Determination of 13C chemical shift anisotropy tensors and molecular order of 4-hexyloxybenzoic acid

4-Alkoxy benzoic acids belong to an important class of thermotropic liquid crystals that are structurally simple and often used as starting materials for many novel mesogens. 4-Hexyloxybenzoic acid (HBA) is a homologue of the same series and exhibits an enantiotropic nematic phase. As this molecule could serve as an ideal model compound, high resolution (13)C NMR studies of HBA in solution, solid, and liquid crystalline phases have been undertaken. In the solid state, two-dimensional separation of undistorted powder patterns by effortless recoupling (2D SUPER) experiments have been carried out to estimate the magnitude of the components of the chemical shift anisotropy (CSA) tensor of all the aromatic carbons. These values have been used subsequently for calculating the orientational order parameters in the liquid crystalline phase. The CSA values computed by density functional theory (DFT) calculations showed good agreement with the 2D SUPER values. Additionally, (13)C-(1)H dipolar couplings in the nematic phase have been determined by separated local field (SLF) spectroscopy at various temperatures and were used for computing the order parameters, which compared well with those calculated by using the chemical shifts. It is anticipated that the CSA values determined for HBA would be useful for the assignment of carbon chemical shifts and for the study of order and dynamics of structurally similar novel mesogens in their nematic phases.     

Screening and rank ordering of reversible mechanism‐based inhibitors of Hepatitis C virus NS3 protease using electrospray ionization mass spectrometry

An affinity‐selection study using size exclusion chromatography (SEC) combined with off‐line electrospray ionization mass spectrometry (ESI‐MS) was performed on libraries of peptidic α‐ketoamide inhibitors directed against the hepatitis C virus (HCV) NS3 protease. A limiting amount of HCV NS3 protease (25 µM ) was incubated with equimolar amounts (100 µM ) of 49 reversible mechanism‐based ketoamide inhibitors, previously grouped into seven sets to ensure clearly distinguishable mass differences of the enzyme‐inhibitor complexes (>10 Da). The unbound compounds were separated rapidly from the protease and the protease‐inhibitor complexes by SEC spin columns. The eluate of the SEC was immediately analyzed by direct‐infusion ESI‐MS. An enzyme‐inhibitor complex, with a molecular mass corresponding to the NS3 protease binding to the preferred inhibitor, SCH212986, was the only molecular species detected. By increasing the molar ratio of HCV NS3 protease to inhibitors to 1:2 while keeping the inhibitors' concentration constant, the complex of the second most tightly bound inhibitor, SCH215426, was also identified. Although the potencies of these inhibitors were virtually un‐measurable by kinetic assays, a rank order of CVS4441 > SCH212986 > SCH215426 was deduced for their inhibition potencies by direct competition experiment with CVS4441 ( M ). As discussed in the article, through judicious application of this strategy, even large libraries of fairly weak, reversible and slow‐binding inhibitors could be rapidly screened and rank ordered to provide critical initial structure‐activity insights. Copyright © 2011 John Wiley & Sons, Ltd.     

Anti-infective potential of caffeic acid and epicatechin 3-gallate isolated from methanol extract of Euphorbia hirta (L.) against Pseudomonas aeruginosa

Euphorbia hirta (L.) plant is traditionally used in Malaysia for the treatment of gastrointestinal, bronchial and respiratory ailments caused by nosocomial infectious agents. Bioactivity-guided fractionation of the methanol extract of the aerial parts of E. hirta and analysis using high-performance liquid chromatography have led to the isolation of two antibacterial compounds. These compounds were identified as caffeic acid (CA) and (–)-epicatechin 3-gallate (ECG) based on spectroscopic analyses and comparison with previously published data. Using broth microdilution method, both ECG and CA had demonstrated significant minimum inhibitory concentration of 15.6 and 31.3 μg/mL respectively, against Pseudomonas aeruginosa. Time-kill assessment of ECG and CA displayed bactericidal effect on P. aeruginosa cells.     

Targeting Antibiotic Resistance

Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.     

Dynamical and Mechanical Insights into the Li(2S)+ HCl( ) Reaction: A Detailed Quantum Wavepacket Study

Quantum wave packet dynamics of the Li(²S)+HCl( ) reaction in its electronic ground state is studied. The initial state-selected and energy-resolved dynamical attributes such as reaction probability, integral cross section, and thermal rate constant for the Cl-abstraction and H-abstraction pathways are reported. All partial wave contributions of J up to 120 were found to be necessary for the title reaction up to the collision energy of ∼1.0 eV. The dynamical results reveal that the Cl-abstraction is more favored over the H-abstraction for the different rovibrational (v, j) excitations. Due to the existence of an early barrier in the potential energy surface, the cross sections increase with increasing collision energy. The rate constants also monotonously increase with temperature for both channels. Resonances are identified and characterized in terms of eigenfunctions and lifetimes. Nearly 120 well-resolved eigenstates are reported for the LiHCl complex, and they are categorized as van der Waals (vdW), barrier and product states according to the nodal progressions along (R, r, γ). The vdW resonances reveal a local-mode behavior of quasibound type at low energies and extended progressions at high energies. Further, the single-quantized periodic orbit type is also observed in the barrier region, which decays very fast. Finally, the lifetime analysis reveals that the vdW resonances can survive as long as ∼2.2 ps, which is much longer than the lifetime of the resonances in the barrier region.