Catalytic Reaction Mechanism of Bacterial GH92 α-1,2-Mannosidase: A QM/MM Metadynamics Study

The catalytic mechanism of a -dependent family 92 -mannosidase, which is abundantly present in human gut flora and malfunctions leading to the lysosomal storage disease α-mannosidosis, has been investigated using quantum mechanics/molecular mechanics and metadynamics methods. Computational efforts show that the enzyme follows a conformational itinerary of and the ion serves a dual purpose, as it not only distorts the sugar ring but also plays a crucial role in orchestrating the arrangement of catalytic residues. This orchestration, in turn, contributes to the facilitation of conformers for the ensuing reaction. This mechanistic insight is well-aligned with the experimental predictions of the catalytic pathway, and the computed energies are of the same order of magnitude as the experimental estimations. Hence, our results extend the mechanistic understanding of glycosidases.     

A new (E,E)-dioxime and its mono and heterotrinuclear complexes containing an 18-membered dithiatetraazamacrocycle

The novel (E,E)-dioxime, 5,6:ll,12:17,18-tribenzo-2,3-bis(hydroxyimino)-7,16-dithia-9, 14-dioxo-l,4,10,13-tetraazacyclooctadecane (H₂L) has been synthesized by reacting (E,E)-dichloroglyoxime (2) with 2,3:8,9:14,15-tribenzo-4,13-di-thia-6,11-dioxa-l,7,10,16-tetraazahexzadecane (3), prepared by the reaction of N,N-bis(chloroacetyl)-1, 2-phenylene-diamine (1) with 2-aminothiophenol. Mononuclear complexes (4, 5) of this ligand have been synthesized by reacting the vic-dioxime (H₂L) with K₂PtCl₄ and NiCl₂ · 6H₂O, respectively. Heterotrinuclear complexes (6)and(7) have been prepared by the reaction of (4) and (5) mononuclear complexes with [Cu(MeCN)₄]PF₆. The structures of the vic-dioxime and its mono and trinuclear complexes were identified by elemental analysis, ¹H- and ¹³C-n.m.r, i.r. and m.s. data.     

Synthesis and Metal Complex Formation of Nitrogen-Oxygen Donor Macrocyclic Ligands

Reduction of 2,3:9,10-dibenzo-5,12-diaza-1,8-dioxacylotetradecane-5,11-diene( 1 ) with sodium borohydride in ethanol generates 2,3:9,10-dibenzo-5,12-diaza-1,8-dioxacyclotetradecane( 2 ) in high yield. The macrocyclic ligand 2,3:9,10-dibenzo-5,12-diaza-1,8-dioxacyclotetradecane-N,N′-diacetic acid ( 3 ) has been synthesized and characterized. In addition, reaction of ( 2 ) with an excess of acrylonitrile gives 2,3:9,10-dibenzo-5,12-diaza-1,8-dioxacyclotetradecane-N,N′-di(2-cyanoethyl) ( 4 ). Several new complexes of these ligands with nickel(II), copper(II) and cobalt(II) have been prepared and identified. The structures of these complexes are proposed on the basis of elemental analysis, ¹H, ¹³C-NMR, IR, UV-VIS spectra, magnetic susceptibility and conductivity data.     

Formulation Development of Mirtazapine Liquisolid Compacts: Optimization Using Central Composite Design

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.     

The removal of methylene blue as a remedy of dye-based marine pollution: a photocatalytic perspective

Research on Chemical Intermediates - The effluents containing the discarded water from the textile industry are graded as one of the foremost pollutants in all industrial sectors. The wide...     

Assessing efficiency of public health and medical care provision in OECD countries after a decade of reform

Central European Journal of Operations Research - The objective of this study was to examine the change in efficiency of health care systems of 34 OECD countries between 2000 and 2012, a period...     

Oscillatory Behaviour of a Higher Order Nonlinear Neutral Delay Type Functional Differential Equation with Oscillating Coefficients

In this paper we are concerned with the oscillation of solutions of a certain more general higher order nonlinear neutral type functional differential equation with oscillating coefficients. We obtain two sufficient criteria for oscillatory behaviour of its solutions.     

The relaxed Newton method derivative: Its dynamics and non-linear properties

The dynamic behaviour of the one-dimensional family of maps f(x)=_c2[(a−1)x+_c1]^{−λ/(α−1)}$f\left(x\right)=c_2{[(a-1)x+c_1]}^{-\lambda /(\alpha -1)}$ is examined, for representative values of the control parameters a,_c1$a,c_1$, _c2$c_2$ and λ$\lambda$. The maps under consideration are of special interest, since they are solutions of the relaxed Newton method derivative being equal to a constant a$a$. The maps f(x)$f\left(x\right)$ are also proved to be solutions of a non-linear differential equation with outstanding applications in the field of power electronics. The recurrent form of these maps, after excessive iterations, shows, in an _xn$x_n$ versus λ$\lambda$ plot, an initial exponential decay followed by a bifurcation. The value of λ$\lambda$ at which this bifurcation takes place depends on the values of the parameters a,_c1$a,c_1$ and _c2$c_2$. This corresponds to a switch to an oscillatory behaviour with amplitudes of f(x)$f\left(x\right)$ undergoing a period doubling. For values of a$a$ higher than 1 and at higher values of λ$\lambda$ a reverse bifurcation occurs. The corresponding branches converge and a bleb is formed for values of the parameter _c1$c_1$ between 1 and 1.20. This behaviour is confirmed by calculating the corresponding Lyapunov exponents.     

Effect of a combined treatment using both direct and alternating electric currents on hide bacteria in hide-soak liquor

Inactivation effect of an electric current treatment combining both 188 μA/m² DC and 251 μA/m² AC on Gram negative, Gram positive bacteria and their mixed culture, which were isolated from hides, was separately analyzed. This electric treatment, applied for 16 min was found to be fairly effective in reducing the bacterial cell count (7.10–7.48 log₁₀ colony forming units/mL) to a relatively low level (4.52–4.90 log₁₀ colony forming units/mL). At this level bacterial damage to the hides is reduced in soak liquors. Cheap and efficient electric current may be applied to rapidly reduce the destructive bacterial populations in main hide-soak liquors.