(py)₄](ClO₄) ( 3 ) have been crystallographically characterised. The metal sites in complexes 2 and 3 , together with previously characterised [Ni₄L₂(py)₆] ( 1 ), favour different coordination geometries. These have been exploited for the deliberate synthesis of the heterometallic complex [Cu₂Ni₂L₂(py)₆] ( 4 ). Complexes 1 , 2 , 3 and 4 exhibit antiferromagnetic interactions between pairs of metals within each cluster, leading to S=0 spin ground states, except for the latter cluster, which features two quasi‐independent S=1/2 moieties within the molecule. Complex 4 gathers the structural and physical conditions, thus allowing it to be considered as prototype of a two‐qbit quantum gate.     

Disruption of DNA repair processes by carcinogenic metal compounds

Based on pronounced enhancing effects in combination with other DNA-damaging agents the potentials of Ni(II), Cd(II) and As(III) to interfere with DNA repair processes in HeLa cells was investigated. With respect to oxidative DNA damage, Ni(II) and Cd(II) induced DNA strand breaks starting at concentrations of 250 μM and 5 μM, respectively. The induction of oxidative DNA base modifications like 8-hydroxyguanine was restricted to the cytotoxic concentration of 750 μM Ni(II) and not observed after treatment with Cd(II). In contrast, the removal of oxidative DNA base modifications was inhibited at concentrations as low as 50 μM Ni(II) and 0.5 μM Cd(II). Regarding nucleotide excision repair, Ni(II) and Cd(II) disturbed the DNA-protein interactions involved in the damage recognition step when applying HeLa nuclear protein extracts and a UV-damaged oligonucleotide, while As(III) inhibited the actual incision event. In the case of Ni(II) and Cd(II), this effect was reversible by the addition of Mg(II) and Zn(II), respectively. Furthermore, Cd(II) inactivated the isolated bacterial Fpg protein, most likely by the displacement of Zn(II) from its zinc finger structure. Since DNA is continuously damaged by exogenous and endogenous sources, an impaired repair capacity might well account for the carcinogenic action of the metal compounds. Received: 30 July 1997 / Revised: 6 October 1997 / Accepted: 10 October 1997     

Method for the direct determination of available carbohydrates in low-carbohydrate products using high-performance anion exchange chromatography

An improved method for direct determination of available carbohydrates in low-level products has been developed and validated for a low-carbohydrate soy infant formula. The method involves modification of an existing direct determination method to improve specificity, accuracy, detection levels, and run times through a more extensive enzymatic digestion to capture all available (or potentially available) carbohydrates. The digestion hydrolyzes all common sugars, starch, and starch derivatives down to their monosaccharide components, glucose, fructose, and galactose, which are then quantitated by high-performance anion-exchange chromatography with photodiode array detection. Method validation consisted of specificity testing and 10 days of analyzing various spike levels of mixed sugars, maltodextrin, and corn starch. The overall RSD was 4.0% across all sample types, which contained within-day and day-to-day components of 3.6 and 3.4%, respectively. Overall average recovery was 99.4% (n = 10). Average recovery for individual spiked samples ranged from 94.1 to 106% (n = 10). It is expected that the method could be applied to a variety of low-carbohydrate foods and beverages.     

Syntheses and excitation transfer studies of near-orthogonal free-base porphyrin-ruthenium phthalocyanine dyads and pentad

A new series of molecular dyads and pentad featuring free-base porphyrin and ruthenium phthalocyanine have been synthesized and characterized. The synthetic strategy involved reacting free-base porphyrin functionalized with one or four entities of phenylimidazole at the meso position of the porphyrin ring with ruthenium carbonyl phthalocyanine followed by chromatographic separation and purification of the products. Excitation transfer in these donor-acceptor polyads (dyad and pentad) is investigated in nonpolar toluene and polar benzonitrile solvents using both steady-state and time-resolved emission techniques. Electrochemical and computational studies suggested that the photoinduced electron transfer is a thermodynamically unfavorable process in nonpolar media but may take place in a polar environment. Selective excitation of the donor, free-base porphyrin entity, resulted in efficient excitation transfer to the acceptor, ruthenium phthalocyanine, and the position of imidazole linkage on the free-base porphyrin could be used to tune the rates of excitation transfer. The singlet excited Ru phthalocyanine thus formed instantly relaxed to the triplet state via intersystem crossing prior to returning to the ground state. Kinetics of energy transfer (k(ENT)) was monitored by performing transient absorption and emission measurements using pump-probe and up-conversion techniques in toluene, respectively, and modeled using a F?rster-type energy transfer mechanism. Such studies revealed the experimental k(ENT) values on the order of 10(10)-10(11) s(-1), which readily agreed with the theoretically estimated values. Interestingly, in polar benzonitrile solvent, additional charge transfer interactions in the case of dyads but not in the case of pentad, presumably due to the geometry/orientation consideration, were observed.     

Tuning the Photocatalytic Activity of CdS Nanocrystals through Intermolecular Interactions in Ionic‐Liquid Solvent Systems

Synthetic solvent systems for the fine‐tuned preparation of CdS nanocrystallites, active in visible‐light photocatalytic hydrogen production, were studied. To control crystallite size and spectral properties, the CdS crystals were synthesised by using different solvent systems, containing a series of tetrabutylammonium amino carboxylate ionic liquids as the crystal‐growth control agents. Six samples of CdS, all with similar physical and spectral properties, exhibited greatly varying photocatalytic activity, with the most active sample outperforming the least active one by almost 60 %. To rationalise this effect, the intermolecular interactions of the synthesis solvent system with the growing CdS nanocrystallites were characterised by using the Reichart betaine dye and the ${E{{{\rm N}\hfill \atop {\rm T}\hfill}}}$ polarity scale. A correlation was observed between the ${E{{{\rm N}\hfill \atop {\rm T}\hfill}}}$ values of the solvent system and the photocatalytic activity of the CdS nanocrystallite, suggesting that the hydrogen‐bond‐donating ability and/or dipolarity/polarisability interactions of the solvent system led to the preferential formation of active surfaces/surface sites on the CdS crystals.     

The bromopentadienyl acrylate approach to himbacine

[reaction: see text] The syntheses of 4,4a-didehydrohimbacine and 4,4a-didehydrohimandravine are presented. Key steps include an intramolecular Diels-Alder reaction of a bromopentadienyl acrylate and Suzuki-Miyaura and Stille coupling reactions.     

Evaluation of complexes of DNA duplexes and novel benzoxazoles or benzimidazoles by electrospray ionization mass spectrometry

Electrospray ionization mass spectrometry is used to compare the metal ion binding and metal-mediated DNA binding of benzoxazole (1, 2, 3, 4) and benzimidazole (5) compounds and to elucidate the putative binding modes and stoichiometries. The observed metal versus non-metal-mediated DNA binding, as well as the specificity of DNA binding, is correlated with the biological activities of the analogs. The ESI-MS spectra for the antibacterial benzoxazole and benzimidazole analogs 4 and 5 demonstrated non-specific and non-metal-mediated binding to DNA, with the appearance of DNA complexes containing multiple ligands. The anticancer analog 2 demonstrates a clear preference for metal-mediated DNA interactions, with an apparent selectivity for Ni2+ -mediated binding over the more physiologically relevant Mg2+ or Zn2+ cations. Complexation between DNA and the biologically inactive analog 1 was not observed, either in the absence or presence of metal cations.     

Programmable large area digital microfluidic array with integrated droplet sensing for bioassays

We describe a new device concept for digital microfluidics, based on an active matrix electrowetting on dielectric (AM-EWOD) device. A conventional EWOD device is limited by the number of electrical connections that can be made practically, which restricts the number and type of droplet operations. In an AM-EWOD, the patterned electrodes of a conventional EWOD device are replaced by a thin film transistor (TFT) array, as found in a liquid crystal display (LCD), facilitating independent control of each electrode. The arrays can have many thousand individually addressable electrodes, are fully reconfigurable and can be programmed to support multiple simultaneous operations. Each element is 210 μm × 210 μm in size and contains a circuit that measures the electrical impedance of the liquid above it. This is used to determine the presence and size of a droplet, a method that can improve assay reliability and accuracy. This sensor provides feedback, error detection and closed loop control of an assay sequence. We describe the design, fabrication and testing of a 64 × 64 format AM-EWOD device with impedance sensor functionality. A colorimetric assay is implemented on the device and used to measure glucose in human blood serum. Results are compared with the same assay performed on a microtitre plate.