Vinyldisiloxanes: their synthesis, cross coupling and applications.

During the studies towards the development of pentafluorophenyldimethylsilanes as a novel organosilicon cross coupling reagent it was revealed that the active silanolate and the corresponding disiloxane formed rapidly under basic conditions. The discovery that disiloxanes are in equilibrium with the silanolate led to the use of disiloxanes as cross coupling partners under fluoride free conditions. Our previous report focused on the synthesis and base induced cross coupling of aryl substituted vinyldisiloxanes with aryl halides; good yields and selectivities were achieved. As a continuation of our research, studies into the factors which influence the successful outcome of the cross coupling reaction with both alkyl and aryl substituted vinyldisiloxanes were examined and a proposed mechanism discussed. Further investigation into expanding the breadth and diversity of substituted vinyldisiloxanes in cross coupling was explored and applied to the synthesis of unsymmetrical trans-stilbenes and cyclic structures containing the trans-alkene architecture.

Directed biosynthesis of phytotoxic alkaloids in the cyanobacterium Nostoc 78-12A.

Nostocarboline, a chlorinated and N-methylated carbolinium alkaloid, displays potent and selective inhibition of photoautotrophic organisms as well as the malaria parasite Plasmodium falciparum, while showing very low toxicity to bacterial and fungal pathogens, rat myoblasts and crustaceans. New derivatives of nostocarboline incorporating Br, F or methyl substituents have been obtained through precursor-directed biosynthesis in Nostoc 78-12A (identical to Nostoc sp. ATCC 43238) by feeding this cyanobacterium with differently substituted tryptophan derivatives or 6-Br-norharmane (eudistomin N). These experiments substantiate the biosynthetic hypothesis and validate the inherent flexibility of the corresponding enzymes for metabolic engineering. The new derivatives inhibit the growth of the toxic-bloom-forming cyanobacterium Microcystis aeruginosa PCC 7806 above 1 microM. The mode of action of nostocarboline was investigated by using chlorophyll-a fluorescence imaging, and it was demonstrated that a decrease in photosynthesis precedes cell death, thus establishing the phytotoxic properties of this alkaloid.

Physicochemical properties of the high-field MRI-relevant [Gd(DTTA-Me)(H2O)2]- complex.

To study the physicochemical properties of the DTTA chelating moiety (H4DTTA = diethylenetriaminetetraacetic acid = N,N'-[iminobis(ethane-2,1-diyl)]bis[N-(carboxymethyl)glycine]), used in several compounds proposed as magnetic resonance imaging (MRI) contrast agents, the methylated derivative H4DTTA-Me (N,N'-[(methylimino)bis(ethane-2,1-diyl)]bis[N-(carboxymethyl)glycine]) was synthesized. Protonation constants of the ligand were determined in an aqueous solution by potentimetry and (1)H NMR pH titration and compared to various DTTA derivatives. Stability constants were measured for the chelates formed with Gd(3+) (log K(GdL) = 18.60 +/- 0.10) and Zn(2+) (log K(ZnL) = 17.69 +/- 0.10). A novel approach of determining the relative conditional stability constant of two paramagnetic complexes in a direct way by (1)H NMR relaxometry is presented and was used for the Gd(3+) complexes [Gd(DTTA-Me)(H2O)2](-) (L1) and [Gd(DTPA-BMA)(H2O)] (L2) [K(L1/L2)*(at pH 8.3, 25 degrees C) = 6.4 +/- 0.3]. The transmetalation reaction of the Gd(3+) complex with Zn(2+) in a phosphate buffer solution (pH 7.0) was measured to be twice as fast for [Gd(DTTA-Me)(H2O)2](-) in comparison to that for [Gd(DTPA-BMA)(H2O)]. This can be rationalized by the higher affinity of Zn(2+) toward DTTA-Me(4-) if compared to DTPA-BMA(3-). The formation of a ternary complex with L-lactate, which is common for DO3A-based heptadentate complexes, has not been observed for [Gd(DTTA-Me)(H2O)2](-) as monitored by (1)H NMR relaxometric titrations. From the results, it was concluded that the heptadentate DTTA-Me(4-) behaves similarly to the commercial octadentate DTPA-BMA(3-) with respect to stability. The use of [Gd(DTTA-Me)(H2O)2](-) as an MRI contrast agent in vitro and in animal studies is conceivable, mainly at high magnetic fields, where an increase of the inner-sphere-coordination water actually seems to be the most certain way to increase the relaxivity.

Intrastrand locks increase duplex stability and base pairing selectivity.

Oligodeoxynucleotide probes with disulfide locks between neighboring nucleobases show increases in melting point for duplexes with RNA target strands of up to 7.6 °C. The weakly pairing TT dimers are replaced with locked 2'-deoxy-5-(thioalkynyl)uridine residues via automated synthesis.