A simple method for extracting both active oily and water soluble extract (WSE) from Nigella sativa (L.) seeds using a single solvent system

The current study provides a way of extraction for both active NSO and WSE from Nigella sativa seeds using 98% methanol. About 1?kg of ground seeds was macerated by 1:2.5 w/v (g/mL) for 72?hours. After rotary evaporation and 7 days of continuous drying and chilling at 50 and 4?°C, NSO and WSE were obtained at the same instant. Solubility tests of 24 solvents and 11 thin layer chromatographic analyses while 2, 2-diphenyl-1-picrylhydrazyl free radical scavenging assay of NSO (73.66) , WSE (33.32) and NSO?+?WSE (78.22) against ascorbic acid (IC50?=?4.28?mg/mL) was performed. WSE was found to be highly soluble in water and 5% NaOH exhibiting the same Rf value of 0.95 for EtOH:DMSO (9:1) against the honey. WSE has revealed more than twofold higher anti-oxidant activity than others. Formulation of WSE with Tualang honey may provide better targeted hydrophilic drug delivery systems.     

Terminal Hydride Species in [FeFe]‐Hydrogenases Are Vibrationally Coupled to the Active Site Environment

A combination of nuclear resonance vibrational spectroscopy (NRVS), FTIR spectroscopy, and DFT calculations was used to observe and characterize Fe?H/D bending modes in CrHydA1 [FeFe]‐hydrogenase Cys‐to‐Ser variant C169S. Mutagenesis of cysteine to serine at position 169 changes the functional group adjacent to the H‐cluster from a ‐SH to ‐OH, thus altering the proton transfer pathway. The catalytic activity of C169S is significantly reduced compared to that of native CrHydA1, presumably owing to less efficient proton transfer to the H‐cluster. This mutation enabled effective capture of a hydride/deuteride intermediate and facilitated direct detection of the Fe?H/D normal modes. We observed a significant shift to higher frequency in an Fe?H bending mode of the C169S variant, as compared to previous findings with reconstituted native and oxadithiolate (ODT)‐substituted CrHydA1. On the basis of DFT calculations, we propose that this shift is caused by the stronger interaction of the ‐OH group of C169S with the bridgehead ‐NH‐ moiety of the active site, as compared to that of the ‐SH group of C169 in the native enzyme.     

High‐Frequency Fe–H Vibrations in a Bridging Hydride Complex Characterized by NRVS and DFT

High‐spin iron species with bridging hydrides have been detected in species trapped during nitrogenase catalysis, but there are few general methods of evaluating Fe?H bonds in high‐spin multinuclear iron systems. An ⁵⁷Fe nuclear resonance vibrational spectroscopy (NRVS) study on an Fe(μ‐H)₂Fe model complex reveals Fe?H stretching vibrations for bridging hydrides at frequencies greater than 1200 cm^?1. These isotope‐sensitive vibrational bands are not evident in infrared (IR) spectra, showing the power of NRVS for identifying hydrides in this high‐spin iron system. Complementary density functional theory (DFT) calculations elucidate the normal modes of the rhomboidal iron hydride core.     

Enantioselective Access to 1H‐Isoindoles with Quaternary Stereogenic Centers by Palladium(0)‐Catalyzed C−H Functionalization

A catalytic enantioselective method for the synthesis of chiral 1H‐isoindoles bearing quaternary stereogenic centers is reported. Powered by readily accessible phosphordiamidite ligands, the presented palladium(0)‐catalyzed C?H functionalization uses trifluoroacetimidoyl chlorides as electrophilic components. It delivers previously inaccessible perfluoroalkylated 1H‐isoindoles in high yields and enantioselectivities. The subsequent diastereoselective addition of nucleophiles provides access to densely substituted and sterically hindered isoindolines.     

Performance of SM8 on a test to predict small-molecule solvation free energies

The SM8 quantum mechanical aqueous continuum solvation model is applied to a 17-molecule test set proposed by Nicholls et al. (J. Med. Chem. 2008, 51, 769) to predict free energies of solvation. With the M06-2X density functional, the 6-31G(d) basis set, and CM4M charge model, the root-mean-square error (RMSE) of SM8 is 1.08 kcal mol(-1) for aqueous geometries and 1.14 kcal mol(-1) for gas-phase geometries. These errors compare favorably with optimal explicit and continuum models reported by Nicholls et al., having RMSEs of 1.33 and 1.87 kcal mol(-1), respectively. Other models examined by these workers had RMSEs of 1.5-2.6 kcal mol(-1). We also explore the use of other density functionals and charge models with SM8 and the RMSE increases to 1.21 kcal mol(-1) for mPW1/CM4 with gas-phase geometries, to 1.50 kcal mol(-1) for M06-2X/CM4 with gas-phase geometries, and to 1.27-1.64 kcal mol(-1) with three different models at B3LYP gas-phase geometries.     

Direct examination of H2O2 activation by a heme peroxidase

Described here is the application of oxygen isotope fractionation together with computational methods, to elucidate a mechanism of enzymatic H2O2 activation. Horseradish peroxidase (HRP) has been the subject of intensive experimental and computational studies, yet questions remain as to the reversibility of the O-O cleavage step. New insight is afforded by the competitive oxygen kinetic isotope effect (18O KIE) upon H2O2 consumption determined under turnover conditions. The 18O KIE is compared to isotope effects calculated for the O-O heterolysis transition state and potential intermediates using density functional theory. In addition, experiments in enriched water provide evidence for HRP-catalyzed scrambling of the 18O label into the unreacted H2O2. The results provide an unprecedented view of H2O2 activation by a heme peroxidase and challenge the assumption of rate-limiting O-O heterolysis.