Structural and mechanistic studies on γ-butyrobetaine hydroxylase

1. Download : Download high-res image (415KB)
2. Download : Download full-size image

Highlights? Crystal structure of γ-butyrobetaine hydroxylase in complex with substrate and inhibitor ? N-terminal Zn-binding domain involved in dimerization ? The clinically used inhibitor, THP, is also a substrate for BBOX ? BBOX catalyzed rearrangement reaction     

Inhibition of 2-oxoglutarate dependent oxygenases

2-Oxoglutarate (2OG) dependent oxygenases are ubiquitous iron enzymes that couple substrate oxidation to the conversion of 2OG to succinate and carbon dioxide. In humans their roles include collagen biosynthesis, fatty acid metabolism, DNA repair, RNA and chromatin modifications, and hypoxic sensing. Commercial applications of 2OG oxygenase inhibitors began with plant growth retardants, and now extend to a clinically used pharmaceutical compound for cardioprotection. Several 2OG oxygenases are now being targeted for therapeutic intervention for diseases including anaemia, inflammation and cancer. In this critical review, we describe studies on the inhibition of 2OG oxygenases, focusing on small molecules, and discuss the potential of 2OG oxygenases as therapeutic targets (295 references).     

Synthesis, structure, and thermochemistry of the formation of the metal-metal bonded dimers [Mo(mu-TeAr)(CO)3(PiP3)]2 (Ar = phenyl, naphthyl) by phosphine elimination from *Mo(TePh)(CO)3(PiPr3)2

The complexes (*TeAr)Mo(CO)3(PiPr3)2 (Ar = phenyl, naphthyl; iPr = isopropyl) slowly eliminate PiPr3 at room temperature in a toluene solution to quantitatively form the dinuclear complexes [Mo(mu-TeAr)(CO)3(PiPr3)]2. The crystal structure of [Mo(mu-Te-naphthyl)(CO)3(PiPr3)]2 is reported and has a Mo-Mo distance of 3.2130 A. The enthalpy of dimerization has been measured and is used to estimate a Mo-Mo bond strength on the order of 30 kcal mol-1. Kinetic studies show the rate of formation of the dimeric chalcogen bridged complex is best fit by a rate law first order in (*TeAr)Mo(CO)3(PiPr3)2 and inhibited by added PiPr3. The reaction is proposed to occur by initial dissociation of a phosphine ligand and not by radical recombination of 2 mol of (*TeAr)Mo(CO)3(PiPr3)2. Reaction of (*TePh)Mo(CO)3(PiPr3)2, with L = pyridine (py) or CO, is rapid and quantitative at room temperature to form PhTeTePh and Mo(L)(CO)3(PiPr3)2, in keeping with thermochemical predictions. The rate of reaction of (*TeAr)W(CO)3(PiPr3)2 and CO is first-order in the metal complex and is proposed to proceed by the associative formation of the 19 e- radical complex (*TePh)W(CO)4(PiPr3)2 which extrudes a *TePh radical.     

Existence of time lag in crystalline to smectic A (K–SmA) phase transition of 4-decyl-4-biphenylcarbonitrile (10CB) liquid crystal

This study explores the presence of time lag in crystalline to smectic A (K–SmA) phase transition of 4-decyl-4-biphenylcarbonitrile (10CB) liquid crystal. A non-isothermal heating and cooling study were performed for 10CB liquid crystal using calorimetric technique where heating scan was performed from 250 to 350 K, and cooling scan was performed from 350 to 250 K. A clear difference in K–SmA phase transition was observed between heating and cooling scans. An attracting inclination effect in K–SmA transition was observed on cooling which is completely absent on heating. The inclination of the K–SmA transition peak increases and shows an existence of time lag during cooling, whereas other family member shows no effect i.e., 8CB. K–SmA peak shows a lower enthalpy with higher activation when compared with 8CB. The presence of time lag and increase in activation can be explained in terms of the density and nature of the material.     

Rapid analysis of trinitite with nuclear forensic applications for post-detonation material analyses

Analysis of post-nuclear detonation materials provides information on the type of device and its origin. Compositional analysis of trinitite glass, fused silicate material produced from the above ground plasma during the detonation of the Trinity nuclear bomb, reveals gross scale chemical and isotopic heterogeneities indicative of limited convective re-homogenization during accumulation into a melt pool at ground zero. Regions rich in weapons grade Pu have also been identified on the surface of the trinitite sample. The absolute and relative abundances of the lanthanoids in the glass are comparable to that of average upper crust composition, whereas the isotopic abundances of key lanthanoids are distinctly non-normal. The trinitite glass has a non-normal Nd isotope composition, with deviations of ?1.75 ± 0.60 ε (differences in parts in 10⁴) in ¹⁴²Nd/¹⁴⁴Nd, +2.24 ± 0.75 ε in ¹⁴⁵Nd/¹⁴⁴Nd, and +1.01 ± 0.38 ε in ¹⁴⁸Nd/¹⁴⁴Nd (all errors cited at 2σ) relative to reference materials: BHVO-2 and Nd-Ames metal. Greater isotopic deviations are found in Gd, with enrichments of +4 ± 1 ε in ¹⁵⁵Gd/¹⁶⁰Gd, +4.19 ± 0.75 ε in ¹⁵⁶Gd/¹⁶⁰Gd, and +3.48 ± 0.52 ε in ¹⁵⁸Gd/¹⁶⁰Gd compared to BHVO-2. The isotopic deviations are consistent with a ²³⁹Pu based fission device with additional ²³⁵U fission contribution and a thermal neutron fluence between 1.4 and 0.97 × 10¹⁵ neutrons/cm².