Quantitative analysis of steric effects on the regioselectivity of the Larock heteroannulation reaction.

Alkylphenylacetylene derivatives were synthesized and used as reactants in the Larock heteroannulation reaction to investigate the steric influence on regioselectivity. Large alkyl groups preferentially yielded 2-alkyl-3-phenylindole products, while smaller alkyl groups provided 3-alkyl-2-phenylindole as major products. The logarithm of regioisomeric product ratios exhibited good correlations with various steric parameters. Notably, the Charton values provided the best correlation when excluding the cyclopropyl group. In addition, the Boltzmann-weighted Sterimol parameter (wSterimol) was utilized to generate a good predictive model, indicating the B1 wSterimol as the significant regiochemical determining parameter with no obvious deviation for the cyclopropyl group. Relative atomic distances within the DFT-optimized transition state structures revealed good correlations with the logarithm of regioisomeric ratios. Furthermore, the cyclopropyl adsorption complex indicated electronic contribution, explaining the peculiar behavior of this substituent in the experimental observation.

Dissecting the Electronic Contribution to the Regioselectivity of the Larock Heteroannulation Reaction in the Oxidative Addition and Carbopalladation Steps.

Substituted 2-iodoaniline derivatives were prepared and utilized as reactants, along with asymmetric diarylacetylenes, to synthesize a series of 6-substituted-2,3-diarylindole derivatives via the Larock heteroannulation reaction. Electron-donating substituents on the 2-iodoaniline derivatives retarded the reaction, while electron-withdrawing substituents provided a complete conversion to the indole products. In addition, the electronic properties of the substituted 2-iodoaniline reactants displayed no influence toward regioselectivity. On the contrary, the electronic effect from unsymmetrical diarylacetylenes significantly influenced the regiochemical outcome of the reaction. Density functional theory calculations of the oxidative addition and carbopalladation steps revealed the electronic influences of the substituted 2-iodoaniline derivatives toward the overall rate of the reaction. In contrast, the electronic properties of the asymmetric diarylacetylene remained the critical product-determining factor of regioselectivity.

SAR11 Cells Rely on Enzyme Multifunctionality To Metabolize a Range of Polyamine Compounds.

In the ocean surface layer and cell culture, the polyamine transport protein PotD of SAR11 bacteria is often one of the most abundant proteins detected. Polyamines are organic cations at seawater pH produced by all living organisms and are thought to be an important component of dissolved organic matter (DOM) produced in planktonic ecosystems. We hypothesized that SAR11 cells uptake and metabolize multiple polyamines and use them as sources of carbon and nitrogen. Metabolic footprinting and fingerprinting were used to measure the uptake of five polyamine compounds (putrescine, cadaverine, agmatine, norspermidine, and spermidine) in two SAR11 strains that represent the majority of SAR11 cells in the surface ocean environment, "Candidatus Pelagibacter" strain HTCC7211 and "Candidatus Pelagibacter ubique" strain HTCC1062. Both strains took up all five polyamines and concentrated them to micromolar or millimolar intracellular concentrations. Both strains could use most of the polyamines to meet their nitrogen requirements, but polyamines did not fully substitute for their requirements of glycine (or related compounds) or pyruvate (or related compounds). Our data suggest that potABCD transports all five polyamines and that spermidine synthase, speE, is reversible, catalyzing the breakdown of spermidine and norspermidine, in addition to its usual biosynthetic role. These findings provide support for the hypothesis that enzyme multifunctionality enables streamlined cells in planktonic ecosystems to increase the range of DOM compounds they metabolize. IMPORTANCE Genome streamlining in SAR11 bacterioplankton has resulted in a small repertoire of genes, yet paradoxically, they consume a substantial fraction of primary production in the oceans. Enzyme multifunctionality, referring to enzymes that are adapted to have broader substrate and catalytic range than canonically defined, is hypothesized to be an adaptation that increases the range of organic compounds metabolized by cells in environments where selection favors genome minimization. We provide experimental support for this hypothesis by demonstrating that SAR11 cells take up and metabolize multiple polyamine compounds and propose that a small set of multifunctional enzymes catalyze this metabolism. We report that polyamine uptake rates can exceed metabolic rates, resulting in both high intracellular concentrations of these nitrogen-rich compounds (in comparison to native polyamine levels) and an increase in cell size.

Structure Characterization and Biological Activity of 2-Arylbenzofurans from an Indonesian Plant, Sesbania grandiflora (L.) Pers.

A new 2-arylbenzofuran, sesbagrandiflorain C (1), together with four known compounds, 2-(3,4-dihydroxy-2-methoxyphenyl)-4-hydroxy-6-methoxybenzofuran-3-carbaldehyde (2), 2-(4-hydroxy-2-methoxyphenyl)-5,6-dimethoxybenzofuran-3-carboxaldehyde (3), sesbagrandiflorain A (4) and sesbagrandiflorain B (5), have been isolated from the stem bark of an Indonesian plant, Sesbania grandiflora (L.) Pers. The chemical structure of compound 1 was elucidated by UV, IR, MS, and NMR spectroscopic techniques. The proton and carbon NMR resonances of 1 were also compared with the predicted chemical shifts obtained from DFT quantum mechanical calculations with Gaussian. None of the compounds showed antibacterial activity against Bacillus subtilis, Escherichia coli, Mycobacterium smegmatis, Pseudomonas aeruginosa, and Staphylococcus aureus in an agar diffusion assay. However, sesbagrandiflorains A (4) and B (5) exhibited moderate activity against Mycobacterium tuberculosis H37Rv. In addition, compounds 1 - 5 have moderate cytotoxicity against HeLa, HepG2, and MCF-7 cancer cell lines.

Spectroscopic study of the uranyl-acetohydroxamate adduct with tributyl phosphate.

The ultraviolet-visible (UV-Vis) and Fourier transform infrared (FT-IR) spectroscopic studies carried out for the system UO2(NO3)/AHA/TBP (uranyl-acetohydroxamate-tributyl phosphate) confirmed the presence of the adduct of UO2(NO3)(AHA) 2TBP with 1:1 stoichiometry for UO2:AHA (acetohydroxamic acid). The spectrum of this complex is identical to the infrared spectrum of the organic phase formed in the uranium distribution experiments with 30% TBP/n-dodecane and AHA present in aqueous phase. Disappearance of the hydroxyl stretching band and a shift in the position of the carbonyl band in the infrared spectra revealed that both the hydroxyl and the carbonyl group of acetohydroxamic acid are involved in the chelate ring with uranium. Also, acetic acid, accrued after acidic hydrolysis of acetohydroxamic acid, was identified in the extraction organic phase.

Kinetics and mechanism of rhenium-catalyzed O atom transfer from epoxides.

O atom transfer from epoxides cis-stilbene oxide and styrene oxide to triphenylphosphine catalyzed by Tp'ReO(3) (Tp' = hydridotris(3,5-dimethylpyrazolyl)borate) is shown to proceed via an unexpectedly complex combination of mechanisms. Reduction of Tp'ReO(3) with PPh(3) in THF is rapid above room temperature to form a highly reactive species suggested to be Tp'ReO(2). Spectroscopic examination and attempts to isolate this by chromatography lead only to Tp'Re(O)(OH)(2) (1); exposure of the crude reduction mixture to ethanol results in formation of Tp'Re(O)(OEt)(OH) (3). Both 1 and 3 are as efficient catalysts for O atom transfer as the unpurified mixture resulting from reaction of PPh(3) with Tp'ReO(3); all three rhenium reactants give the same turnover frequency to within 10% at identical [Re](total) and [epoxide]. The kinetic behavior of the catalytic system (epoxide:Re = 20) is complex; an initial "burst" of alkene production is seen, which quickly tapers off and falls into a pseudo-zero-order reaction. The majority of rhenium is observed to exist as the syn-Tp'Re(O)(diolate) complex, formed by ring expansion of the epoxide. However, cycloreversion of this diolate is incapable of accounting for the observed catalytic turnover frequency. An additional intermediate, a coordinated epoxide, is proposed to form and partition between ring expansion and direct fragmentation to alkene; eventually a steady-state concentration of diolate forms. Competition between direct atom transfer and ring expansion followed by diolate cycloreversion is demonstrated by reaction of 3 with excess cis-stilbene oxide and styrene oxide in the absence of reductant to give a 4:1 mixture of alkene and syn-diolate from cis-stilbene oxide or a 5.5:1 mixture of alkene and syn-diolate from styrene oxide under conditions where diolate cycloreversion is a negligible contributor.

Kinetic isotope effects in cycloreversion of rhenium (V) diolates.

Cycloreversion of 4-methoxystyrene from the corresponding Tp'Re(O)(diolato) complex (Tp' = hydrido-tris-(3,5-dimethylpyrazolyl)borate) was measured competitively for various isotopomers at 103 degrees C. Primary ((12)C/(13)C) and secondary ((1)H/(2)H) kinetic isotope effects were determined. The primary KIEs were k(12C)/k(13C) = 1.041 +/- 0.005 at the alpha position and 1.013 +/- 0.006 at the beta position. Secondary KIEs were k(H)/k(D) = 1.076 +/- 0.005 at the alpha position and 1.017 +/- 0.005 at the beta position. Computational modeling (B3LYP/LACVP+) located a transition state for concerted cycloreversion of styrene from TpRe(O)(OCH(2)CHPh) exhibiting dramatically different C-O bond lengths. A Hammett study on cycloreversions of substituted styrenes from a series of Tp'Re(O)(diolato) showed dichotomous behavior for electron donors and electron-withdrawing groups as substituents: rho = -0.65 for electron donors, but rho = +1.13 for electron-withdrawing groups. The data are considered in light of various mechanistic proposals. While the extrusion of 4-methoxystyrene is concluded to be a highly asynchronous concerted reaction, the Hammett study reflects a likelihood that multiple reaction mechanisms are involved.