Development of a new fluorescence ratiometric switch for endogenous hypochlorite detection in monocytes of diabetic subjects by dye release method

Increased oxidative stress in metabolic complications like type 2 diabetes, dyslipidemia and cardiovascular disorders exerts potential health hazards in many facets. Enhanced production of reactive oxygen species (ROS) due to increased oxidative stress promotes the damage of many biologically important macromolecules. Hypochlorous acid (HOCl), a microbicidal agent is also known to be an important ROS sub-species. An enhanced generation of endogenous HOCl due to diseased condition therefore can be detrimental to health. In present work, a new quinoline-diaminomaleonitrile based probe (HQMN) has been designed for the selective detection of hypochlorite. The probe in hand shows a selective ratiometric emission change towards OCl^?. The probe behaves as a highly selective and sensitive tool for the detection of OCl^? over other analytes with a fast response time (within 100 s). Bioimaging study revealed that HQMN can detect endogenous OCl^? in human monocytes and an increase in endogenous HOCl concentration has been witnessed in diabetic condition compared to healthy control. Thus HQMN can be used as an excellent fluorescent probe for dynamic tracking of hypochorite in living biological cells especially to identify diabetic conditions.     

Gallium and indium dithiocarboxylates: Synthesis, spectroscopic characterization and structure of [MeGa(S2Ctol)2]

Several gallium and indium dithiocarboxylate complexes of the type [Me_nM(S₂CR)_3−n] (M = Ga, In; n = 0, 1, 2; R = phenyl (Ph), p-tolyl (tol), mesityl (Mes)) have been synthesized. These complexes were characterized by elemental analysis, IR, UV-vis and NMR (¹H,¹³C{¹H}) spectroscopy. Structure of [MeGa(S₂Ctol)₂] was established by X-ray crystallography. The gallium atom adopts a distorted five coordinate geometry which is intermediate between trigonal bipyramidal and square pyramidal configurations. The complex [Me₂InS₂Ctol] underwent a two-step thermal decomposition leading to the formation of tetragonal β-In₂S₃.     

Rationalizing fragment based drug discovery for BACE1: insights from FB-QSAR,FB-QSSR,multi objective (MO-QSPR) and MIF studies

The ability to identify fragments that interact with a biological target is a key step in FBDD. To date, the concept of fragment based drug design (FBDD) is increasingly driven by bio-physical methods. To expand the boundaries of QSAR paradigm, and to rationalize FBDD using In silico approach, we propose a fragment based QSAR methodology referred here in as FB-QSAR. The FB-QSAR methodology was validated on a dataset consisting of 52 Hydroxy ethylamine (HEA) inhibitors, disclosed by GlaxoSmithKline Pharmaceuticals as potential anti-Alzheimer agents. To address the issue of target selectivity, a major confounding factor in the development of selective BACE1 inhibitors, FB-QSSR models were developed using the reported off target activity values. A heat map constructed, based on the activity and selectivity profile of the individual R-group fragments, and was in turn used to identify superior R-group fragments. Further, simultaneous optimization of multiple properties, an issue encountered in real-world drug discovery scenario, and often overlooked in QSAR approaches, was addressed using a Multi Objective (MO-QSPR) method that balances properties, based on the defined objectives. MO-QSPR was implemented using Derringer and Suich desirability algorithm to identify the optimal level of independent variables (X) that could confer a trade-off between selectivity and activity. The results obtained from FB-QSAR were further substantiated using MIF (Molecular Interaction Fields) studies. To exemplify the potentials of FB-QSAR and MO-QSPR in a pragmatic fashion, the insights gleaned from the MO-QSPR study was reverse engineered using Inverse-QSAR in a combinatorial fashion to enumerate some prospective novel, potent and selective BACE1 inhibitors.     

Effects of annealing temperature on shape transformation and optical properties of germanium quantum dots

The influences of thermal annealing on the structural and optical features of radio frequency(rf) magnetron sputtered self-assembled Ge quantum dots(QDs) on Si(100) are investigated.Preferentially oriented structures of Ge along the(220) and(111) directions together with peak shift and reduced strain(4.9%to 2.7%) due to post-annealing at 650 ℃ are discerned from x-ray differaction(XRD) measurement.Atomic force microscopy(AFM) images for both pre-annealed and post-annealed(650 ℃) samples reveal pyramidal-shaped QDs(density ~ 0.26×10~(11) cm~(-2)) and dome-shape morphologies with relatively high density ~ 0.92×10~(11) cm~(-2),respectively.This shape transformation is attributed to the mechanism of inter-diffusion of Si in Ge interfacial intermixing and strain non-uniformity.The annealing temperature assisted QDs structural evolution is explained using the theory of nucleation and growth kinetics where free energy minimization plays a pivotal role.The observed red-shift ~ 0.05 eV in addition to the narrowing of the photoluminescence peaks results from thermal annealing,and is related to the effect of quantum confinement.Furthermore,the appearance of a blue-violet emission peak is ascribed to the recombination of the localized electrons in the Ge-QDs/SiO_2 or GeO_x and holes in the ground state of Ge dots.Raman spectra of both samples exhibit an intense Ge-Ge optical phonon mode which shifts towards higher frequency compared with those of the bulk counterpart.An experimental Raman profile is fitted to the models of phonon confinement and size distribution combined with phonon confinement to estimate the mean dot sizes.A correlation between thermal annealing and modifications of the structural and optical behavior of Ge QDs is established.Tunable growth of Ge QDs with superior properties suitable for optoelectronic applications is demonstrated.     

A Triphenyl Amine‐Based Solvatofluorochromic Dye for the Selective and Ratiometric Sensing of OCl− in Human Blood Cells

A new visible‐light‐excitable fluorescence ratiometric probe for OCl^? has been developed based on a triphenylamine‐diamiomaleonitrile (TAM) moiety. The structure of the dye was confirmed by single‐crystal X‐ray analysis. It behaves as a highly selective and sensitive probe for OCl^? over other analytes with a fast response time (～100 s). OCl^? reacts with the probe leading to the formation of the corresponding aldehyde in a mixed‐aqueous system. The detection limit of the probe is in the 10^?8 M range. The probe (TAM) also exhibits solvatofluorochromism. Changing the solvent from non‐polar to polar, the emission band of TAM largely red‐shifted. Moreover, the probe shows an excellent performance in real‐life application in detecting OCl^? in human blood cells. The experimentally observed changes in the structure and electronic properties of the probe after reaction with OCl^? were studied by DFT and TDDFT computational calculations.     

Production of l-asparaginase, an anticancer agent, from Aspergillus niger using agricultural waste in solid state fermentation

This article reports the production of high levels of l-asparaginase from a new isolate of Aspergillus niger in solid state fermentation (SSF) using agrowastes from three leguminous crops (bran of Cajanus cajan, Phaseolus mungo, and Glycine max). When used as the sole source for growth in SSF, bran of G. max showed maximum enzyme production followed by that of P. mungo and C. cajan. A 96-h fermentation time under aerobic condition with moisture content of 70%, 30 min of cooking time and 1205–1405 μ range of particle size in SSF appeared optimal for enzyme production. Enzyme yield was maximum (40.9±3.35 U/g of dry substrate) at pH 6.5 and temperature 30±2°C. The optimum temperature and pH for enzyme activity were 40°C and 6.5, respectively. The study suggests that choosing an appropriate substrate when coupled with process level optimization improves enzyme production markedly. Developing an asparaginase production process based on bran of G. max as a substrate in SSF is economically attractive as it is a cheap and readily available raw material in agriculture-based countries.     

Dynamics of networking agents competing for high centrality and low degree

We model a system of networking agents that seek to optimize their centrality in the network while keeping their cost, the number of connections they are participating in, low. Unlike other game-theory based models for network evolution, the success of the agents is related only to their position in the network. The agents use strategies based on local information to improve their chance of success. Both the evolution of strategies and network structure are investigated. We find a dramatic time evolution with cascades of strategy change accompanied by a change in network structure. On average the network self-organizes to a state close to the transition between a fragmented state and a state with a giant component. Furthermore, with increasing system size both the average degree and the level of fragmentation decreases.     

p-adic string theories provide lattice Discretization to the ordinary string worldsheet

A class of models called p-adic strings is useful in understanding the tachyonic instability of string theory. These are found to be empirically related to the ordinary strings in the p-->1 limit. We propose that these models provide discretization for the string worldsheet and argue that the limit is naturally thought of as a continuum limit in the sense of the renormalization group.     

Metallacrown ethers with a symmetric bis(phosphite) ligand derived from 1,2-bis-(2-hydroxyethoxy)benzene: Synthesis, characterization and hydroformylation of styrene

To better understand the effects of ligand configuration on hydroformylation reactions carried out in the presence of LiBPh₄·3dme (dme = 1,2-dimethoxyethane), a conformationally restrained bis(phosphite) ligand derived from 1,2-bis-(2-hydroxyethoxy)benzene, {[(2,2′-O₂C₁₂H₈)P(C₂H₄O₂)]₂C₆H₄}, 1, has been prepared and its Rh(I) metallacrown ether complex has been evaluated as a catalyst for the hydroformylation of styrene. Both the activity and regioselectivity of the catalyst are sensitive to the amount of the LiBPh₄·3dme added with the activity decreasing by 16% and the regioselectivity for the iso increasing by 9% at a 8:1 LiBPh₄:Rh ratio.Model complexes for the octahedral, cis-Mo(CO)₄(1), 2, and square planar, cis-PtCl₂(1), 3, and cis-PdCl₂(1), 4, complexes in the catalytic cycle has been have been studied using multinuclear NMR spectroscopy and X-ray crystallography. Although the X-ray crystal structure of 2 suggests that the metallacrown ether ring could adopt a configuration capable of binding alkali metal cations, this does not appear to occur in a dichloromethane-d₂ solution of 2 because no shift in the ³¹P NMR resonance 2 is observed upon the addition of an excess of LiBPh₄·3dme. The ³¹P{¹H} NMR spectra of chloroform-d solutions of 2 (in the presence of a catalytic amount of HgCl₂) and of 4 and the X-ray crystal structures of the complexes indicate that the bis(phosphite) ligands are cis coordinated in these complexes in both the solution and in the solid state. This is particularly surprising for 4 because related PdCl₂{Ph₂P(CH₂CH₂O)_nCH₂CH₂PPh₂} (n = 3-5) complexes exhibit both cis-trans and monomer-oligomer equilibria in solution.