Proton to carbon-13 INEPT in solid-state NMR spectroscopy

A refocused INEPT through-bond coherence transfer technique is demonstrated for NMR of rigid organic solids and is shown to provide a valuable building block for the development of NMR correlation experiments in biological solids. The use of efficient proton homonuclear dipolar decoupling in combination with a direct spectral optimization procedure provides minimization of the transverse dephasing of coherences and leads to very efficient through-bond (1)H-(13)C INEPT transfer for crystalline organic compounds. Application of this technique to 2D heteronuclear correlation spectroscopy leads to up to a factor of 3 increase in sensitivity for a carbon-13 enriched sample in comparison to standard through-bond experiments and provides excellent selectivity for one-bond transfer. The method is demonstrated on a microcrystalline sample of the protein Crh (2 x 10.4 kDa).     

Total synthesis of (+)-zaragozic acid C

A total synthesis of (+)-zaragozic acid C is described. Key features of the synthesis are the use of a double Sharpless asymmetric dihydroxylation reaction of diene 6 to control stereochemistry at four contiguous stereocenters from C3 to C6; the introduction of the C1-side chain by reaction between the anion derived from the dithiane monosulfoxide 27 and the core aldehyde 12; a high yielding, acid-mediated simultaneous acetonide deprotection-dithiane removal-ketalization procedure leading exclusively to the 2, 8-dioxabicyclo[3.2.1]octane core 34; and a novel triple oxidation procedure allowing installation of the tricarboxylic acid.     

Thermal activation of molecularly-wired gold nanoparticles on a substrate as catalyst

The ability to prepare nanostructured metal catalysts requires the ability to control size and interparticle spatial and surface access properties. In this work, we report novel findings of an atomic force microscopic investigation of a controlled thermal activation strategy of gold catalysts nanostructured via molecular wiring or linking on a substrate surface. Gold nanocrystals of approximately 2 nm diameter capped by decanethiolate and wired by 1,9-nonanedithiolate on mica substrates were studied as a model system. By manipulating the activation temperature (200-250 degrees C), the capping/wiring molecules can be removed to produce controllable particle size and interparticle spatial morphology. The electrocatalytic activity of the activated nanostructures toward methanol oxidation, which is of fundamental importance to fuel cell catalysis, has been demonstrated. The novelty of the findings is the viability of a thermal activation strategy of core-shell nanostructured catalysts based on molecularly predefined interparticle spatial properties on a substrate, which upon further investigation may form the basis for spatially controllable nanostructured catalysts.     

Alkylation of heme by the antimalarial drug artemisinin

The peroxide function of artemisinin has been activated by iron(II)-heme generated in situ from iron(III)-protoporphyrin-IX and glutathione, a biologically relevant reductant. In mild conditions, this reaction produced a high yield (85%) of heme derivatives alkylated at alpha-, beta-, and delta-meso positions by a C4-centered radical derived from artemisinin.     

Determination of total mercury in environmental and biological samples by flow injection cold vapour atomic absorption spectrometry

A simple and accurate method has been developed for the determination of total mercury in environmental and biological samples. The method utilises an off-line microwave digestion stage followed by analysis using a flow injection system with detection by cold vapour atomic absorption spectrometry.

The method has been validated using two certified reference materials (DORM-1 dogfish and MESS-2 estuarine sediment) and the results agreed well with the certified values. A detection limit of 0.2 ng g⁻¹ Hg was obtained and no significant interference was observed. The method was finally applied to the determination of mercury in river sediments and canned tuna fish, and gave results in the range 0.1–3.0 mg kg⁻¹.     

Kinetic isotope effects implicate the iron-oxene as the sole oxidant in P450-catalyzed N-dealkylation

Multiple oxidants have been implicated as playing a role in cytochrome P450-mediated oxidations. Herein, we report results on N-dealkylation, one of the most facile reactions mediated by P450 enzymes. We have employed the N-oxides of a series of para-substituted 13C2H2-labeled N,N-dimethylanilines to function as both substrates and surrogate oxygen atom donors for P450cam and P4502E1. Kinetic isotope effect profiles obtained using the N-oxide system were found to closely match the profiles produced using the complete NAD(P)H/NAD(P)-P450 reductase/O2 system. The results are consistent with oxidation occurring solely through an iron-oxene species.     

Novel estradiol derivatives labeled with Ru,W, and Co complexes. Influence on hormone-receptor affinity of several organometallic groups at the 17 alpha position

In order to elucidate the extent to which recognition of the estrogen receptor is influenced by addition of an organometallic substituent at the 17 alpha position, modification of 17 beta-estradiol at this position was carried out by using the organometallic groups -C identical to C(eta 5-C5H4)RuCp, CH2-(eta 5-C5H4)RuCp, -C identical to C-(eta 5-C5H4)-W(CO)3(Me), -(C identical to CCHO)Co2(CO)6, and -(C identical to CCH2OH)Co2(CO)6. The relative binding affinity (RBA) values for estradiol receptor alpha showed that recognition was good (RBA between 20 and 13.5%) when the organometallic moiety was attached at the end of a rigid alkyne spacer. However, the affinity of the modified hormone for the receptor was severely reduced (RBA = 1%) for a substituent such as -CH2-(eta 5-C5H4)RuCP, in which the spacer is reduced to a single flexible sp3 carbon atom, allowing the organometallic moiety greater freedom of movement around the attachment point. The RBA values found were in agreement with results obtained from a molecular-modeling study in which 5, an organometallic hormone with a rigid spacer, or 7, a molecule with a flexible spacer, was inserted into the cavity of the recently characterized Ligand-Binding Domain of estrogen receptor alpha.     

Ammonia chemical ionization tandem mass spectrometry in structural determination of alkaloids. II. Tetraponerines from pseudomyrmecine ants

Chemical ionization tandem mass spectrometry (CI-MS/MS) of alkaloids with ammonia reagent gas and collision-activated dissociation as well as EI-MS/MS were applied to the tetraponerine alkaloids in extracts from six pseudomyrmecine ants of the genus Tetraponera. The MS/MS techniques along with gas chromatography Fourier transform infrared (GC/FTIR) spectra allowed identification in two extracts of seven of the eight known tetraponerines. The EI-MS/MS fragmentations proved diagnostic for the ring system and the CI-MS/MS patterns for the C-8 or C-9 substitution, while the Bohlmann bands in FTIR spectra were diagnostic for the C-8 or C-9 configurations. An Indian ant (T. allaborans) had T-2, T-4 and T-8, while a Chinese ant (T. binghami) had T-5, T-6, T-7 and T-8. Four other ants, T. rufonigra (India), T. penzigi (Africa), T. clypeata (Africa) and T. sp. cf. emeryi (Africa), had no tetraponerines.     

Protection against photoaging in the hairless mouse by the isoflavone equol

Topical application of the isoflavone equol immediately following solar-simulated UV (SSUV) radiation exposure has previously been demonstrated to have significant photoprotective effects. Equol reduced both the inflammatory edema and the systemic suppression of the contact hypersensitivity reaction in hairless mice. Furthermore, daily topical equol application immediately following irradiation during a 10-week chronic SSUV exposure regime also reduced photocarcinogenesis severity in the mouse. This study examines the potential for topical equol to prevent photoaging in response to chronic SSUV irradiation for up to 30 weeks. We did not find consistent expression of the characteristic markers of photoaging until 30 weeks, although moderate epidermal hyperplasia and a transient increase in dermal mast cell numbers were evident after 1 week. Daily application of 10 muM equol lotion significantly reduced these early changes. However after 30 weeks of SSUV exposure, photoaging was well developed, as shown histologically by markedly increased epidermal hyperplasia, increased dermal mast cell number, pronounced focal elastotic deposits, degraded dermal collagen and deposition of glycosaminoglycans in the lower dermis. Topical equol treatment protected significantly from each of these impairments, as demonstrated histologically and quantitatively. Additionally, equol was found to have strong antioxidant action against acute UVA (320-400 nm)-induced lipid peroxidation of mouse skin, this property accounting for its antiphotoaging mechanism. The evidence for equol's antiphotoaging activity, taken together with its anti-inflammatory, immunoprotective and anticarcinogenic efficacy against SSUV irradiation in the mouse, suggests that equol could be developed as a helpful topical photoprotective agent for daily use by humans.     

Sterically controlled reductive oligomerisations of CO by activated magnesium(i) compounds: deltate vs. ethenediolate formation

An extremely bulky, symmetrical three-coordinate magnesium(i) complex, [{(^TCHPNacnac)Mg}₂] (^TCHPNacnac = [{(TCHP)NCMe}₂CH]⁻, TCHP = 2,4,6-tricyclohexylphenyl) has been prepared and shown to have an extremely long Mg–Mg bond (3.021(1) Å) for such a complex. It was shown not to react with either DMAP (4-dimethylaminopyridine) or CO. Three unsymmetrical 1 : 1 DMAP adducts of less bulky Mg–Mg bonded species have been prepared, viz. [(^ArNacnac)Mg–Mg(DMAP)(^ArNacnac)] (^ArNacnac = [(ArNCMe)₂CH]⁻ Ar = 2,6-xylyl (Xyl), mesityl (Mes) or 2,6-diethylphenyl (Dep)), and their reactivity toward CO explored. Like the previously reported bulkier complex, [(^DipNacnac)Mg–Mg(DMAP)(^DipNacnac)] (Dip = 2,6-diisopropylphenyl), [(^DepNacnac)Mg–Mg(DMAP)(^DepNacnac)] reductively trimerises CO to give a rare example of a deltate complex, [{(^DepNacnac)Mg(μ-C₃O₃)Mg(DMAP)(^DepNacnac)}₂]. In contrast, the two smaller adduct complexes react with only two CO molecules, ultimately giving unusual ethenediolate complexes [{(^ArNacnac)Mg{μ-OC(H) C(DMAP^−H)O}Mg(^ArNacnac)}₂] (Ar = Xyl or Mes). DFT calculations show the latter reactions to proceed via reductive dimerizations of CO, and subsequent intramolecular C–H activation of Mg-ligated DMAP by “zig–zag” [C₂O₂]²⁻ fragments of reaction intermediates. Calculations also suggest that magnesium deltate complexes are kinetic products in these reactions, while the magnesium ethenediolates are thermodynamic products. This study shows that subtle changes to the bulk of the reacting 1 : 1 DMAP–magnesium(i) adduct complexes can lead to fine steric control over the products arising from their CO reductive oligomerisations. Furthermore, it is found that the more activated nature of the adduct complexes, relative to their symmetrical, three-coordinate counterparts, [{(^ArNacnac)Mg}₂], likely derives more from the polarisation of the Mg–Mg bonds of the former, than the elongated nature of those bonds.

Subtle changes to the bulk of 1 : 1 adducts of DMAP with magnesium(i) complexes leads to steric control over the products arising from their reductive oligomerisations of carbon monoxide.