Inter-DNA attraction mediated by divalent counterions

Can nonspecifically bound divalent counterions induce attraction between DNA strands? Here, we present experimental evidence demonstrating attraction between short DNA strands mediated by Mg2+ ions. Solution small angle x-ray scattering data collected as a function of DNA concentration enable model independent extraction of the second virial coefficient. As the [Mg2+] increases, this coefficient turns from positive to negative reflecting the transition from repulsive to attractive inter-DNA interaction. This surprising observation is corroborated by independent light scattering experiments. The dependence of the observed attraction on experimental parameters including DNA length provides valuable clues to its origin.     

Palladium-catalyzed [3+2] cycloaddition of carbon dioxide and trimethylenemethane under mild conditions

Carbon dioxide undergoes a Pd-catalyzed [3+2] cycloaddition with trimethylenemethane (TMM) under mild conditions (1 atm, 75 degrees C, 30 min) to produce a gamma-butyrolactone product in 63% yield, when the Pd-TMM complex is generated from 2-(acetoxymethyl)-3-(trimethylsilyl)propene. The reaction reported here is more rapid than the all-carbon [3+2] cycloaddition, and only the gamma-butyrolactone is produced in a competition experiment. With substituted substrates, the reaction is completely regioselective, producing the product derived from the kinetic Pd-TMM complex.     

An enantioselective route to alpha-methyl carboxylic acids via metal and enzyme catalysis

Dynamic kinetic resolution of allylic alcohols to allylic acetates followed by copper-catalyzed allylic substitution gave alkenes in high yields and high optical purity. Subsequent oxidative C-C double bond cleavage afforded pharmaceutically important alpha-methyl substituted carboxylic acids in high ee.     

Carboxyketenes, methyleneketenes, vinylketenes, oxetanediones, ynols, and ylidic ketenes from Meldrum's acid derivatives

It has been documented that 5-methylene-Meldrum's acid derivatives (1, 12 ) and their enols (2, 13) can undergo fragmentation to malonic anhydrides (4, 19 ), carboxyketenes (3, 16) and methyleneketene (5, 21 , 35 ), as well as cyclization to pyrrole-3-one and thiophene-3-one derivatives 11a,b (but not furan-3-ones 11c ) under the conditions of flash vacuum thermolysis (FVT). Here we report theoretical calculations at the B3LYP/6-311 + G(2d, p) and G3X(MP2) levels of theory, which allow a rationalization of these observations. The calculated activation barriers for these reactions are all of the order of 37-40 kcal mol(-1). Hydroxyacetylenes (alkynols) 7 are sometimes observed in FVT reactions of Meldrum's acid derivatives. Their formation is now explained as an FVT reaction of the carboxyketenes (e.g. 3-->7 and 32-->34) with a calculated activation barrier of ca. 39 kcal mol(-1). The cyclization of alkylamino- and alkylthio-substituted methyleneketenes 8a,b to pyrrolone and thiophenone derivatives 11a,b is found to be energetically very feasible under FVT conditions, and even in some cases in solution, with activation barriers of 33-39 kcal mol(-1). This cyclization takes place via the fleeting ylidic ketene intermediates 9a,b,25, and 37a,b, which exist in very shallow energy minima. Alkoxy-substituted methyleneketenes 8c do not cyclize in this manner due to the rather high, but in principle not impossible, activation barriers for the initial 1,4-H shifts to the ylidic ketenes 9c (ca. 47 kcal mol(-1)).     

A cadmium hydroxide complex of a N3S-donor ligand containing two hydrogen bond donors: synthesis, characterization, and CO2 reactivity

Treatment of the ebnpa (N-2-(ethylthio)ethyl-N,N-bis((6-neopentylamino-2-pyridyl)methyl)amine) ligand with a molar equivalent amount of Cd(ClO(4))(2).5H(2)O in CH(3)CN followed by the addition of [Me(4)N]OH.5H(2)O yielded the cadmium hydroxide complex [(ebnpaCd)(2)(mu-OH)(2)](ClO(4))(2) (1). Complex 1 has a binuclear cation in the solid-state with secondary hydrogen-bonding and CH/pi interactions involving the ebnpa ligand. In acetonitrile, 1 forms a binuclear/mononuclear equilibrium mixture. The formation of a mononuclear species has been confirmed by conductance measurements of 1 at low concentrations. Variable temperature studies of the binuclear/mononuclear equilibrium provided the standard enthalpy and entropy associated with the formation of the monomer as DeltaH degrees = +31(2) kJ mol(-1) and DeltaS degrees = +108(8) J mol(-1) K(-1), respectively. Enhanced secondary hydrogen-bonding interactions involving the terminal Cd-OH moiety may help to stabilize the mononuclear complex. Treatment of 1 with CO(2) in acetonitrile results in the formation of a binuclear cadmium carbonate complex, [(ebnpaCd)(2)(mu-CO(3))](ClO(4))(2) (2).     

Gold(I)-isocyanide and gold(I)-carbene complexes as substrates for the laser decoration of gold onto ceramic surfaces

Gold-isocyanide complexes XAu(RNC) (X = halide, pseudohalide, R = alkyl, aryl) and water soluble gold-carbene complexes XAuC(NHPh)[MeN(CH(2)CH(2)O)(n)Me] (X = Cl, n = 1-11) have been prepared and evaluated as substrates for the direct laser writing of gold decoration onto ceramics.     

Dehydration versus deamination of N-terminal glutamine in collision-induced dissociation of protonated peptides

Some of the most prominent "neutral losses" in peptide ion fragmentation are the loss of ammonia and water from N-terminal glutamine. These processes are studied by electrospray ionization mass spectrometry in singly- and doubly-protonated peptide ions undergoing collision-induced dissociation in a triple quadrupole and in an ion trap instrument. For this study, four sets of peptides were synthesized: (1) QLLLPLLLK and similar peptides with K replaced by R, H, or L, and Q replaced by a number of amino acids, (2) QLnK (n = 0, 1, 3, 5, 7, 9, 11), (3) QLnR (n = 0, 1, 3, 5, 7, 9), and (4) QLn (n = 1, 2, 3, 4, 8). The results for QLLLPLLLK and QLLLPLLLR show that the singly protonated ions undergo loss of ammonia and to a smaller extent loss of water, whereas the doubly protonated ions undergo predominant loss of water. The fast fragmentation next to P (forming the y5 ion) occurs to a larger extent than the neutral losses from the singly protonated ions but much less than the water loss from the doubly protonated ions. The results from these and other peptides show that, in general, when N-terminal glutamine peptides have no "mobile protons", that is, the number of charges on the peptide is no greater than the number of basic amino acids (K, R, H), deamination is the predominant neutral loss fragmentation, but when mobile protons are present the predominant process is the loss of water. Both of these processes are faster than backbone fragmentation at the proline. These results are rationalized on the basis of resonance stabilization of the two types of five-membered ring products that would be formed in the neutral loss processes; the singly protonated ion yields the more stable neutral pyrrolidinone ring whereas the doubly protonated ion yields the protonated aminopyrroline ring (see Schemes). The generality of these trends is confirmed by analyzing an MS/MS spectra library of peptides derived from tryptic digests of yeast. In the absence of mobile protons, glutamine deamination is the most rapid neutral loss process. For peptides with mobile protons, dehydration from glutamine is far more rapid than from any other amino acid. Most strikingly, end terminal glutamine is by far the most labile source of neutral loss in excess-proton peptides, but not highly exceptional when mobile protons are not available. In addition, rates of deamination are faster in lysine versus arginine C-terminus peptides and 20 times faster in positively charged than negatively charged peptides, demonstrating that these formal neutral loss reactions are not "neutral reactions" but depend on charge state and stability.     

Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities

High-mobility group box 1 protein (HMGB1) is a nuclear component, but extracellularly it serves as a signaling molecule involved in acute and chronic inflammation, for example in sepsis and arthritis. The identification of HMGB1 inhibitors is therefore of significant experimental and clinical interest. We show that glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, inhibits HMGB1 chemoattractant and mitogenic activities, and has a weak inhibitory effect on its intranuclear DNA-binding function. NMR and fluorescence studies indicate that glycyrrhizin binds directly to HMGB1 (K(d) approximately 150 microM), interacting with two shallow concave surfaces formed by the two arms of both HMG boxes. Our results explain in part the anti-inflammatory properties of glycyrrhizin, and might direct the design of new derivatives with improved HMGB1-binding properties.