A rapid and sensitive bioanalytical LC–MS/MS method for the quantitation of a novel CDK5 inhibitor 20–223 (CP668863) in plasma: Application to in vitro metabolism and plasma protein-binding studies

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (MS/MS) method was developed and validated for the quantitation of the novel CDK5 inhibitor ‘20–223' in mouse plasma. Separation of analytes was achieved by a reverse-phase ACE Excel C₁₈ column (1.7 μm, 100 × 2.1 mm) with gradient elution using 0.1% formic acid (FA) in methanol and 0.1% FA as the mobile phase. Analytes were monitored by MS/MS with an electrospray ionization source in the positive multiple reaction monitoring mode. The MS/MS response was linear over the concentration range 0.2–500 ng/mL for 20–223. The within- and between-batch precision were within the acceptable limits as per Food and Drug Administration guidelines. The validated method was successfully applied to plasma protein binding and in vitro metabolism studies. Compound 20–223 was highly bound to mouse plasma proteins (>98% bound). Utilizing mouse S9 fractions, in vitro intrinsic clearance (CL_int) was 24.68 ± 0.99 μL/min/mg protein. A total of 12 phase I and II metabolites were identified with hydroxylation found to be the major metabolic pathway. The validate method required a low sample volume, was linear from 0.2 to 500 ng/mL, and had acceptable accuracy and precision.     

Palladium nanoparticles‐decorated triethanolammonium chloride ionic liquid‐modified TiO2 nanoparticles (TiO2/IL‐Pd): A highly active and recoverable catalyst for Suzuki–Miyaura cross‐coupling reaction in aqueous medium

In this work, an easily obtained procedure was successfully implemented to prepare novel palladium nanoparticles decorated on triethanolammonium chloride ionic liquid‐functionalized TiO₂ nanoparticles [TiO₂/IL‐Pd]. Different methods were carried out for characterizations of the synthesized nanocatalyst (HR‐TEM, XPS, XRD, FE‐SEM, EDX, FT‐IR and ICP). TiO₂/IL‐Pd indicated good catalytic activity for the Suzuki–Miyaura cross‐coupling reaction of arylboronic acid with different aryl halides in aqueous media at ambient temperature. The recycled catalyst was investigated with ICP to amount of Pd leaching after 6 times that had diminished slightly, Thus, was confirmed that the nanocatalyst has a good sustainability for C–C Suzuki–Miyaura coupling reaction. The catalyst can be conveniently separated by filtration of the reaction mixture and reused for 6 times without significant loss of its activity. It supplies an environmentally benign alternative path to the existing protocols for the Suzuki–Miyaura reaction.     

The martingale problem for a class of nonlocal operators of diagonal type

We consider systems of stochastic differential equations of the form $$\begin{array}{c}\hfill d{X}_t^i=\sum _{j=1}^d{A}_{ij}\left(X_{t?}\right)d{Z}_t^j\end{array}$$ for $i=1,?,d$ with continuous, bounded and non‐degenerate coefficients. Here $Z_t^1,?,Z_t^d$ are independent one‐dimensional stable processes with ${\alpha }_1,?,{\alpha }_d\in (0,2)$. In this article we research on uniqueness of weak solutions to such systems by studying the corresponding martingale problem. We prove the uniqueness of weak solutions in the case of diagonal coefficient matrices.     

Regular characters of classical groups over complete discrete valuation rings

Let $\mathfrak{o}$ be a complete discrete valuation ring with finite residue field $\mathsf{k}$ of odd characteristic, and let G be a symplectic or special orthogonal group scheme over $\mathfrak{o}$. For any $?\in \mathbb{N}$ let $G^{?}$ denote the ?-th principal congruence subgroup of $\mathbf{G}(\mathfrak{o})$. An irreducible character of the group $\mathbf{G}(\mathfrak{o})$ is said to be regular if it is trivial on a subgroup $G^{?+1}$ for some ?, and if its restriction to $G^{?}/G^{?+1}?\mathrm{Lie}(\mathbf{G})(\mathsf{k})$ consists of characters of minimal $\mathbf{G}({\mathsf{k}}^{\mathrm{alg}})$-stabilizer dimension. In the present paper we consider the regular characters of such classical groups over $\mathfrak{o}$, and construct and enumerate all regular characters of $\mathbf{G}(\mathfrak{o})$, when the characteristic of $\mathsf{k}$ is greater than two. As a result, we compute the regular part of their representation zeta function.     

Weighted estimates for the multilinear maximal function on the upper half‐spaces

For a general dyadic grid, we give a Calderón–Zygmund type decomposition, which is the principle fact about the multilinear maximal function on the upper half‐spaces. Using the decomposition, we study the boundedness of . We obtain a natural extension to the multilinear setting of Muckenhoupt's weak‐type characterization. We also partially obtain characterizations of Muckenhoupt's strong‐type inequalities with one weight. Assuming the reverse Hölder's condition, we get a multilinear analogue of Sawyer's two weight theorem. Moreover, we also get Hytönen–Pérez type weighted estimates.     

Mechanistic studies on the reaction between glutathionylcobalamin and selenocysteine

Abstract

The reaction between glutathionylcobalamin (GSCbl), a complex of Co(III)-cobalamin with glutathione, and selenocysteine (Sec) was investigated using ultraviolet-visible (UV–vis) spectroscopy. The interaction results in the formation of cob(II)alamin and proceeds via two pathways: (i) a rapid formation of complex between GSCbl and Sec followed by the rate-determining substitution of glutathionyl-ligand by Sec and rapid electron-transfer from Se-atom to Co(III)-ion and (ii) a nucleophilic attack of Co(III)-S bond by Sec.     

BiVO4/TiO2 heterojunction with rich oxygen vacancies for enhanced electrocatalytic nitrogen reduction reaction

The large-scale production of ammonia mainly depends on the Haber–Bosch process, which will lead to the problems of high energy consumption and carbon dioxide emission. Electrochemical nitrogen fixation is considered to be an environmental friendly and sustainable process, but its efficiency largely depends on the activity and stability of the catalyst. Therefore, it is imperative to develop highefficient electrocatalysts in the field of nitrogen reduction reaction (NRR). In this paper, we developed a BiVO₄/TiO₂ nanotube (BiVO₄/TNT) heterojunction composite with rich oxygen vacancies as an electrocatalytic NRR catalyst. The heterojunction interface and oxygen vacancy of BiVO₄/TNT can be the active site of N₂ dynamic activation and proton transition. The synergistic effect of TiO₂ and BiVO₄ shortens the proton transport path and reduces the over potential of chemical reaction. BiVO₄/TNT has high ammonia yield of 8.54 μg·h⁻¹·cm⁻² and high Faraday efficiency of 7.70% in −0.8 V vs. RHE in 0.1 M Na₂SO₄ solution.