Reversible catalytic dehydrogenation of alcohols for energy storage.

Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this report, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. This reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels.

An Uncanny Dehydrogenation Mechanism: Polar Bond Control over Stepwise or Concerted Transition States.

The mechanism of the dehydrogenation of N-heterocycles with the recently established bifunctional catalyst (iPrPNP)Fe(CO)(H) was investigated through experiments and density functional theory calculations (iPrPNP = iPr2PCH2CH2NCH2CH2PiPr2). In this system, the saturated N-heterocyclic substrates are completely dehydrogenated to the aromatic products. Calculations indicate that dehydrogenation barriers of the C-C bonds are very high in energy (ΔG‡ = 37.4-42.2 kcal/mol), and thus dehydrogenation only occurs at the C-N bond (ΔG‡ = 9.6-22.2 kcal/mol). Interestingly, substrates like piperidine with relatively unpolarized C-N bonds are dehydrogenated through a concerted proton/hydride transfer bifunctional transition state involving the nitrogen on the PNP ligand. However, substrates with polarized C-N bonds entail stepwise (proton then hydride) bifunctional dehydrogenation.

Nickel and iron pincer complexes as catalysts for the reduction of carbonyl compounds.

The reductions of aldehydes, ketones, and esters to alcohols are important processes for the synthesis of chemicals that are vital to our daily life, and the reduction of CO2 to methanol is expected to provide key technology for carbon management and energy storage in our future. Catalysts that affect the reduction of carbonyl compounds often contain ruthenium, osmium, or other precious metals. The high and fluctuating price, and the limited availability of these metals, calls for efforts to develop catalysts based on more abundant and less expensive first-row transition metals, such as nickel and iron. The challenge, however, is to identify ligand systems that can increase the thermal stability of the catalysts, enhance their reactivity, and bypass the one-electron pathways that are commonly observed for first-row transition metal complexes. Although many other strategies exist, this Account describes how we have utilized pincer ligands along with other ancillary ligands to accomplish these goals. The bis(phosphinite)-based pincer ligands (also known as POCOP-pincer ligands) create well-defined nickel hydride complexes as efficient catalysts for the hydrosilylation of aldehydes and ketones and the hydroboration of CO2 to methanol derivatives. The hydride ligands in these complexes are substantially nucleophilic, largely due to the enhancement by the strongly trans-influencing aryl groups. Under the same principle, the pincer-ligated nickel cyanomethyl complexes exhibit remarkably high activity (turnover numbers up to 82,000) for catalytically activating acetonitrile and the addition of H-CH2CN across the C═O bonds of aldehydes without requiring a base additive. Cyclometalation of bis(phosphinite)-based pincer ligands with low-valent iron species "Fe(PR3)4" results in diamagnetic Fe(II) hydride complexes, which are active catalysts for the hydrosilylation of aldehydes and ketones. Mechanistic investigation suggests that the hydride ligand is not delivered to the carbonyl substrates but is important to facilitate ligand dissociation prior to substrate activation. In the presence of CO, the amine-bis(phosphine)-based pincer ligands are also able to stabilize low-spin Fe(II) species. Iron dihydride complexes supported by these ligands are bifunctional as both the FeH and NH moieties participate in the reduction of C═O bonds. These iron pincer complexes are among the first iron-based catalysts for the hydrogenation of esters, including fatty acid methyl esters, which find broad applications in industry. Our studies demonstrate that pincer ligands are promising candidates for promoting the first-row transition metal-catalyzed reduction of carbonyl compounds with high efficiency. Further efforts in this research area are likely to lead to more efficient and practical catalysts.

A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence.

Antibacterial drug development suffers from a paucity of targets whose inhibition kills replicating and nonreplicating bacteria. The latter include phenotypically dormant cells, known as persisters, which are tolerant to many antibiotics and often contribute to failure in the treatment of chronic infections. This is nowhere more apparent than in tuberculosis caused by Mycobacterium tuberculosis, a pathogen that tolerates many antibiotics once it ceases to replicate. We developed a strategy to identify proteins that Mycobacterium tuberculosis requires to both grow and persist and whose inhibition has the potential to prevent drug tolerance and persister formation. This strategy is based on a tunable dual-control genetic switch that provides a regulatory range spanning three orders of magnitude, quickly depletes proteins in both replicating and nonreplicating mycobacteria, and exhibits increased robustness to phenotypic reversion. Using this switch, we demonstrated that depletion of the nicotinamide adenine dinucleotide synthetase (NadE) rapidly killed Mycobacterium tuberculosis under conditions of standard growth and nonreplicative persistence induced by oxygen and nutrient limitation as well as during the acute and chronic phases of infection in mice. These findings establish the dual-control switch as a robust tool with which to probe the essentiality of Mycobacterium tuberculosis proteins under different conditions, including those that induce antibiotic tolerance, and NadE as a target with the potential to shorten current tuberculosis chemotherapies.

Highly Selective Formation of n-Butanol from Ethanol through the Guerbet Process: A Tandem Catalytic Approach.

A highly selective (>99%) tandem catalytic system for the conversion of ethanol (up to 37%) to n-butanol, through the Guerbet process, has been developed using a bifunctional iridium catalyst coupled with bulky nickel or copper hydroxides. These sterically crowded nickel and copper hydroxides catalyze the key aldol coupling reaction of acetaldehyde to exclusively yield the C4 coupling product, crotonaldehyde. Iridium-mediated dehydrogenation of ethanol to acetaldehyde has led to the development of an ethanol-to-butanol process operated at a lower temperature.

MRI characterization of temporal lobe epilepsy using rapidly measurable spatial indices with hemisphere asymmetries and gender features.

INTRODUCTION: The paucity of morphometric markers for hemispheric asymmetries and gender variations in hippocampi and amygdalae in temporal lobe epilepsy (TLE) calls for better characterization of TLE by finding more useful prognostic MRI parameter(s). METHODS: T1-weighted MRI (3 T) morphometry using multiple parameters of hippocampus-parahippocampus (angular and linear measures, volumetry) and amygdalae (volumetry) including their hemispheric asymmetry indices (AI) were evaluated in both genders. The cutoff values of parameters were statistically estimated from measurements of healthy subjects to characterize TLE (57 patients, 55% male) alterations. RESULTS: TLE had differential categories with hippocampal atrophy, parahippocampal angle (PHA) acuteness, and several other parametric changes. Bilateral TLE categories were much more prevalent compared to unilateral TLE categories. Female patients were considerably more disposed to bilateral TLE categories than male patients. Male patients displayed diverse categories of unilateral abnormalities. Few patients (both genders) had combined bilateral appearances of hippocampal atrophy, amygdala atrophy, PHA acuteness, and increase in hippocampal angle (HA) where medial distance ratio (MDR) varied among genders. TLE had gender-specific and hemispheric dominant alterations in AI of parameters. Maximum magnitude of parametric changes in TLE includes (a) AI increase in HA of both genders, (b) HA increase (bilateral) in female patients, and (c) increase in ratio of amygdale/hippocampal volume (unilateral, right hemispheric), and AI decrease in MDR, in male patients. CONCLUSION: Multiparametric MRI studies of hippocampus and amygdalae, including their hemispheric asymmetry, underscore better characterization of TLE. Rapidly measurable single-slice parameters (HA, PHA, MDR) can readily delineate TLE in a time-constrained clinical setting, which contrasts with customary three-dimensional hippocampal volumetry that requires many slice computation.

Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights.

The metabolic instability of an antitubercular small molecule CD117 was addressed through iterative alteration of a key sulfide substituent and interrogation of the effect on growth inhibition of cultured Mycobacterium tuberculosis. This process was informed by studies of the intramycobacterial metabolism of CD117 and its inactive carboxylic acid derivative. Isoxazole 4e and thiazole 4m demonstrated significant gains in mouse liver microsomal stability with slight losses in whole-cell activity. This work illustrates the challenges of antitubercular hit evolution, requiring a balance of chemical and biological insights.

A molecular iron catalyst for the acceptorless dehydrogenation and hydrogenation of N-heterocycles.

A well-defined iron complex (3) supported by a bis(phosphino)amine pincer ligand efficiently catalyzes both acceptorless dehydrogenation and hydrogenation of N-heterocycles. The products from these reactions are isolated in good yields. Complex 3, the active catalytic species in the dehydrogenation reaction, is independently synthesized and characterized, and its structure is confirmed by X-ray crystallography. A trans-dihydride intermediate (4) is proposed to be involved in the hydrogenation reaction, and its existence is verified by NMR and trapping experiments.

Iron-based catalysts for the hydrogenation of esters to alcohols.

Hydrogenation of esters is vital to the chemical industry for the production of alcohols, especially fatty alcohols that find broad applications in consumer products. Current technologies for ester hydrogenation rely on either heterogeneous catalysts operating under extreme temperatures and pressures or homogeneous catalysts containing precious metals such as ruthenium and osmium. Here, we report the hydrogenation of esters under relatively mild conditions by employing an iron-based catalyst bearing a PNP-pincer ligand. This catalytic system is also effective for the conversion of coconut oil derived fatty acid methyl esters to detergent alcohols without adding any solvent.

Ultrasonography as a useful modality for documenting sacroiliitis in radiographically negative inflammatory back pain: a comparative evaluation with MRI.

OBJECTIVES: The aims of this study were to identify and characterize features of sacroiliitis in patients with non-radiographic inflammatory low back pain by ultrasonography (USG) and to correlate the findings with that of MRI. METHODS: MRI and USG of SI joints were performed on 29 patients who fulfilled the definition of inflammatory low back pain according to the Assessment of SpondyloArthritis International Society 2009 criteria for axial SpA but were X-ray negative for sacroiliitis. Increased vascularity, low resistive index (RI) and hyperechogenicity of the joint space were considered USG features of sacroiliitis. The findings were compared with those of 32 controls. USG features of sacroiliitis were compared with MRI by κ statistics. RESULTS: Receiver operating characteristic analysis revealed cut-off values for flow signals and RI of 3 and 0.605, respectively. There was a significant difference in the number of flow signals, RI and echogenicity of the SI joint between MRI-proven cases and controls. The Cohen's κ for flow signals, RI and hyperechogenicity when compared with MRI were 0.816 (95% CI 0.676, 0.937) and 0.821 (95% CI 0.662, 0.965) and 0.403 (95% CI 0.108, 0.695). Taking both flow signals and RI parameters as criteria for determining sacroiliitis, comparison with MRI returned a κ of 0.816 (95% CI 0.601, 0.963). CONCLUSION: Three or more flow signals and a RI ≤0.605 can be applied as USG criteria for sacroiliitis. USG can be a cost-effective and non-inferior modality compared with MRI in documenting sacroiliitis in early SpA.

Role of multiparametric MRI in predicting muscle invasiveness in urinary bladder neoplasms with pathological correlations.

Urinary bladder cancer (BC) is one of the most frequent malignancies and the ninth most common malignancy worldwide. The objective of this study is to assess the role of multiparametric magnetic resonance imaging (mp-MRI) in predicting the invasiveness of urinary bladder space occupying lesions. Thirty-five patients diagnosed with bladder masses underwent an mp-MRI study. The results of three image sets were analysed and compared with the histopathological results as a reference standard: T2-weighted image (T2WI) plus dynamic contrast-enhanced (DCE), T2WI plus diffusion-weighted images (DWI), and mp-MRI, including T2WI plus DWI and DCE. The diagnostic accuracy of mp-MRI was evaluated using receiver operating characteristic curve analysis. We discovered a highly significant correlation between muscle invasiveness as staged by HPE (Histopathological examination) and mp-MRI utilising a VI-RADS score >3 (p 0.001) with a sensitivity of 100% and a specificity of 85.7%. With a diagnostic accuracy of 77.14%, a sensitivity of 92.31%, a specificity of 72.72%, a positive predictive value of 66.67%, and a negative predictive value of 94.11%, In terms of muscle invasiveness, there is good concordance between HPE staging and mp-MRI utilising the VI-RADS score. The mean apparent diffusion coefficient (ADC) values were higher in low grades than in high grades. The ROC curve study revealed a very strong correlation between HPE grade and ADC (p = 0.045). In 77.14% of patients, Mp-MRI correctly identified the local T stage. Mp-MRI is imaging biomarker for invasiveness and grade of tumour. The tumours with high grade are more invasive. However, the diagnostic accuracy of mp-MRI in determining muscle invasiveness is not very high and it overstages the disease in some cases (33.3%). Its clinical usefulness in determining muscle invasiveness before TURBT and histopathological examination can be questioned.

Pincer-ligated nickel hydridoborate complexes: the dormant species in catalytic reduction of carbon dioxide with boranes.

Nickel pincer complexes of the type [2,6-(R(2)PO)(2)C(6)H(3)]NiH (R = (t)Bu, 1a; R = (i)Pr, 1b; R = (c)Pe, 1c) react with BH(3)·THF to produce borohydride complexes [2,6-(R(2)PO)(2)C(6)H(3)]Ni(η(2)-BH(4)) (2a-c), as confirmed by NMR and IR spectroscopy, X-ray crystallography, and elemental analysis. The reactions are irreversible at room temperature but reversible at 60 °C. Compound 1a exchanges its hydrogen on the nickel with the borane hydrogen of 9-BBN or HBcat, but does not form any observable adduct. The less bulky hydride complexes 1b and 1c, however, yield nickel dihydridoborate complexes reversibly at room temperature when mixed with 9-BBN and HBcat. The dihydridoborate ligand in these complexes adopts an η(2)-coordination mode, as suggested by IR spectroscopy and X-ray crystallography. Under the catalytic influence of 1a-c, reduction of CO(2) leads to the methoxide level when 9-BBN or HBcat is employed as the reducing agent. The best catalyst, 1a, involves bulky substituents on the phosphorus donor atoms. Catalytic reactions involving 1b and 1c are less efficient because of the formation of dihydridoborate complexes as the dormant species as well as partial decomposition of the catalysts by the boranes.

A robust nickel catalyst for cyanomethylation of aldehydes: activation of acetonitrile under base-free conditions.

Nick of time: The nickel cyanomethyl complex 1 catalyzes the room temperature coupling of aldehydes with acetonitrile under base-free conditions. The catalytic system is long-lived and remarkably efficient with high turnover numbers (TONs) and turnover frequencies (TOFs) achieved. The mild reaction conditions allow a wide variety of aldehydes, including base-sensitive ones, to catalytically react with acetonitrile.

Evaluation of renal space occupying lesions with multiparametric MRI and its correlation with histopathology findings- an observational study.

The term multiparametric MRI, is a useful tool in reference to an approach that takes advantage of the added value of different MR imaging acquisitions to yield anatomic and pathophysiologic information about renal space occupying lesions and to evaluate patients with different tumors, including genitourinary malignancies. The role of multiparametric MRI is continuously growing because of its ability to detect and characterize renal space occupying lesions as well as to assess response to treatment. An observational study was carried out in 50 patients who presented with renal mass, based on clinical suspicion and prior imaging diagnosis of neoplastic renal space occupying lesion. Total renal space occupying lesions were 50, of which, 38 were males & 12 were females. The age range of the study population was 30-80 years. In our study, Agreement analysis between mpMRI diagnosis and HPE diagnosis of different RCC subtypes was statistically significant. So, multiparametric MRI had a role in differentiating the subtypes of RCC which had fair agreement with HPE. The present study results state that the renal mass lesions has different ADC values for different lesions because of the change in tissue contents and there was a statistically significant difference in ADC values between low and high-stage RCCs. Histologic and radiologic profiles of renal space occupying lesions and diverse subtypes of RCC can be used as biologic indicators of clinical behavior, response to treatment, and prognosis.

Design and evaluation of in situ gel eye drops containing nanoparticles of Gemifloxacin Mesylate.

Traditional eye drops used for topically administering drugs have poor ocular bioavailability due to the biological barriers of the eye. There is an interest to design and develop novel drug delivery systems that would extend the precorneal residence time, reduce the frequency of administration and decrease dose-related toxicity. This study aimed to prepare Nanoparticles of Gemifloxacin Mesylate and incorporate them into an in situ gel. The nanoparticles were prepared by ionic gelation technique, using 32 factorial design. Sodium tripolyphosphate (STPP) was used to crosslink Chitosan. The optimized formulation of the nanoparticles (GF4) contained 0.15% Gemifloxacin Mesylate, 0.15% Chitosan and 0.20% STPP, producing 71 nm particle size and 81.11% entrapment efficiency. The prepared nanoparticles showed biphasic release, with an initial burst release of 15% in 1.0 hr and a cumulative drug release of 90.53% at the end of 24 hrs. After that, the prepared nanoparticles were incorporated into an in situ gel, using Poloxamer 407, producing a sustained drug release with efficient antimicrobial activity against gram-positive and gram-negative bacteria as confirmed by the cup plate method.

Solid-state nuclear magnetic resonance studies delineate the role of the protein in activation of both aromatic rings of thiamin.

Knowledge of the state of ionization and tautomerization of heteroaromatic cofactors when enzyme-bound is essential for formulating a detailed stepwise mechanism via proton transfers, the most commonly observed contribution to enzyme catalysis. In the bifunctional coenzyme, thiamin diphosphate (ThDP), both aromatic rings participate in catalysis, the thiazolium ring as an electrophilic covalent catalyst and the 4'-aminopyrimidine as acid-base catalyst involving its 1',4'-iminopyrimidine tautomeric form. Two of four ionization and tautomeric states of ThDP are well characterized via circular dichroism spectral signatures on several ThDP superfamily members. Yet, the method is incapable of providing information about specific proton locations, which in principle may be accessible via NMR studies. To determine the precise ionization/tautomerization states of ThDP during various stages of the catalytic cycle, we report the first application of solid-state NMR spectroscopy to ThDP enzymes, whose large mass (160,000-250,000 Da) precludes solution NMR approaches. Three de novo synthesized analogues, [C2,C6'-(13)C(2)]ThDP, [C2-(13)C]ThDP, and [N4'-(15)N]ThDP used with three enzymes revealed that (a) binding to the enzymes activates both the 4'-aminopyrimidine (via pK(a) elevation) and the thiazolium rings (pK(a) suppression); (b) detection of a pre-decarboxylation intermediate analogue using [C2,C6'-(13)C(2)]ThDP, enables both confirmation of covalent bond formation and response in 4'-aminopyrimidine ring's tautomeric state to intermediate formation, supporting the mechanism we postulate; and (c) the chemical shift of bound [N4'-(15)N]ThDP provides plausible models for the participation of the 1',4'-iminopyrimidine tautomer in the mechanism. Unprecedented detail is achieved about proton positions on this bifunctional coenzyme on large enzymes in their active states.

Determination of pre-steady-state rate constants on the Escherichia coli pyruvate dehydrogenase complex reveals that loop movement controls the rate-limiting step.

Spectroscopic identification and characterization of covalent and noncovalent intermediates on large enzyme complexes is an exciting and challenging area of modern enzymology. The Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), consisting of multiple copies of enzymic components and coenzymes, performs the oxidative decarboxylation of pyruvate to acetyl-CoA and is central to carbon metabolism linking glycolysis to the Krebs cycle. On the basis of earlier studies, we hypothesized that the dynamic regions of the E1p component, which undergo a disorder-order transition upon substrate binding to thiamin diphosphate (ThDP), play a critical role in modulation of the catalytic cycle of PDHc. To test our hypothesis, we kinetically characterized ThDP-bound covalent intermediates on the E1p component, and the lipoamide-bound covalent intermediate on the E2p component in PDHc and in its variants with disrupted active-site loops. Our results suggest that formation of the first covalent predecarboxylation intermediate, C2α-lactylthiamin diphosphate (LThDP), is rate limiting for the series of steps culminating in acetyl-CoA formation. Substitutions in the active center loops produced variants with up to 900-fold lower rates of formation of the LThDP, demonstrating that these perturbations directly affected covalent catalysis. This rate was rescued by up to 5-fold upon assembly to PDHc of the E401K variant. The E1p loop dynamics control covalent catalysis with ThDP and are modulated by PDHc assembly, presumably by selection of catalytically competent loop conformations. This mechanism could be a general feature of 2-oxoacid dehydrogenase complexes because such interfacial dynamic regions are highly conserved.

Marine phytoplankton responses to oil and dispersant exposures: Knowledge gained since the Deepwater Horizon oil spill.

The Deepwater Horizon oil spill of 2010 brought the ecology and health of the Gulf of Mexico to the forefront of the public's and scientific community's attention. Not only did we need a better understanding of how this oil spill impacted the Gulf of Mexico ecosystem, but we also needed to apply this knowledge to help assess impacts from perturbations in the region and guide future response actions. Phytoplankton represent the base of the food web in oceanic systems. As such, alterations of the phytoplankton community propagate to upper trophic levels. This review brings together new insights into the influence of oil and dispersant on phytoplankton. We bring together laboratory, mesocosm and field experiments, including insights into novel observations of harmful algal bloom (HAB) forming species and zooplankton as well as bacteria-phytoplankton interactions. We finish by addressing knowledge gaps and highlighting key topics for research in novel areas.

An efficient nickel catalyst for the reduction of carbon dioxide with a borane.

Nickel hydride with a diphosphinite-based ligand catalyzes the highly efficient reduction of CO(2) with catecholborane, and the hydrolysis of the resulting methoxyboryl species produces CH(3)OH in good yield. The mechanism involves a nickel formate, formaldehyde, and a nickel methoxide as different reduced stages for CO(2). The reaction may also be catalyzed by an air-stable nickel formate.