Possible DNA damage by oxidation products of guanine: A density functional and electron propagator theoretical study

The stability and reactivity of seven guanine oxidation products (GOP), which contain 8‐oxo‐7,8‐dihydroguanine (8‐oxoG) have been studied and compared with the four nucleobases, such as adenine, cytosine, guanine, and thymine. It has been possible with the use of density functional theory and electron propagator theory (EPT), to evaluate their relation with certain ionization induced process, which produce damage to DNA. Using the application of Koopmans's theorem, EPT provides alternatively a reliable way to calculate the vertical ionization potential (VIP) and vertical electron affinity (VEA). This process has been used to obtain other reactivity indexes, such as: electronegativity and hardness. In the nucleobases and the GOP studies, we observed the following: guanine and 8‐oxo‐7,8‐dihydroguanine were the lowest VIP, and 8‐oxoG was the lowest hardness. This let us confirm that these species are the most susceptible to change their electron densities and transform in other GOP. Particularly, the GOP, Sp(R), Sp(S), and Z were the highest VIP. It allows us to say that they are the most stable. Z and Iz were the highest VEA; this suggests that they have a big capacity to accept electrons and form anionic centers in DNA. The GOP, which was considered in this study, showed hardness values between 9.1 and 10.4 because of π‐conjugation; therefore, these GOP could be good candidates to participate in DNA transversions. © 2012 Wiley Periodicals, Inc.     

Novel small-molecule inhibitors of arylamine N-acetyltransferases: drug discovery by high-throughput screening

Arylamine N-acetyltransferases (NATs) are a family of enzymes found in eukaryotes and prokaryotes. While the precise endogenous function of NAT remains unknown for most organisms, recent evidence has shown that the expression of human NAT1 is up-regulated in estrogen receptor positive breast cancer. Additionally, NAT in mycobacteria is required for mycobacterial cell wall biosynthesis and survival of the organisms within macrophage. It is therefore important to develop small molecule inhibitors of NATs as molecular tools to study the function of NATs in various organisms. Such inhibitors may also prove useful in future drug design, for example in the development of anti tubercular agents. We describe a high-throughput screen of a proprietary library of 5016 drug-like compounds against three prokaryotic NAT enzymes and two eukaryotic NAT enzymes.     

The Algorithm Z and Ramanujan’s <Subscript>1</Subscript><Emphasis Type="Italic">ψ</Emphasis><Subscript>1</Subscript> summation

We use the Algorithm Z on partitions due to Zeilberger, in a variant form, to give a combinatorial proof of Ramanujan’s ₁ ψ ₁ summation formula.     

Substituent and solvent effects on the beta-heterolysis reaction of beta-hydroxy arylethyl radicals

Time-resolved conversion of a series of beta-hydroxy arylethyl radicals with electron-donating and -withdrawing aromatic substituents to their corresponding styrene radical cation via heterolytic loss of the beta-hydroxy leaving group was examined with nanosecond laser flash photolysis. In all cases, the reaction was catalyzed by added perchloric acid. Radicals 2a-d reacted via a pre-equilibrium protonation mechanism in acidic 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), and measuring rate constants for radical cation formation as a function of acid content allowed for the determination of absolute rate constants ranging from 3.6 x 10(6) to 3.8 x 10(7) s(-1) for the loss of water from the protonated beta-hydroxy arylethyl radicals 2a-d, as well as the acidity constants, pKa approximately 1.5 (in HFIP), for the protonated radicals. The 4-methoxy-substituted beta-hydroxy arylethyl radical 2e reacted by rate determining protonation in HFIP with a second-order rate constant of k(H+) = 7.8 x 10(8) M(-1) s(-1). However, in acetonitrile, 2,2,2-trifluoroethanol, and mixtures of these two solvents, 2e reacted by pre-equilibrium protonation, allowing for solvent effects on the rate constant for loss of water from the protonated radical 2e to be determined. With use of these data, substituent electronic effects on the kinetics of the beta-heterolysis reaction are discussed. Differences in the effect of solvent on the rate constant for loss of water from the protonated beta-hydroxy arylethyl radicals and other beta-substituted arylethyl radicals are also discussed.     

Isolation,characterization, and determination of a new compound in red wine

Chromatographic separation using fluorescence as a detection mode revealed, besides a series of flavan-3-ols, the recurrent presence of an undefined compound in Bordeaux red wine. Its isolation and structure characterization by complementary means (high-resolution mass spectrometry, nuclear magnetic resonance, and chemical synthesis) has permitted us to identify it as the nitrogen-containing glycoconjugate 3-indolyl-(2R)-O-β-d-glucosyl-lactic acid. Its quantification was performed for different wines of different vine varieties and terroirs with the aim to assess whether this compound may be used as a terroir, variety, or wine process tag.     

An Enzyme Cascade Synthesis of ε‐Caprolactone and its Oligomers

Poly‐ε‐caprolactone (PCL) is chemically produced on an industrial scale in spite of the need for hazardous peracetic acid as an oxidation reagent. Although Baeyer–Villiger monooxygenases (BVMO) in principle enable the enzymatic synthesis of ε‐caprolactone (ε‐CL) directly from cyclohexanone with molecular oxygen, current systems suffer from low productivity and are subject to substrate and product inhibition. The major limitations for such a biocatalytic route to produce this bulk chemical were overcome by combining an alcohol dehydrogenase with a BVMO to enable the efficient oxidation of cyclohexanol to ε‐CL. Key to success was a subsequent direct ring‐opening oligomerization of in situ formed ε‐CL in the aqueous phase by using lipase A from Candida antarctica, thus efficiently solving the product inhibition problem and leading to the formation of oligo‐ε‐CL at more than 20 g L ^?1 when starting from 200 mM cyclohexanol. This oligomer is easily chemically polymerized to PCL.     

Taming the Carboxyl Group for Directed Carbometalation: Observations on the Use of Anions,Dianions and Ester Enolates

Carboxylate anions, dianions and ester enolates provide simultaneous protection and activation for directed carbometalation reactions. Advantage can be taken of the bis‐carbanionic character of the intermediate for further controlled C?C bond forming reactions.