Exploring the Role of L10 Loop in New Delhi Metallo-β-lactamase (NDM-1): Kinetic and Dynamic Studies

Four NDM-1 mutants (L218T, L221T, L269H and L221T/Y229W) were generated in order to investigate the role of leucines positioned in L10 loop. A detailed kinetic analysis stated that these amino acid substitutions modified the hydrolytic profile of NDM-1 against some β-lactams. Significant reduction of k_cat values of L218T and L221T for carbapenems, cefazolin, cefoxitin and cefepime was observed. The stability of the NDM-1 and its mutants was explored by thermofluor assay in real-time PCR. The determination of T_mB and T_mD demonstrated that NDM-1 and L218T were the most stable enzymes. Molecular dynamic studies were performed to justify the differences observed in the kinetic behavior of the mutants. In particular, L218T fluctuated more than NDM-1 in L10, whereas L221T would seem to cause a drift between residues 75 and 125. L221T/Y229W double mutant exhibited a decrease in the flexibility with respect to L221T, explaining enzyme activity improvement towards some β-lactams. Distances between Zn1-Zn2 and Zn1-OH- or Zn2-OH- remained unaffected in all systems analysed. Significant changes were found between Zn1/Zn2 and first sphere coordination residues.     

5‐Amino‐6‐phenyl‐1,6‐di­hydro­pyridazin‐3(2H)‐one

In the title compound, C₁₀H₉N₃O, the pyridazinone moiety is essentially planar and forms a dihedral angle of 49.5 (1)° with the phenyl substituent. The molecular packing is stabilized by van der Waals interactions and hydrogen bonds.     

Carbon Dioxide Capture and Utilization with Isomeric Forms of Bis(amino)-Tagged Zinc Bipyrazolate Metal–Organic Frameworks

Aiming at extending the tagged zinc bipyrazolate metal–organic frameworks (MOFs) family, the ligand 3,3’-diamino-4,4’-bipyrazole ( 3,3’-H₂L ) has been synthesized in good yield. The reaction with zinc(II) acetate hydrate led to the related MOF Zn(3,3’-L) . The compound is isostructural with its mono(amino) analogue Zn(BPZNH₂) and with Zn(3,5-L) , its isomeric parent built with 3,5-diamino-4,4’-bipyrazole. The textural analysis has unveiled its micro-/mesoporous nature, with a BET area of 463 m² g⁻¹. Its CO₂ adsorption capacity (17.4 wt. % CO₂ at p_CO2 = 1 bar and T = 298 K) and isosteric heat of adsorption (Q_st = 24.8 kJ mol⁻¹) are comparable to that of Zn(3,5-L) . Both Zn(3,3’-L) and Zn(3,5-L) have been tested as heterogeneous catalysts in the reaction of CO₂ with the epoxides epichlorohydrin and epibromohydrin to give the corresponding cyclic carbonates at T = 393 K and p_CO2 = 5 bar under solvent- and co-catalyst-free conditions. In general, the conversions recorded are higher than those found for Zn(BPZNH₂), proving that the insertion of an extra amino tag in the pores is beneficial for the epoxidation catalysis. The best catalytic match has been observed for the Zn(3,5-L) /epichlorohydrin couple, with 64 % conversion and a TOF of 5.3 mmol(carbonate) (mmol_Zn)⁻¹ h⁻¹. To gain better insights on the MOF-epoxide interaction, the crystal structure of the [epibromohydrin@ Zn(3,3’-L) ] adduct has been solved, confirming the existence of Br⋅⋅⋅(H)−N non-bonding interactions. To our knowledge, this study represents the first structural determination of a [epibromohydrin@MOF] adduct.     

Square-planar d8 metal mixed-ligand dithiolene complexes as second order nonlinear optical chromophores: Structure/property relationship

The structure/property relationship of square-planar d⁸ metal push/pull mixed-ligand dithiolene complexes is discussed to provide suitable tools to chemists for tailoring compounds with predictable optical properties. These complexes exhibit a typical HOMO–LUMO electronic transition which falls at low energies (vis–NIR region). Substituents at the dithiolene core affect the energy of the frontier orbitals and mixed-ligand complexes based on two different ligands give rise to an asymmetric-symmetric distribution of the charge according to the differences in the push/pull character of the two ligands. Where the push/pull character of the two ligands is significantly different, a π localized electron distribution occurs. The pull ligand (dithiolate) contributes mostly to the HOMO, the push ligand (dithione) mostly to the LUMO, and the HOMO–LUMO transition has ligand-to-ligand charge-transfer (CT) character with some contribution of the metal. These chromophores exhibit negative solvatochromism and molecular first hyperpolarizability.Where the difference in the push/pull character of the two ligands is small, a π delocalized electron distribution occurs and the chromophores exhibit optical features typical of symmetrical complexes (NIR dyes, no second order NLO activity).Structural data, spectroscopic and electrochemical features reflect the π-delocalized/localized electron distribution, and suitable markers such as λ_max, ?; ν(CC); reduction potentials work well to distinguish the limiting forms and to predict optical properties.Analogies in the optical features exhibited by d⁸ metal diimino–dithiolate complexes are highlighted.     

Approximation of the variance gamma model with a finite mixture of normals

We investigate the possibility of approximating the variance gamma distribution with a finite mixture of normals. Therefore, we apply this result to derive a simple historical estimation procedure by means of the Expectation Maximization algorithm.     

Size control of Si nanocrystals by two-step rapid thermal annealing of sputtered Si-rich oxide/SiO2 superlattice

Controllable size of silicon (Si) nanocrystals can be achieved by a two-step rapid thermal annealing technique consisting of rapid annealing at 1000°C in nitrogen ambient and rapid oxidation at 600–800°C of a radio frequency magnetron co-sputtered Si-rich oxide/SiO₂ superlattice structure. The photoluminescence (PL) spectra related to Si nanocrystals were observed in the visible range (600–900 nm). After rapid oxidation, the size of the nanocrystals was reduced and the quality of the Si nanocrystal/SiO₂ interface was improved, resulting in a blue shift and an increase of the PL peak intensity. Finally, annealing in air increases the PL intensity further.     

Comparative thermogravimetric and adsorption study of highly ordered mesoporous materials

A comparative study was carried out for highly ordered mesoporous materials using high resolution thermogravimetry (HR-TG) and adsorption techniques. These materials were synthesized with mixed surfactants of various alkyl chain lengths. For thermogravimetry measurements n-butanol was used to probe the adsorbent surface and high-resolution TG curves as well as their 1st and 2nd derivatives were obtained for this probe molecule. It is shown that the values of the mesopore volume and specific surface area evaluated from TG data are in a good agreement with those evaluated from low-temperature nitrogen adsorption isotherms. This comparative study was performed to confirm the usefulness of the HR-TG technique as an alternative method for evaluation of the mesopore volume and specific surface area of ordered mesoporous materials.     

Synthesis,Crystal and Molecular Structures of the Novel Compounds 4,7-Dithio-5,6-Diselenocino- [1,2b:3,4b']-Diimidazolyl-1,3,8,10-Tetrabutyl 2,9-Dithione and -2,9-Diselone

The sulfurization reaction with Lawesson's reagent on a series of 1,3-dialkyl imidazolidine-2-selone-4,5-diones in toluene gave depending on the reaction conditions, the compounds 4,7-dithio, 5,6-diselenocino[1,2b:3,4b']diimidazolyl-1,3,8,10-tetraalkane-2,9-dithione and -2,9-diselone. The structural characterization of the tetrabutyl derivatives are reported.