Pentanuclear Ba(II) complex of a macrocyclic ligand

We report here the first pentanuclear Ba(II) complex of a new tri-aza, tri-oxa macrocycle with two carboxymethyl "arms" pending from two N atoms, H2L2. The crystal structure corresponds to the formula [Ba5(H0.375L2)4(ClO4)(CH3CH2OH)(H2O)2](ClO4)2.5 x 9.5H2O and reveals the presence of four molecules of the ligand surrounding five Ba(II) ions, giving rise to an unusual structure with the metal ions inside a spherical organic cavity.     

The Role of Intramolecular Hydrogen Bonds vs. Other Weak Interactions on the Conformation of Hyponitrous Acid and Its Mono- and Dithio-Derivatives

High level ab initio and density functional theory calculations have been carried out to investigate the relative stability of the different conformers of hyponitrous acid and its mono- and dithio-derivatives. Geometries and vibrational frequencies were obtained at the B3LYP/6-311+G(d,p) level and final energies through B3LYP/6-311++G(3df,2pd) single point calculations. The reliability of this theoretical scheme has been assessed by comparing these DFT results with those obtained at the G3 level of theory, for some suitable cases. The cis conformers of hyponitrous acid and its mono- and dithio-derivatives are systematically more stable than the trans ones because in the cis conformation a dative interaction between the nitrogen-lone pairs and the σ_NX^* antibonding orbital is significantly favored. Quite interestingly, in general, the conformers presenting an intramolecular hydrogen bond (IHB) are not the global minima of the corresponding potential energy surfaces and only for hyponitrous acid the conformer with a OH ⋅s O IHB is slightly more stable than the cis conformer without IHB. The low stability of the tautomers with IHB is closely related with another weak intramolecular interaction which involves the lone-pairs of the chalcogen atoms and the π_NN^* antibondig orbital, and which is significantly perturbed when the IHB is formed.     

Estimating the PDMS-Coated, SPME-Fibre/Water- and Fibre/Gas-Partition Coefficients of Chlorinated Ethenes by Headspace-SPME

In this work, a simple, fast and reproducible method is presented for the determination of fibre/liquid-phase and fibre/gas-phase partition coefficients of five chlorinated ethenes on a poly-(dimethylsiloxane), PDMS-coated, solid-phase microextraction fibre, by employing a headspace HS-SPME coupled with gas chromatography. The partition coefficients were estimated by a numerical method using a Level-I fugacity method coupled with parameter-estimation software. Dimensionless partition coefficients between SPME fibre and liquid as well as gas phases were obtained at temperatures of 10 °C, 25 °C and 30 °C. The partition coefficients of the fibre and the gas phase, K _fg, increase with decreasing temperature by a factor of ≈2 to 6, and they are directly proportional to the linear slope of the regression line. The same tendency is observed for the partition coefficient of the fibre and liquid phase, K _fw, in a factor ≈1.2 to 2.0. The sorption enthalpy is higher in the gas phase; therefore, the sorption onto the fibre is favoured at lower temperatures. The correlation of the log K _ow versus log K _fw and log K _oa versus log K _fg shows a linear relationship with the number of chlorine atoms in the C = C molecule. Long-term experiments resulted in sorption to Teflon surfaces and possible losses in 43 mL vials, not observed in 250 mL Boston bottles.     

Voltammetric behavior of zaleplon and its differential pulse polarographic determination in capsules

In this work both the electrochemical behavior and the analysis of the hypnotic pyrazolopyrimidine derivative zaleplon were studied. Zaleplon in ethanol-0.1M Britton Robinson buffer solution (30-70) showed 2 irreversible, well-defined cathodic responses in the pH range of 2-12 using differential pulse polarography (DPP), tast polarography, and cyclic voltammetry. From chronocoulometric studies, it was possible to conclude that one electron was transferred in each reduction peak or wave. For analytical purposes, the DPP technique working at pH 4.5 for peak I was selected, which exhibited adequate repeatability, reproducibility, and selectivity. The recovery was 99.97 +/- 1.52%, and the detection and quantitation limits were 5.13 x 10(-7)M and 1.11 x 10(-6)M, respectively. The DPP method was applied successfully to the individual assay of capsules in order to verify the content uniformity of zaleplon. Treatment of the sample is not required because the excipients do not interfere, the method is not time consuming, and it is less expensive than column liquid chromatography.     

Gas-phase interaction of H2S with O2: A kinetic and quantum chemistry study of the potential energy surface

Quantum chemical calculations were carried out to study the interaction of hydrogen sulfide with molecular oxygen in the gas phase. The basic mechanism, the rates of reaction, and the potential energy surface were calculated. Isomers and transition states that connect the reactants with intermediates and products of reaction were identified using the G2 method and B3LYP/6-311+G(3df,2p) functional. Hydrogen abstraction to form HO2 + SH is the dominant product channel and proceeds through a loose transition state well-described at the level of calculation employed. The temperature dependence of the rate coefficient in the range 300-3000 K has been determined on the basis of the ab initio potential energy surface and with variational transition-state theory. The reaction is 169.5 kJ mol(-1) endothermic at 0 K with a rate constant given by 2.77 x 10(5) T(2.76) exp(-19 222/T) cm3 mol(-1) s(-1) and should proceed slowly under atmospheric thermal conditions, but it offers a route to the initiation of H2S combustion at relatively low temperatures.     

Hydrogen bonding in redox-modulated molecular recognition. An experimental and theoretical investigation

Two receptors, a diaminotriazine derivative (DAT) and diamidopyridine (DAP), are complementary to the electroactive naphthalimide (N) through three-point hydrogen bonding. The association constants of the two receptors were evaluated for both the fully oxidized and the radical anion forms of N. In the oxidized state, the two receptors displayed identical binding constants. Diamidopyridine, however, lowers the reduction potential of naphthalimide to a far greater extent than does diaminotriazine, indicating a greater affinity for diamidopyridine by naphthalimide in the radical anion form. This behavior was mirrored by EPR experiments that showed small deviations from the hyperfine coupling pattern of N(red) in the presence of DAT, with greater effects seen for the N(red).DAP complex. Computational simulations using the UB3LYP/6-311+G(d,p)//UHF/6-31G(d) hybrid gave theoretical hyperfine constants in good quantitative agreement with the experimental results. Using this correlation, we determined that electrostatics and hydrogen bond polarizability play key roles in controlling redox-modulated molecular recognition.     

Characterization and de novo sequencing of Atlantic salmon vitellogenin protein by electrospray tandem and matrix-assisted laser desorption/ionization mass spectrometry

Vitellogenin (VTG) is a protein produced by the liver of oviparous animals in response to circulating estrogens. In the plasma of males and immature females, VTG is undetectable. VTG has been used as a biomarker for exposure to endocrine disruptors in many species. In the present study, characterization of intact Atlantic salmon VTG was effected using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI ToF MS). Tryptic digest peptides were analyzed by MALDI ToF MS to obtain a peptide mass fingerprint. De novo sequencing of the tryptic peptides used low-energy collisionally-induced dissociation (CID) in an electrospray ionization quadrupole-ToF orthogonal hybrid mass spectrometer (ESI Q-ToF MS/MS). The interpretation of the product-ion spectra obtained from the ESI Q-ToF MS/MS was done by Lutefisk, a computer-based software algorithm. The molecular mass of the intact protein was found to be 187335 Da. A total of 14 tryptic peptides were sequenced and compared with the complete rainbow trout VTG and the partial Atlantic salmon VTG sequences found in the Swiss-Prot database. De novo sequencing by CID MS/MS of 11 Atlantic salmon tryptic digest peptides with selected precursor ions at m/z 788.24, 700.20, 794.75, 834.31, 889.28, 819.79, 865.27, 843.81, 572.20, 573.66 and 561.68 showed high homology with the known sequence of rainbow trout VTG. The last two precursor peptide ions, found at m/z 573.66 and m/z 561.68, also specifically matched the known portion of the Atlantic salmon VTG sequence. Finally, three tryptic precursor peptide ions found at m/z 795.18, 893.28 and 791.05, provided product-ion spectra, which were exclusive to the unsequenced portion of the Atlantic salmon VTG.     

2-Mercaptomethyl-thiazolidines use conserved aromatic–S interactions to achieve broad-range inhibition of metallo-β-lactamases

Infections caused by multidrug resistant (MDR) bacteria are a major public health threat. Carbapenems are among the most potent antimicrobial agents that are commercially available to treat MDR bacteria. Bacterial production of carbapenem-hydrolysing metallo-β-lactamases (MBLs) challenges their safety and efficacy, with subclass B1 MBLs hydrolysing almost all β-lactam antibiotics. MBL inhibitors would fulfil an urgent clinical need by prolonging the lifetime of these life-saving drugs. Here we report the synthesis and activity of a series of 2-mercaptomethyl-thiazolidines (MMTZs), designed to replicate MBL interactions with reaction intermediates or hydrolysis products. MMTZs are potent competitive inhibitors of B1 MBLs in vitro (e.g., K_i = 0.44 μM vs. NDM-1). Crystal structures of MMTZ complexes reveal similar binding patterns to the most clinically important B1 MBLs (NDM-1, VIM-2 and IMP-1), contrasting with previously studied thiol-based MBL inhibitors, such as bisthiazolidines (BTZs) or captopril stereoisomers, which exhibit lower, more variable potencies and multiple binding modes. MMTZ binding involves thiol coordination to the Zn(ii) site and extensive hydrophobic interactions, burying the inhibitor more deeply within the active site than d/l-captopril. Unexpectedly, MMTZ binding features a thioether–π interaction with a conserved active-site aromatic residue, consistent with their equipotent inhibition and similar binding to multiple MBLs. MMTZs penetrate multiple Enterobacterales, inhibit NDM-1 in situ, and restore carbapenem potency against clinical isolates expressing B1 MBLs. Based on their inhibitory profile and lack of eukaryotic cell toxicity, MMTZs represent a promising scaffold for MBL inhibitor development. These results also suggest sulphur–π interactions can be exploited for general ligand design in medicinal chemistry.

Metallo-β-lactamases (MBLs) are major culprits of resistance to carbapenems in bacteria. A series of thiazolidines are potent MBL inhibitors, restoring the activity of carbapenems. Metal binding and sulphur–π interactions are key to inhibition.