Characterization of In Vivo Metabolites of a Potential Anti-obesity Compound,the 3-Methyl-1H-Purine-2,6-Dione Derivative C-11, Employing Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry

C-11 (2-((7-Ethyl-3-methyl-8-(4-(2-(methyl(pyridin-2-yl)-amino)-ethoxy)phenyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)methyl)benzonitrile-one hydrochloride), which is based on the structure of rosiglitazone, was first synthesized in our laboratory and shown to be a promising anti-obesity drug candidate in our previous pharmacological study. Considering the importance of metabolic fate in vivo in the further development of drug candidates during early drug discovery, it is essential to characterize the metabolism of C-11 in vivo. In this work, a method based on ultra-high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) was successfully developed to investigate the in vivo metabolic profile of C-11 in rats. Rat urine, feces, and plasma samples were collected from male Sprague–Dawley rats after intravenous administration of C-11 in a single dose of 30 mg kg⁻¹ body weight. Besides the parent drug, a total of 25 metabolites (including 18 phase I and 7 phase II metabolites) were detected and tentatively identified by comparing their mass spectrometry profiles with those of C-11. This enabled the metabolic pathways of C-11 to be proposed for the first time. Our results revealed that N-depyridinylation, N-demethylation, hydroxylation, glucuronidation, and sulfate conjugation are the predominant metabolic pathways of C-11 in rats. The present study provides systematic information on the metabolism of C-11 in vivo, which should lead to a better understanding of its safety and mechanism of action.

     

Effect of solvent on directional drift in Brownian motion of particle/molecule with broken symmetry

The directional drifting of particles/molecules with broken symmetry has received increasing attention. Through molecular dynamics simulations, we investigate the effects of various solvents on the time-dependent directional drifting of a particle with broken symmetry. Our simulations show that the distance of directional drift of the asymmetrical particle is reduced while the ratio of the drift to the mean displacement of the particle is enhanced with increasing mass, size, and interaction strength of the solvent atoms in a short time range. Among the parameters considered, solvent atom size is a particularly influential factor for enhancing the directional drift of asymmetrical particles, while the effects of the interaction strength and the mass of the solvent atoms are relatively weaker. These findings are of great importance to the understanding and control of the Brownian motion of particles in various physical, chemical, and biological processes within finite time spans.     

Patterned solutions of a homogenous diffusive predator-prey system of Holling type-III

Acta Mathematicae Applicatae Sinica, English Series - In this paper, a diffusive predator-prey system of Holling type functional III is considered. For one hand, we considered the possibility of...     

Relationship between liquid crystalline phase stability and ingredient composition in liquid crystal oil–water emulsion

In this study, we postulated that the optical retardation magnitude could be used to evaluate the stability of the LC phase through the Mueller matrix polarimeter method in LC emulsion. In addition, we found that the increase of cetearyl alcohol concentration induced the more periodic dense lattice structure in crystalline phase of LC lamellae and the sorbitan olivate was relatively more responsible for higher ordering in LC phase compared to C12–20 alkyl glucoside in terms of molecular parallel packing on the basis of the optical retardation magnitude. Furthermore, it was confirmed that the LC emulsion had higher skin barrier function owing to lower TEWL and higher reflectance than ordinary emulsion on human skin and maintained a uniform phase without phase separation for 8 weeks.     

A New Emissive Chalcone-Based Chemosensor Armed by Coumarin and Naphthol with Fluorescence “Turn-on” Properties for Selective Detection of F<Superscript>−</Superscript> Ions

A new chalcone-based probe containing coumarin and naphthol at both ends has been synthesized via aldol condensation. The uniqueness of the newly derived probe can be ascribed to the presence of naphthol and coumarin units acting as binding site and signaling element, respectively. The fluorogenic behaviors toward various anions were investigated. The probe was characterized by various spectroscopic techniques and the in-depth study led to show excellent selectivity and sensitivity for fluoride ions. The hydrogen bonding thus formed with fluoride anion provides remarkable fluorometric responses. The interactions of the probe with fluoride ions were determined by fluorescence, FT-IR and NMR spectroscopic techniques. The exploratory studies by fluorescent spectral changes augur well for the naked-eye sensing applications.     

An Atomically Precise Au10Ag2 Nanocluster with Red–Near‐IR Dual Emission

A red–near‐IR dual‐emissive nanocluster with the composition [Au₁₀Ag₂(2‐py?C≡C)₃(dppy)₆](BF₄)₅ ( 1 ; 2‐py?C≡C is 2‐pyridylethynyl, dppy=2‐pyridyldiphenylphosphine) has been synthesized. Single‐crystal X‐ray structural analysis reveals that 1 has a trigonal bipyramidal Au₁₀Ag₂ core that contains a planar Au₄(2‐py?C≡C)₃ unit sandwiched by two Au₃Ag(dppy)₃ motifs. Cluster 1 shows intense red–NIR dual emission in solution. The visible emission originates from metal‐to‐ligand charge transfer (MLCT) from silver atoms to phosphine ligands in the Au₃Ag(dppy)₃ motifs, and the intense NIR emission is associated with the participation of 2‐pyridylethynyl in the frontier orbitals of the cluster, which is confirmed by a time‐dependent density functional theory (TD‐DFT) calculation.     

Thermal and optical properties of highly fluorinated copolymers of methacrylates

Copolymers of pentafluorophenylhexafluoroisopropyl methacrylate (FPPMA) with trifluoroethyl methacrylate (TFEMA) were prepared in THF solution and in bulk using azobisisobutyronitrile as a free radical initiator. The monomer reactivity ratios of TFEMA (M₁) and FPPMA (M₂) were calculated as r₁ = 0.55 and r₂ = 0.07. The refractive indices of poly(TFEMA) and poly(FPPMA) are very similar as 1.435 and 1.430, respectively, at 532 nm, and the copolymer films were transparent. The glass transition temperatures (T_g) of the copolymers were in the range of 80–90°C and showed a negative deviation from the Gordon–Taylor equation. The thermal decomposition temperature (T_d) was increased with the content of FPPMA in copolymers. Low water absorption for 1:1 FPPMA/TFEMA copolymer was detected. Copolymers of FPPMA with hexafluoroisopropyl methacrylate (HFPMA) were also prepared. The monomer reactivity ratios of HFPMA (M₁) and FPPMA (M₂) were calculated as r₁ = 0.43 and r₂ = 0.10. The T_gs of the copolymers were in the range of 88–95°C and showed also a negative deviation from the Gordon–Taylor equation. T_g and T_d of the copolymers were increased with the content of FPPMA. The refractive index of poly(HFPMA) (1.384 at 532 nm) is much lower than that of FPPMA homopolymer, but copolymer films obtained were clear and transparent. Copyright © 2013 John Wiley & Sons, Ltd.