A Substrate-Driven Approach to Determine Reactivities of α,β-Unsaturated Carboxylic Esters Towards Asymmetric Bioreduction

The degree of C?C bond activation in the asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases was studied, and general recommendations to render these "borderline-substrates" more reactive towards enzymatic reduction are proposed. The concept of "supported substrate activation" was developed. In general, an additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates, and α-cyano groups showed little effect. The alcohol moiety of the ester functionality was found to have a strong influence on the reaction rate. Overall, activities were determined by both steric and electronic effects.     

Stress degradation studies and development of stability-indicating TLC-densitometry method for determination of prednisolone acetate and chloramphenicol in their individual and combined pharmaceutical formulations

ABSTRACT: A rapid and reproducible stability indicating TLC method was developed for the determination of prednisolone acetate and chloramphenicol in presence of their degraded products. Uniform degradation conditions were maintained by refluxing sixteen reaction mixtures for two hours at 80°C using parallel synthesizer including acidic, alkaline and neutral hydrolysis, oxidation and wet heating degradation. Oxidation at room temperature, photochemical and dry heating degradation studies were also carried out. Separation was done on TLC glass plates, pre-coated with silica gel 60F-254 using chloroform: methanol (14:1 v/v). Spots at Rf 0.21 ± 0.02 and Rf 0.41 ± 0.03 were recognized as chloramphenicol and prednisolone acetate, respectively. Quantitative analysis was done through densitometric measurements at multiwavelength (243 nm, λmax of prednisolone acetate and 278 nm, λmax of chloramphenicol), simultaneously. The developed method was optimized and validated as per ICH guidelines. Method was found linear over the concentration range of 200-6000 ng/spot with the correlation coefficient (r2 ± S.D.) of 0.9976 ± 3.5 and 0.9920 ± 2.5 for prednisolone acetate and chloramphenicol, respectively. The developed TLC method can be applied for routine analysis of prednisolone acetate and chloramphenicol in presence of their degraded products in their individual and combined pharmaceutical formulations.     

Electron-scale electrostatic solitary waves and shocks: the role of superthermal electrons

The propagation of electron-acoustic solitary waves and shock structures is investigated in a plasma characterized by a superthermal electron population. A three-component plasma model configuration is employed, consisting of inertial (“cold”) electrons, inertialess κ (kappa) distributed superthermal (“hot”) electrons and stationary ions. A multiscale method is employed, leading to a Korteweg-de Vries (KdV) equation for the electrostatic potential (in the absence of dissipation). Taking into account dissipation, a hybrid Korteweg-de Vries-Burgers (KdVB) equation is derived. Exact negative-potential pulse- and kink-shaped solutions (shocks) are obtained. The relative strength among dispersion, nonlinearity and damping coefficients is discussed. Excitations formed in superthermal plasma (finite κ) are narrower and steeper, compared to the Maxwellian case (infinite κ). A series of numerical simulations confirms that energy initially stored in a solitary pulse which propagates in a stable manner for large κ (Maxwellian plasma) may break down to smaller structures or/and to random oscillations, when it encounters a small-κ (nonthermal) region. On the other hand, shock structures used as initial conditions for numerical simulations were shown to be robust, essentially responding to changed in the environment by a simple profile change (in width).     

Photoionization and electron–ion recombination of Cr I

Using the unified method, the inverse processes of photoionization and electron–ion recombination are studied in detail for neutral chromium, (), for the ground and excited states. The unified method based on close-coupling approximation and R-matrix method (i) subsumes both the radiative recombination (RR) and dielectronic recombination (DR) for the total rate and (ii) provides self-consistent sets of photoionization cross sections σ_PI and recombination rates α_RC. The present results show in total photoionization of the ground and excited states an enhancement in the background at the first excited threshold, state of the core. One prominent phot-excitation-of-core (PEC) resonance due to one dipole allowed transition (⁶S-⁶P^o) in the core is found in the photoionization cross sections of most of the valence electron excited states. Structures in the total and partial photoionization, for ionization into various excited core states and ground state only, respectively, are demonstrated. Results are presented for the septet and quintet states with n≤10 and l≤9 of Cr I. These states couple to the core ground state ⁶S and contribute to the recombination rates. State-specific recombination rates are also presented for these states and their features are illustrated. The total recombination rate shows two DR peaks, one at a relatively low temperature, at 630 K, and the other around 40,000 K. This can explain existence of neutral Cr in interstellar medium. Calculations were carried out in LS coupling using a close-coupling wave function expansion of 40 core states. The results illustrate the features in the radiative processes of Cr I and provide photoionization cross sections and recombination rates with good approximation for this astrophysically important ion.     

<Emphasis Type="Italic">v</Emphasis>-Adic maximal extensions,spectral norms and absolute Galois groups

Let (K, v) be a perfect rank one valued field and let ([`(K<sub>v</sub>)],[`(v)]){(\overline{K_{v}},\overline{v})} be the canonical valued field obtained from (K, v) by the unique extension of the valuation [(v)\tilde]{\widetilde{v}} of K _v , the completion of K relative to v, to a fixed algebraic closure [`(K<sub>v</sub>)]{\overline{K_{v}}} of K <sub>v</sub> . Let [`(K)]{\overline{K}} be the algebraic closure of K in [`(K<sub>v</sub>)]{\overline {K_{v}}}. An algebraic extension L of K, L ì [`(K)]{L\subset\overline{K}}, is said to be a v-adic maximal extension, if [`(v)] | <sub>L</sub>{\overline{v}\mid_{L}} is the only extension of v to L and L is maximal with this property. In this paper we describe some basic properties of such extensions and we consider them in connection with the v-adic spectral norm on [`(K)]{\overline{K}} and with the absolute Galois groups Gal([`(K)]/K){(\overline{K}/K)} and Gal([`(K_v)] /K_v){(\overline{K_{v}} /K_{v})}. Some other auxiliary results are given, which may be useful for other purposes.     

Measurement of the absolute branching fraction of Ds+ --> tau+ nutau decay

Using a sample of tagged D(s)(+) decays collected near the D(s)(*+/-)D(s)(-/+) peak production energy in e(+)e(-) collisions with the CLEO-c detector, we study the leptonic decay D(s)(+)-->tau(+)nu(tau) via the decay channel tau(+)-->e(+)nu(e)nu(tau). We measure B(D(s)(+)-->tau(+)nu(tau))=(6.17+/-0.71+/-0.34)%, where the first error is statistical and the second systematic. Combining this result with our measurements of D(s)(+)-->mu(+)nu(mu) and D(s)(+)-->tau(+)nu(tau) (via tau(+)-->pi(+)nu(tau)), we determine f(D(s))=(274+/-10+/-5) MeV.     

Identification of Novel Natural Inhibitors to Human 3-Phosphoglycerate Dehydrogenase (PHGDH) for Cancer Treatment

Targeting the serine biosynthesis pathway enzymes has turned up as a novel strategy for anti-cancer therapeutics. 3- Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme that catalyzes the conversion of 3-Phosphoglyceric acid (3-PG) into 3-Phosphohydroxy pyruvate (3-PPyr) in the first step of serine synthesis pathway and perform a critical role in cancer progression. PHGDH has been reported to be overexpressed in different types of cancers and emerged as a novel target for cancer therapeutics. During this study, virtual screening tools were used for the identification of inhibitors of PHGDH. A library of phenolic compounds was docked against two binding sites of PHGDH using Molegro Virtual Docker (MVD) software. Out of 169 virtually tested compounds, Salvianolic acid C and Schizotenuin F possess good binding potential to co-factor binding site of PHGDH while Salvianolic acid I and Chicoric acid were identified as the best binding compounds toward the substrate binding site of PHGDH. The top selected compounds were evaluated for different physiochemical and ADMET properties, the obtained results showed that none of these hit compounds violated the Pfizer Rule and they possess acceptable ADMET profiles. Further, a commercially available hit compound, Chicoric acid, was evaluated for its anti-cancer potential against PHGDH-expressing gastric cancer cell lines (MGC-803 and SGC-7901) as well as cell lines with low expression of PHGDH (MCF-7 and MDA-MB2-31), which demonstrated that Chicoric acid possesses selective cytotoxicity toward PHGDH expressing cancer cell lines. Thus, this study has unveiled the potential of phenolic compounds, which could serve as novel candidates for the development of PHGDH inhibitors as anti-cancer agents.     

Mechanical,Barrier, Antioxidant and Antimicrobial Properties of Alginate Films: Effect of Seaweed Powder and Plasma-Activated Water

The incorporation of natural fillers such as seaweed may potentially enhance the properties of biopolymer films. In this study, we investigated the effect of seaweed powder as a bio-filler in alginate-based films at different concentrations (10, 30, and 50%, w/w alginate) and particle sizes (100 and 200 μm) on the mechanical, barrier, antioxidant, and antimicrobial properties of alginate which are essential for food packaging applications. Initially, mechanical properties of the alginate films prepared at different temperatures were evaluated to find the optimal temperature for preparing alginate solution. The addition of seaweed powder did not have any positive effect on the mechanical properties of the alginate films. However, the barrier (water vapor transmission rate) and antioxidant properties were improved with the addition of seaweed filler regardless of concentration. In addition, selected films were prepared in plasma-activated water (PAW). The mechanical properties (tensile strength, but not elongation at break) of the films prepared with PAW improved compared to the films prepared in distilled water, while a significant decrease was observed when incorporated with the seaweed filler. The films prepared in PAW also showed improved barrier properties compared to those prepared in distilled water. The antimicrobial activity of the alginate-seaweed film-forming solution was in general more pronounced when prepared with PAW and stored at 10 °C, particularly at the highest concentration of the film-forming solution (83.3% v/v). A more pronounced inhibitory effect was observed on the Gram-positive S. aureus than on the Gram-negative E. coli, which has been attributed to the different composition and structure of the respective cell walls. This study has demonstrated the potential of seaweed filler in combination with PAW towards enhanced functionality and bioactivity of alginate films for potential food packaging applications.