Kinetics of template-directed pyrophosphate-linked dideoxyguanylate synthesis as a function of 2-MeImpdG and poly(C) concentration: insights into the mechanism.

Aqueous solutions of deoxyguanosine 5'-monophosphate 2-methylimidazolide, 2-MeImpdG, yield primarily deoxyguanosine 5'-monophosphate, 5'dGMP, and pyrophosphate-linked dideoxyguanylate, dG5'ppdG, abbreviated G2p (see Chart 1). The initial rate of G2p formation, d[G2p]/dt in M h-1, determined at 23 degrees C, pH 7.8, 1.0 M NaCl and 0.2 M Mg2+ by timed high-performance liquid chromatography (HPLC) analysis, exhibits a second-order dependence on 2-MeImpdG concentration, [G]o, indicating a bimolecular mechanism of dimerization in the range 0.02 M < or = [G]o < or = 0.09 M. In the presence of polycytidylate, poly(C), G2p synthesis is accelerated and oligodeoxyguanylate products are formed by incorporation of 2-MeImpdG molecules. The kinetics of G2p formation as a function of both monomer and polymer concentration, expressed in C equivalents, were also determined under the above conditions and exhibited a complex behavior. Specifically, at a constant [poly(C)], values of d[G2p]/dt typically increased with [G]o with a parabolic upward curvature. At a constant [G]o, values of d[G2p]/dt increase with [poly(C)], but level off at the higher poly(C) concentrations. As [G]o increases this saturation occurs at a higher poly(C) concentration, a result opposite to expectation for a simple complexation of two reacting monomers with the catalyst prior to reaction. Nevertheless, these results are shown to be quantitatively consistent with a template-directed (TD) mechanism of dimerization where poly(C) acts as the template to bind 2-MeImpdG in a cooperative manner and lead, for the first time, to the formulation of principles that govern template-directed chemistry. Analysis of the kinetic data via a proposed TD cooperative model provides association constants for the affinity between polymer and monomer and the intrinsic reactivity of 2-MeImpdG toward pyrophosphate synthesis. To the best of our knowledge, poly(C)/2-MeImpdG is the first system that could serve as a textbook example of a TD reaction under conditions such that the template is fully saturated by monomers and under conditions that it is not.     

Tunable middle infrared radiation with HgGa2S4 crystal

Optical properties of orange phased HgGa₂S₄ crystal is investigated. Generation of tunable middle infrared radiation by second harmonic of tunable CO₂ laser radiation has been demonstrated. Second harmonic conversion efficiency with respect to other infrared crystal has also been discussed.     

Effect of AgNO3 additive/doping on microstructure and superconductivity of the Pb doped Hg: 1223 thin film prepared through spray pyrolysis

We report successful fabrication of Ag doped Hg:1223 films by reacting Ba₂Ca_2.3Cu_3.3O_z(Ag_y): y=0, 0.02, 0.025, 0.05, 0.1 and 0.2 precursors deposited by spray pyrolysis on SrTiO₃ (100) substrates, in controlled Hg+Pb ambient, in an evacuated sealed quartz tube at 820 °C for 4 h. The effects of AgNO₃ addition on the superconducting properties of Hg/(Pb):1223 films are studied. The addition of low concentration of silver e.g. y≈0.025 results in a slight increase in T_c (R=0) from 125 to 126 K and the dc critical current density (J_c) decreases with the increasing Ag in Hg(Pb):1223 (Ag_y) films. The microstructural details exhibit the curious characteristics of spiral like features for lower concentrations of silver i.e. up to y=0.05. These improvements are believed to be due to the liberation of oxygen through the dissociation of AgNO₃ at higher temperature and passivation of weak link effects through the segregation of silver at these grain boundaries. The addition of silver content y≥0.05 resulted in the decrease in transition temperature. The J_c is observed to decrease steadily with increasing Ag content. The microstructural features, e.g. spiral are also found to deteriorate with increasing silver content. The deterioration in superconducting properties at high Ag content is believed to be mainly due to the formation of Ag-Hg amalgam.     

Alkyne‐Mediated Approach to the Synthesis of (4R,5R)‐5‐Hydroxy‐4‐decanolide and (−)‐Muricatacin

The asymmetric synthesis of two naturally occurring 5‐hydroxy‐γ‐butyrolactones, (4R,5R)‐5‐hydroxy‐4‐decanolide ( 1a ) and (?)‐muricatacin ( 2 ), is described using a general alkyne‐mediated strategy. The key steps involved are Sonogashira coupling for the desired carbon‐chain extension followed by Sharpless asymmetric dihydroxylation to construct the hydroxy‐lactone framework.     

Integrated quality by design (QbD) and design of experiments (DoE) approach for UFLC determination of telaprevir in rat serum

An ultrafast liquid chromatographic bioanalytical method was developed and validated for the determination of telaprevir in Wistar albino rat serum. Principles of quality by design (QbD) were implemented for enhancing the bioanalytical liquid–liquid extraction of telaprevir from rat serum. A Box–Behnken design was utilized in the studies by selecting extraction time, centrifugation speed, and vortex time as the critical method variables for evaluating their effect on the critical analytical attribute, i.e., %recovery of telaprevir. Chromatographic separation was achieved within a run time of 10?min using a C-18 column and mobile phase comprising of methanol:borate buffer of pH 9 (90:10 v/v) flowing at 1.2?mL/min. Photodiode array detection was performed at 270?nm. Results of validation studies were satisfactory. The method was linear over a concentration of 25–10,000?ng/mL. Limit of detection for the developed method was 10?ng/mL. Further, design of experiments (DoE) used for inter-day accuracy and precision study suggested superior method reliability. This integrated QbD- and DoE-based approach ensured the development of a validated and reliable analytical method for optimum bioanalysis of telaprevir in biological matrix.     

Steric-effect induced alterations in streaming potential and energy transfer efficiency of non-newtonian fluids in narrow confinements

In this work, we explore the possibilities of utilizing the combined consequences of interfacial electrokinetics and rheology toward augmenting the energy transfer efficiencies in narrow fluidic confinements. In particular, we consider the exploitation of steric effects (i.e., effect of finite size of the ionic species) in non-Newtonian fluids over small scales, to report dramatic augmentations in the streaming potential, for shear-thickening fluids. We first derive an expression for the streaming potential considering strong electrical double layer interactions in the confined flow passage and the consequences of the finite conductance of the Stern layer, going beyond the Debye-Hu?ckel limit. With a detailed accounting for the excluded volume effects of the ionic species and their interaction with pertinent interfacial phenomena of special type of rheological fluids such as the power law fluids in the above-mentioned formalism, we demonstrate that a confluence of the steric interactions with the non-Newtonian transport characteristics may result in giant augmentations in the energy transfer efficiency for shear-thickening fluids under appropriate conditions.     

Examining the lateral displacement of HL60 cells rolling on asymmetric P-selectin patterns

The lateral displacement of cells orthogonal to a flow stream by rolling on asymmetrical receptor patterns presents a new opportunity for the label-free separation and analysis of cells. Understanding the nature of cell rolling trajectories on such substrates is necessary to the engineering of substrates and the design of devices for cell separation and analysis. Here, we investigate the statistical nature of cell rolling and the effect of pattern geometry and flow shear stress on cell rolling trajectories using micrometer-scale patterns of biomolecular receptors with well-defined edges. Leukemic myeloid HL60 cells expressing the PSGL-1 ligand were allowed to flow across a field of patterned lines fabricated using microcontact printing and functionalized with the P-selectin receptor, leveraging both the specific adhesion of this ligand-receptor pair and the asymmetry of the receptor pattern inclination angle with respect to the fluid shear flow direction (α = 5, 10, 15, and 20°). The effects of the fluid shear stress magnitude (τ = 0.5, 1, 1.5, and 2.0 dyn/cm(2)), α, and P-selectin incubation concentration were quantified in terms of the rolling velocity and edge tracking length. Rolling cells tracked along the inclined edges of the patterned lines before detaching and reattaching on another line. The detachment of rolling cells after tracking along the edge was consistent with a Poisson process of history-independent interactions. Increasing the edge inclination angle decreased the edge tracking length in an exponential manner, contrary to the shear stress magnitude and P-selectin incubation concentration, which did not have a significant effect. On the basis of these experimental data, we constructed an empirical model that predicted the occurrence of the maximum lateral displacement at an edge angle of 7.5°. We also used these findings to construct a Monte Carlo simulation for the prediction of rolling trajectories of HL60 cells on P-selectin-patterned substrates with a specified edge inclination angle. The prediction of lateral displacement in the range of 200 μm within a 1 cm separation length supports the feasibility of label-free cell separation via asymmetric receptor patterns in microfluidic devices.     

An efficient biomaterial supported bifunctional organocatalyst (ES-SO3- C5H5NH+) for the synthesis of β-amino carbonyls

A biomaterial supported organocatalyst, readily synthesized by the reaction of chemically modified sulfonic group containing expanded corn starch with pyridine exhibited excellent catalytic activity for the synthesis of β-amino carbonyls in excellent yields via aza-Michael addition of amines to electron deficient alkenes. A remarkable enhancement in the reaction rates was observed with the prepared bifunctional organocatalyst in comparison to the either starch grafted sulfonic acid or the corresponding homogeneous pyridinium p-toluenesulfonate.     

Multimodal approaches of the hydroalcoholic extract of Diospyros peregrina fruits in diabetic therapy

The matured fruits of Diospyros peregrina possess significant antidiabetic activity. The present investigation was undertaken to evaluate the target of action of the hydroalcoholic extract of D. peregrina fruit in diabetic pathophysiology. The extract was tested in vitro for inhibition of glucose absorption by α-amylase inhibition assay, glucose uptake study by isolated rat hemidiaphragm method and free radical scavenging activity by DPPH method. The extract exhibited significant α-amylase inhibition (IC?? 136.5 μg mL?1), peripheral glucose utilisation and radical scavenging (IC?? 167.5 μg mL?1) activity. From the results, it may be concluded that the hydroalcoholic extract of D. peregrina fruit can counteract diabetes by multiple mechanisms, namely inhibition of carbohydrate absorption, improving peripheral glucose utilisation and antioxidant defence.     

Synthesis of novel quinoline analogues of nimesulide: An unusual observation

Reduction of nimesulide followed by treating the N‐acyl derivative of resulting arylamine with Vilsmeier‐Haack reagent provided novel 2‐chloro‐3‐formylquinoline derivatives. The construction of quinoline ring using Vilsmeier‐Haack reagent afforded an unexpected compound, N‐(2‐chloro‐3‐formyl‐7‐phenoxy quinolin‐6‐yl)formamide, in addition to the expected product. The structure of this unexpected quinoline derivative was established via single‐crystal X‐ray analysis and its formation could be explained by an unprecedented N‐S bond cleavage under Vilsmeier‐Haack reaction conditions. The 2‐chloro‐3‐formylquinoline derivatives obtained were converted to a number of corresponding Schiff bases with potential pharmacological importance. J. Heterocyclic Chem., 2011.