Methionine ligand lability of type I cytochromes c: detection of ligand loss using protein film voltammetry

Protein film voltammetry (PFV) is used to interrogate the behavior of a variety of bacterial and mitochondrial His/Met-ligated cytochromes c. While analogous studies upon alkanethiol-modified gold electrodes reveal the anticipated Fe(II/III) couple only, PFV using pyrolytic graphite edge (PGE) electrodes demonstrates the presence of a lower-potential form of each of the cyts c studied, with a potential of approximately -100 mV (vs hydrogen). The generation of the novel, lower-potential state is shown to arise specifically from the interaction with the PGE electrode. Simultaneously, the typical Fe(II/III) couple can be observed. PFV of a series of wild-type cytochromes and mutants in the Met-donating loop show that the lower-potential state is highly similar between proteins from Pseudomonas aeruginosa (PA), Hydrogenobacter thermophilus (HT), and horse heart. The generation of the lower-potential form correlates inversely with the stability of the Met-Fe interaction for each of the cytochromes. Comparison with chemically unfolded cyts c indicates that the lower-potential forms detected here are unique, and this distinct state is ascribed to the loss of the Met ligand. Thus, PGE is demonstrated to be a non-innocent electrode surface in PFV studies of His/Met-ligated cytochromes c.     

Substituted tertiary phosphine Ru(II) organometallics: catalytic utility on the hydrolysis of etofibrate in pharmaceuticals

Some new organometallics of ruthenium(II) of the type [RuCl(2)(COD)(CO)L] (1a-f) and [RuCl(2)(COD)L(2)] (2a-f) (where L is substituted tertiary phosphines), have been synthesized by using precursors [RuCl(2)(COD)(CO)(CH(3)CN)] (1) and [RuCl(2)(COD)(CH(3)CN)(2)] (2) with the substituted tertiary phosphine ligands in 1:1 and 1:2 molar ratio. The organometallics (2a-f) have been further reacted with carbonmonoxide to produce compounds of the type [RuCl(2)(CO)L(2)] (3a-f). These compounds were characterized by elemental analysis, IR, NMR ((1)H, (13)C and (31)P), mass and electronic spectral data. The catalytic activity of all these organometallics were studied and found that they are efficient catalysts for hydrolysis of etofibrate. The hydrolyzed product was separated by column chromatography and the percent yields are found in the range of 98.6-99.1%.     

Sulfonic acid functionalized silica as an efficient heterogeneous recyclable catalyst for one‐pot synthesis of 2‐substituted benziimidazoles

An efficient one‐pot synthesis of 2‐substituted benzimidazoles from o‐phenylenediamine and aldehydes in the presence of sulfonic acid functionalized silica at room temperature is reported.     

Reduction of tertiary phosphine oxides with DIBAL-H

The reduction of tertiary phosphine oxides (TPOs) and sulfides with diisobutylaluminum hydride (DIBAL-H) has been studied in detail. An extensive solvent screen has revealed that hindered aliphatic ethers, such as MTBE, are optimum for this reaction at ambient temperature. Many TPOs undergo considerable reduction at ambient temperature and then stall due to inhibition. 31P and 13C NMR studies using isotopically labeled substrates as well as competition studies have revealed that the source of this inhibition is tetraisobutyldialuminoxane (TIBAO), which builds up as the reaction proceeds. TIBAO selectively coordinates the TPO starting material, preventing further reduction. Several strategies have been found to circumvent this inhibition and obtain full conversion with this extremely inexpensive reducing agent for the first time. Practical reduction protocols for these critical targets have been developed.     

Predicted structures and dynamics for agonists and antagonists bound to serotonin 5-HT2B and 5-HT2C receptors

Subtype 2 serotonin (5-hydroxytryptamine, 5-HT) receptors are major drug targets for schizophrenia, feeding disorders, perception, depression, migraines, hypertension, anxiety, hallucinogens, and gastrointestinal dysfunctions. (1) We report here the predicted structure of 5-HT2B and 5-HT2C receptors bound to highly potent and selective 5-HT2B antagonist PRX-08066 3, (pKi: 30 nM), including the key binding residues [V103 (2.53), L132 (3.29), V190 (4.60), and L347 (6.58)] determining the selectivity of binding to 5-HT2B over 5-HT2A. We also report structures of the endogenous agonist (5-HT) and a HT2B selective antagonist 2 (1-methyl-1-1,6,7,8-tetrahydro-pyrrolo[2,3-g]quinoline-5-carboxylic acid pyridine-3-ylamide). We examine the dynamics for the agonist- and antagonist-bound HT2B receptors in explicit membrane and water finding dramatically different patterns of water migration into the NPxxY motif and the binding site that correlates with the stability of ionic locks in the D(E)RY region.     

Role of encapsulation of Na+ and F- ions on the Diels-Alder reactivity of C32

The density functional theory (DFT)-based Becke's three parameter hybrid exchange functional and Lee-Yang-Parr correlation functional (B3LYP) calculations have been performed to understand the role of encapsulation of Na(+) and F(-) ions on the Diels-Alder reactivity of C(32). In this context, C(32) has been taken as the dienophile and cis-1,3-butadiene has been considered as diene. Results obtained from the calculations on the Na(+)@C(32) and F(-)@C(32) have also been compared with that of C(32). It is found from the results that encapsulated Na(+) ion acts as a catalyst, whereas the encapsulated F(-) does not accelerate the reaction between C(32) and cis-1,3-butadiene. Thus, the reactivity of F(-)@C(32) is less than that of free C(32) and Na(+)@C(32). Formation of adduct involving [5,5]-B bond is preferred over other bonds. The energy decomposition analysis has been applied to understand the role of confinement on an encaged ion. The part played by the charge transfer interaction is evident from the NBO analysis. The frontier orbital analysis points out that the reaction is driven by the normal electron demand.     

Effect of gold electrode crystallographic orientations on charge transport through aromatic molecular junctions

ABSTRACT

We examined the electrical conduction through single-molecular junctions comprising of anthracenedithiol molecule coupled to two gold electrodes having ?1,0,1?, ?1,1,0? and ?1,1,1? crystallographic orientations. Owing to this jellium model, we evaluated the values of current and conductance using non-equilibrium Green's functions combined with extended Huckel theory. This data was further interpreted in terms of transmission spectra, density of states and their molecular orbital analysis for zero bias. We evinced the oscillating conductance in all three cases, due to the oscillation of orbital energy relative to Fermi level. Our detailed analysis suggested that electrode orientation can tune the molecule–electrode coupling and hence conduction. Anthracene molecular junction with ?1,1,0? orientation displayed favourable conduction, when compared to the other two orientations, thus can provide us an insight while designing futuristic molecular electronic devices.     

Amide bond synthesis via silver(I) N-heterocyclic carbene-catalyzed and tert-butyl hydroperoxide-mediated oxidative coupling of alcohols with amines under base free conditions

We present a base free method for amide bond construction via oxidative coupling of alcohols with amines catalyzed by Silver(I) N-heterocyclic carbenes (Ag(I)-NHCs) and mediated by tert-butyl hydroperoxide (TBHP) in ethanol. The results of controlled experiments suggest that the oxidative coupling proceeds through the formation of aldehyde, then subsequent attack by amine to give hemiaminal, which can then be oxidized to amide.