Asymmetric aerobic oxidation of alpha-hydroxy acid derivatives by C4-symmetric, vanadate-centered, tetrakisvanadyl(V) clusters derived from N-salicylidene-alpha-aminocarboxylates

A series of chiral vanadyl(V) methoxides bearing 3-t-butyl-5-substituted N-salicylene-L-valinate and L-t-leucinate as chiral auxiliaries has been prepared. In all cases except the 3,5-di-t-butyl analogue, they exist as monomers both in solution and in the single crystal state. In the case of the 3,5-di-t-butyl analogue, the architectural nature of the vanadyl(V) complex highly depends on the base used during the complex formation event. A pentanuclear C4-symmetric complex was formed when potassium salts were employed instead of the corresponding sodium salts. A central vanadate(V) unit serves to grip four identical chiral monomeric vanadyl(V) units together, by which a potassium ion sits on top of the four flanking units through carbonyl coordinations and serves to hold the whole cluster by cooperation with the central vanadate(V) unit. In comparison with the corresponding monomeric vanadyl(V) methoxide complex, the cluster complex was utilized to facilitate the asymmetric aerobic oxidations of various racemic alpha-hydroxyesters, -amides, and -thioesters with excellent selectivity factors (krel 40 to >500).     

Accurate and efficient corrections for missing dispersion interactions in molecular simulations

In simulations, molecular dispersion interactions are frequently neglected beyond a cutoff of around 1 nm. In some cases, analytical corrections appropriate for isotropic systems are applied to the pressure and/or the potential energy. Here, we show that in systems containing macromolecules, either of these approaches introduce statistically significant errors in some observed properties; for example, the choice of cutoff can affect computed free energies of ligand binding to proteins by 1 to 2 kcal/mol. We review current methods for eliminating this cutoff-dependent behavior of the dispersion energy and identify some situations where they fail. We introduce two new formalisms, appropriate for binding free energy calculations, which overcome these failings, requiring minimal computational effort beyond the time required to run the original simulation. When these cutoff approximations are applied, which can be done after all simulations are completed, results are consistent across simulations run with different cutoffs. In many situations, simulations can be run with even shorter cutoffs than typically used, resulting in increased computational efficiency.     

Fluorescence quenching of 3-methyl 7-hydroxyl Coumarin in presence of acetone

Fluorescence quenching of 3-methyl 7-hydroxyl Coumarin in prescence of the acetone is reported here. It was found that the quenching observed was of dynamic nature. It is also observed that quenching of the fluorescence of the indicator had a full reversiblity. As it has a full reversiblity, a novel optical sensor for acetone can be constructed on this quenching.     

Normal mode partitioning of Langevin dynamics for biomolecules

We propose a novel normal mode multiple time stepping Langevin dynamics integrator called NML. The aim is to approximate the kinetics or thermodynamics of a biomolecule by a reduced model based on a normal mode decomposition of the dynamical space. Our basis set uses the eigenvectors of a mass reweighted Hessian matrix calculated with a biomolecular force field. This particular choice has the advantage of an ordering according to the eigenvalues, which have a physical meaning of being the square of the mode frequency. Low frequency eigenvalues correspond to more collective motions, whereas the highest frequency eigenvalues are the limiting factor for the stability of the integrator. In NML, the higher frequency modes are overdamped and relaxed near their energy minimum while respecting the subspace of low frequency dynamical modes. Our numerical results confirm that both sampling and rates are conserved for an implicitly solvated alanine dipeptide model, with only 30% of the modes propagated, when compared to the full model. For implicitly solvated systems, NML gives a twofold improvement in efficiency over plain Langevin dynamics for sampling a small 22 atom (alanine dipeptide) model and in excess of an order of magnitude for sampling an 882 atom (bovine pancreatic trypsin inhibitor) model, with good scaling with system size subject to the number of modes propagated. NML has been implemented in the open source software PROTOMOL.     

A simple high-performance liquid chromatographic method for the estimation of boswellic acids from the market formulations containing Boswellia serrata extract

A simple, rapid, and reproducible reverse-phase high-performance liquid chromatographic method is developed for the estimation of boswellic acids, the active constituents in Boswellia serrata oleo-gum resin. The chromatographic separation is performed using a mobile phase consisting of acetonitrile-water (90:10, % v/v) adjusted to pH 4 with glacial acetic acid on a Kromasil 100 C18 analytical column with flow rate of 2.0 mL/min and detection at 260 nm. The elution times are 4.30 and 7.11 min for 11-keto beta-boswellic acid (11-KBA) and 3-acetyl 11-keto beta-boswellic acid (A-11-KBA), respectively. The calibration curve is linear in the 11.66-58.30 microg/mL and 6.50-32.50 microg/mL range for 11-KBA and A-11-KBA, respectively. The limits of detection are 2.33 microg/mL and 1.30 microg/mL for 11-KBA and A-11-KBA, respectively. The mean recoveries are 98.24% to 104.17% and 94.12% to 105.92% for 11-KBA and A-11-KBA, respectively. The inter- and intra-day variation coefficients are less than 5%. The present method is successfully applied for the estimation of boswellic acids from the market formulations containing Boswellia serrata extract.     

Simultaneous determination of sugars and picrosides in Picrorhiza species using ultrasonic extraction and high-performance liquid chromatography with evaporative light scattering detection

Sugars play a critical role in regulating overall cellular metabolism in high altitude growing plants. These plants are shown to have high levels of sugars to enhance their tolerance to abiotic stresses such as drought and freezing temperature. In the present study, a simple, sensitive, selective and reliable HPLC method based on ultrasonic extraction and evaporative light scattering detection (ELSD) has been developed and validated for the simultaneous determination of important sugars (xylose, xylitol, mannitol, glucose and sucrose) and picrosides (picroside-I and picroside-II) in two species Picrorhiza kurroa and P. scrophulariiflora. The analysis was carried out on a Zorbax amino column (250 mm x 4.6 mm i.d., 5 microm) with isocratic elution of acetonitrile:water (78:22, v/v). The method was validated for accuracy, precision, limit of detection and quantification according to International Conference on Harmonization (ICH) guidelines. The drift tube temperature of the ELSD system was set to 81 degrees C and nitrogen flow rate was 2.0 standard liter per minute (SLM). The regression equation revealed a good linear relationship (r(2)=0.9997+/-0.0012) within test ranges. The limit of detection and quantification for seven analytes in ELSD were less than 0.98 and 2.95 microg, respectively. The method showed good reproducibility for the quantification of seven analytes in Picrorhiza species with intra- and inter-day variation of less than 2.0%.     

Chemical denaturants inhibit the onset of dewetting

The mechanism by which the aqueous cosolvents guanidinium chloride and urea denature proteins is a matter of controversy. Here, we use all-atom molecular dynamics simulations to study the effect of both denaturants on the dewetting of water confined between nanoseparated hydrophobic plates. It is found that the denaturants inhibit the onset of dewetting, so that it occurs at shorter interplate distances than in pure water. Our results support a role for urea and guanidinium in assisting in the solvation of nonpolar surfaces, thereby weakening hydrophobic effects known to be important for protein stability.     

Structural insight into RNA hairpin folding intermediates

Hairpins are a ubiquitous secondary structure motif in RNA molecules. Despite their simple structure, there is some debate over whether they fold in a two-state or multi-state manner. We have studied the folding of a small tetraloop hairpin using a serial version of replica exchange molecular dynamics on a distributed computing environment. On the basis of these simulations, we have identified a number of intermediates that are consistent with experimental results. We also find that folding is not simply the reverse of high-temperature unfolding and suggest that this may be a general feature of biomolecular folding.     

Quaternary ammonium salt-based chromogenic and fluorescent chemosensors for fluoride ions

Chemosensors 5-7 possessing a quaternary ammonium cation (for electrostatic interactions) and an N-H group(s) (for H-bonding) as recognition sites and an anthracene-9,10-dione as both a chromogenic and fluorescent moiety exhibit absorption and emission changes with fluoride ions only. No significant response to other anions such as Cl⁻, Br⁻, I⁻, , CH₃COO⁻, , and is observed. The dual emission at λ_max 580 nm (free 5/6) and λ_max 510 and 540 nm (5/6 + F⁻) in chemosensors 5 and 6 enables ratiometric analysis of fluoride ions.     

Increasing the Value of Hominy Feed as a Coproduct by Fermentation

Hominy feed is a low value ($83.7/metric ton) coproduct of the corn dry milling process that accounts for nearly 35% of the starting corn quantity. The average composition of hominy feed on a dry basis is 56.9% starch, 25.2% neutral detergent fiber, 11.1% protein, and 5.3% fat. Starch in hominy feed can be fermented to ethanol thus increasing its levels of protein and fat. The increase in protein and fat percentages may increase the market competitiveness and price of hominy feed. Hydrolysis and fermentation were performed on nine hominy feed samples collected from three corn dry milling plants in the USA. The original hominy feed samples and postfermentation solids were analyzed for starch, protein, fat, and fiber content. Compared to the original hominy feed, the percentage increase in protein, fat and fiber in postfermentation solids of nine samples ranged from 10.4 to 21.3, 6.78 to 10.6, and 12.6 to 28.7% (dry basis), respectively. Ethanol yields varied from 271.7 to 380.2 l/metric ton for the nine hominy feed samples. These results indicate that the value of hominy feed as an animal feedstock can potentially be increased with fermentation and can produce more profit per metric ton than currently being derived by its sale as a low protein feed ingredient.