Influence of thiolate ligands on reductive N-O bond activation. Probing the O2(-) binding site of a biomimetic superoxide reductase analogue and examining the proton-dependent reduction of nitrite

Nitric oxide (NO) is frequently used to probe the substrate-binding site of "spectroscopically silent" non-heme Fe(2+) sites of metalloenzymes, such as superoxide reductase (SOR). Herein we use NO to probe the superoxide binding site of our thiolate-ligated biomimetic SOR model [Fe(II)(S(Me(2))N(4)(tren))](+) (1). Like NO-bound trans-cysteinate-ligated SOR (SOR-NO), the rhombic S = 3/2 EPR signal of NO-bound cis-thiolate-ligated [Fe(S(Me(2))N(4)(tren)(NO)](+) (2; g = 4.44, 3.54, 1.97), the isotopically sensitive ν(NO)(ν((15)NO)) stretching frequency (1685(1640) cm(-1)), and the 0.05 ? decrease in Fe-S bond length are shown to be consistent with the oxidative addition of NO to Fe(II) to afford an Fe(III)-NO(-) {FeNO}(7) species containing high-spin (S = 5/2) Fe(III) antiferromagnetically coupled to NO(-) (S = 1). The cis versus trans positioning of the thiolate does not appear to influence these properties. Although it has yet to be crystallographically characterized, SOR-NO is presumed to possess a bent Fe-NO similar to that of 2 (Fe-N-O = 151.7(4)°). The N-O bond is shown to be more activated in 2 relative to N- and O-ligated {FeNO}(7) complexes, and this is attributed to the electron-donating properties of the thiolate ligand. Hydrogen-bonding to the cysteinate sulfur attenuates N-O bond activation in SOR, as shown by its higher ν(NO) frequency (1721 cm(-1)). In contrast, the ν(O-O) frequency of the SOR peroxo intermediate and its analogues is not affected by H-bonds to the cysteinate sulfur or other factors influencing the Fe-SR bond strength; these only influence the ν(Fe-O) frequency. Reactions between 1 and NO(2)(-) are shown to result in the proton-dependent heterolytic cleavage of an N-O bond. The mechanism of this reaction is proposed to involve both Fe(II)-NO(2)(-) and {FeNO}(6) intermediates similar to those implicated in the mechanism of NiR-promoted NO(2)(-) reduction.     

On-line sample preparation for high throughput reversed-phase LC/MS analysis of combinatorial chemistry libraries

An on-line sample preparation method utilizing a time-programmed autosampler is described for high throughput liquid chromatography/mass spectrometry (LC/MS). This approach is particularly helpful for the LC/MS analysis of samples which require solvents incompatible with HPLC in the sample preparation process. The on-line sample preparation approach minimizes a bottleneck in throughput and improves sample recovery under some circumstances.     

Synthesis of an arylene/alkylene polyether from diphenolic acid and rosenmund reduction to the polyether aldehyde

The Williamson ether synthesis has been applied to the formation of an arylene/alkylene polyether with pendant carboxyl groups from 4,4-bis(p-hydroxyphenyl)pentanoic acid and 1,4-dichlorobutane. The polymer was found to have a viscosity—molecular weight relationship following the equation, [η] = 1.30 × 10^?4M^0.94, in dimethylformamide at 25°C. Hydrogenolysis of the derived polyether acid chloride was found to proceed smoothly at atmospheric pressure in the presence of Pd–BaSO₄ catalyst without poisoning of the catalyst by multiple absorption of polymer. The resulting polyether aldehyde undergoes typical aldehyde reactions. The infrared spectra of the polymers are also examined.     

A novel approach to high-throughput quality control of parallel synthesis libraries

Combinatorial chemistry is a powerful tool to enhance drug discovery efforts in the pharmaceutical industry. One type of combinatorial chemistry, parallel synthesis, is now widely used to prepare numerous compounds of structural diversity. A novel high-throughput method for quality control of parallel synthesis libraries has been developed. The method uses flow injection MS, for proof of structure and estimation of purity, and a novel direct injection CLND technique for quantitation of amount. Following the synthesis of a small molecule library, compounds analyzed using this technique were characterized by mass spectrometry, and an accurate concentration of the compound was assessed by CLND. Characterization of one compound is completed in 60 s, allowing for up to 1000 compounds to be analyzed in a single day. The data is summarized using pass/fail criteria using internally developed software.     

Tartaric acid-derived chiral phosphite-type P,N-ligands: behavioural features in Pd-catalyzed asymmetric transformations

A practical synthesis of new phosphoramidite, phosphite and diamidophosphite P,N-ligands derived from (R,R)-tartaric acid was carried out. A study of these chiral inducers showed them to provide up to 93% ee in the Pd-catalyzed asymmetric allylations of (E)-1,3-diphenylallyl acetate, up to 84% ee in the Pd-catalyzed asymmetric alkylation of cinnamyl acetate with ethyl 2-oxocyclohexane-1-carboxylate and up to 63% ee in the Pd-catalyzed desymmetrization of N,N′-ditosyl-meso-cyclopent-4-ene-1,3-diol biscarbamate. The effects of the structural modules, such as the nature of the phosphorus-containing ring or exocyclic substituent as well as of the nature of palladium source on the catalytic activity and enantioselectivity were investigated.     

Dilepton and trilepton production by antineutrinos and neutrinos in neon

A sample of over 25,000 fully measured neutrino and antineutrino charged current interactions in BEBC includes 192 dilepton candidates. The prompt signal after subtraction of background is 41 ±7µ⁺ e ^-, 35±7µ⁺µ^- events from \(\bar v\) interactions, and 32±7µ^-µ⁺ events from ν interactions. There are 2 trileptons, µ^-µ^- e ⁺ and µ^-µ^-µ⁺. Results are compared with other experimental data and with the standard model. Limits to prompt like sign µ⁺ e ⁺, µ⁺µ⁺ and µ^-µ^- signals are given and compared with other experiments and with theoretical calculations.     

Analytical methods for quality control of combinatorial libraries

This literature review covers the applications of analytical techniques to solid phase organic chemistry and combinatorial chemistry published between June 96 and September 1997. Highlighted are mass spectrometry, NMR, IR and chromatographic analyses of solid phase synthesis reactions and combinatorial libraries.