Induced Correspondence of a Local π‐Aromatic Sextet in Heteroannulenes: Synthesis and Characterization

Acid‐catalyzed [3+3] condensation reactions of two hitherto unknown tripyrrane moieties with pentafluorobenzaldehyde has led to the formation of new generation heteroannulene (4.1.4.1) and mutant heteroannulene (1.1.1.1.1.1). Inclusion of local π‐aromatic sextets, namely the N‐methyl pyrrole rings through β,β‐linkages and α,β‐linkages, has led to the isolation of first ever heteroannulenes cross‐conjugated at four points and two points respectively within the macrocycles.     

Inducing efficiency in oligopolistic markets with increasing returns to scale

We consider a Cournot oligopoly market of firms possessing increasing returns to scale technologies (which may not be identical). It is shown that an external regulating agency can increase total social welfare without running a deficit by offering to subsidize one firm an amount which depends on the output level of that firm and the market price. The firms bid for this contract, the regulator collects the highest bid upfront and subsidizes the highest bidding firm. It is shown that there exists a subsidy schedule such that (i) the regulator breaks even, (ii) the subsidized firm obtains zero net profit and charges a price equal to its average cost, (iii) every other firm willingly exit the market and (iv) market price decreases, consumers are better off and total welfare improves.     

A rapid and sensitive determination of hypoxic radiosensitizer agent nimorazole in rat plasma by LC‐MS/MS and its application to a pharmacokinetic study

A highly sensitive, accurate and robust LC‐MS/MS method was developed and validated for determination of nimorazole (NMZ) in rat plasma using metronidazole (MNZ) as internal standard (IS). The analyte and IS were extracted from plasma by precipitating protein with acetonitrile and were chromatographed using an Agilent Poroshell 120, EC‐C₁₈ column. The mobile phase was composed of a mixture of acetonitrile and 0.1 % formic acid (85:15 v/v). The total run time was 1.5 min and injection volume was 5 μL. Multiple reaction monitoring mode using the transitions of m/z 227.1 → m/z 114.0 for MNZ and m/z 172.10 → m/z 128.1 for IS were monitored on a triple quadrupole mass spectrometer, operating in positive ion mode. The calibration curve was linear in the range of 0.25–200 ng/mL (r² > 0.9996) and the lower limit of quantification was 0.25 ng/mL in the rat plasma samples. Recoveries of NMZ ranged between 88.05 and 95.25%. The precision (intra‐day and inter‐day) and accuracy of the quality control samples were 1.25–8.20% and ?2.50–3.10, respectively. The analyte and IS were found to be stable during all sample storage and analysis procedures. The LC‐MS/MS method described here was validated and successfully applied to pharmacokinetic study in rats. Copyright © 2015 John Wiley & Sons, Ltd.     

Binding affinity of substituted ureido‐benzenesulfonamide ligands to the carbonic anhydrase receptor: A theoretical study of enzyme inhibition

The binding properties of a series of benzenesulfonamide inhibitors (4‐substituted‐ureido‐benzenesulfonamides, UBSAs) of human carbonic anhydrase II (hCA II) enzyme with active site residues have been studied using a hybrid quantum mechanical/molecular mechanical (QM/MM) model. To account for the important docking interactions between the UBSAs ligand and hCA II enzyme, a molecular docking program AutoDock Vina is used. The molecular docking results obtained by AutoDock Vina revealed that the docked conformer has root mean square deviation value less than 1.50 Å compared to X‐ray crystal structures. The inhibitory activity of UBSA ligands against hCA II is found to be in good agreement with the experimental results. The thermodynamic parameters for inhibitor binding show that hydrogen bonding, hydrophilic, and hydrophobic interactions play a major role in explaining the diverse inhibitory range of these derivatives. Additionally, natural bond orbital analysis is performed to characterize the ligand–metal charge transfer stability. The insights gained from this study have great potential to design new hCA‐II inhibitor, 4‐[3‐(1‐p‐Tolyl‐4‐trifluoromethyl‐1H‐pyrazol‐3‐yl)‐ureido]‐benzenesulfonamide, which belongs to the family of UBSA inhibitors and shows similar type of inhibitor potency with hCA II. This work also reveals that a QM/MM model and molecular docking method are computationally feasible and accurate for studying substrate–protein inhibition. © 2013 Wiley Periodicals, Inc.     

Interfacial rheology of mixed layers of food proteins and surfactants

Mixed protein–surfactant adsorption layers at liquid interfaces are described including the thermodynamic basis, the adsorption kinetics and the shear and dilational interfacial rheology. It is shown that due to the protrusion of hydrophobic protein parts into the oil phase the adsorption layers at the water–hexane interface are stronger anchored as compared to the water-air surface. Based on the different adsorption protocols, a sequential and a simultaneous scheme, the peculiarities of complexes between proteins and added surfactants are shown when formed in the solution bulk or at a liquid interface. The picture drawn from adsorption studies is supported by the findings of interfacial rheology.     

Dispersion corrected double high-hybrid and gradient-corrected density functional theory study of light cation–dihydrogen (M+–H2, where M = Li, Na, B and Al) van der Waals complexes

Structure, frequencies, H–H stretching frequency shifts, interaction energy, depth of the potential well and dissociation energy of the light cation–dihydrogen (M⁺–H₂, where M = Li, Na, B, and Al) van der Waals complexes have been studied in detail using dispersion corrected double-hybrid and gradient-corrected density functional methods in conjunction with correlation consistent valence triple-ζ basis set. Equilibrium bond distance and dissociation energy agree very well with the experimental and theoretical values wherever available. The dissociation energies of Li⁺–H₂, B⁺–H₂, Na⁺–H₂, and Al⁺–H₂ van der Waals complexes calculated from the potential energy curves at mPW2PLYP-D/cc-pVTZ level are 4.83, 3.68, 2.42, and 1.25 kcal/mol, respectively, at a distances of 1.95, 2.25, 2.40, and 2.95 Å. Among all these complexes, Al⁺–H₂ complex is comparatively less stable, as their dissociation energy as well as depth of the potential well are smaller compared to others complexes. The symmetry-adapted perturbation theory (SAPT) has been applied to quantify the nature of interactions. The SAPT results show that the contribution of dispersion and induction are significant, although electrostatic dominates.     

Synergistic Role of Bacterial Urease and Carbonic Anhydrase in Carbonate Mineralization

The investigation on the synergistic role of urease (UA) and carbonic anhydrase (CA) in biomineralization of calcium carbonate in Bacillus megaterium suggested that the precipitation of CaCO₃ is significantly faster in bacterial culture than in crude enzyme solutions. Calcite precipitation is significantly reduced when both the enzymes are inhibited in comparison with those of the individual enzyme inhibitions indicating that both UA and CA are crucial for efficient mineralization. Carbonic anhydrase plays a role in hydrating carbon dioxide to bicarbonate, while UA aids in maintaining the alkaline pH that promotes calcification process.