Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.     

Functional Groups Assisted Tunable Dielectric Permittivity of Guest-Free Zn-Based Coordination Polymers for Gate Dielectrics

The dielectric properties of coordination polymers has been a topic of recent interest, but the role of different functional groups on the dielectric properties of these polymers has not yet been fully addressed. Herein, the effects of electron-donating (R=NH₂) and electron-withdrawing (R=NO₂) groups on the dielectric behavior of such materials were investigated for two thermally stable and guest-free Zn-based coordination polymers, [Zn(L₁)(L₂)]_n ( 1 ) and [Zn(L₁)(L₃)]_n ( 2 ) [L₁=2-(2-pyridyl) benzimidazole (Pbim), L₂=5-aminoisophthalate (Aip), and L₃=5-nitroisophthalate (Nip)]. The results of dielectric studies of 1 revealed that it possesses a high dielectric constant (κ=65.5 at 1 kHz), while compound 2 displayed an even higher dielectric constant (κ=110.3 at 1 kHz). The electron donating and withdrawing effects of the NH₂ and NO₂ substituents induce changes in the polarity of the polymers, which is due to the inductive effect from the aryl ring for both NO₂ and NH₂. Theoretical results from density functional theory (DFT) calculations, which also support the experimental findings, show that both compounds have a distinct electronic behavior with diverse wide bandgaps. The significance of the current work is to provide information about the structure-dielectric property relationships. So, this study promises to pave the way for further research on the effects of different functional groups on coordination polymers on their dielectric properties.     

One-pot Synthesis,Crystal Structures and Antimicrobial Activities of Two New 1,4-Disubstituted 1,2,3-Triazole-4-Carboxylates

Two new 1,4-disubstituted 1,2,3-triazoles-4-carboxylates were synthesized via click reaction. Compound 1a was synthesized by the interaction of 6-nitro-tetrazolo[1.5-a]-pyridine with ethyl propynoate at room temperature in the presence of Cu(OAc)2 as a catalyst and THF as solvent. Compound 1b was also synthesized by the same manner except that tert-butyl propionate, instead of ethyl propynoate, was used. The compounds were characterized by IR, 1H-NMR, 13C-NMR and single-crystal X-ray diffraction analysis. Compound 1a(C10H9N5O4) crystallizes in the triclinic system, space group P1 with a = 5.0894(9), b = 8.9834(13), c = 13.089(2) ?, α= 83.041(7), β= 80.256(7), γ=87.296(8)°, V = 585.24(16)?3, Z = 2, Mr = 263.22, crystal size(mm) = 0.37 × 0.20 ×0.18,(I 2σ(I)) = 8557, 2493, 1229, Rint = 0.057. Compound 1b(C12H13N5O4) crystallizes in the monoclinic system, space group P21/c with a = 6.8854(5), b = 21.783(2), c = 9.3986(8) ?,β = 93.239(4)°, V = 1407.4(2)?3, Z = 4, Mr = 291.27, crystal size(mm) = 0.38 × 0.22 × 0.20,(I 2σ(I)) = 11842, 3172, 1866, Rint = 0.047. Antimicrobial assay results showed that the title compounds display excellent activities to different bacterial and fungal strains.     

Designing spirobifullerene core based three-dimensional cross shape acceptor materials with promising photovoltaic properties for high-efficiency organic solar cells

The development of organic electron acceptor materials is one of the key factors for realizing high-performance organic solar cells (OSCs). Nonfullerene electron acceptors, compared to traditional fullerene acceptor materials, have gained much impetus owing to their better optoelectronic tunabilities and lower cost, as well as higher stability. Therefore, 5 three-dimensional (3D) cross-shaped acceptor materials having a spirobifullerene core flanked with 2,1,3-benzothiadiazole are designed from a recently synthesized highly efficient acceptor molecule SF(BR) ₄ and are investigated in detail with regard to their use as acceptor molecules in OSCs. The density functional theory (DFT) and time-dependent DFT (TDDFT) calculations have been performed for the estimation of frontier molecular orbital (FMO) analysis, density of states analysis, reorganization energies of electron and hole, dipole moment, open-circuit voltage, photo-physical characteristics, and transition density matrix analysis. In addition, the structure-property relationship is studied, and the influence of end-capped acceptor modifications on photovoltaic, photo-physical, and electronic properties of newly selected molecules ( H1-H5 ) is calculated and compared with reference ( R ) acceptor molecule SF(BR) ₄ . The structural tailoring at terminals was found to effectively tune the FMO band gap, energy levels, absorption spectra, open-circuit voltage, reorganization energy, and binding energy value in selected molecules H1 to H5 . The 3D cross-shaped molecules H1 to H5 suppress the intermolecular aggregation in PTB7-Th blend, which leads to high efficiency of acceptor material H1 to H5 in OSCs. Consequently, better optoelectronic properties are achieved from designed molecules H1 to H5 . It is proposed that the conceptualized molecules are superior than highly efficient spirobifullerene core-based SF(BR) ₄ acceptor molecules and, thus, are recommended to experiments for future developments of highly efficient solar cells.     

Barium(II)–2,4‐dinitrophenolate–18‐crown‐6 at 183 K

The title compound, bis(2,4‐dinitrophenolato‐κ²O,O′)(1,4,7,10,13,16‐hexaoxadecane‐κ⁶O)barium(II), [Ba(C₆H₃N₂O₅)₂(C₁₂H₂₄O₆)], is a 1:1 complex of barium(II)–2,4‐di­nitro­phenolate and 1,4,7,10,13,16‐hexaoxa­cyclo­octa­decane (18‐crown‐6). Its structure is located on a crystallographic inversion centre. The temperature dependence of the crystal structure has been studied. The monoclinic β angle of the P2₁/­n space group increases with increasing temperature. The packing structure of the complex is stabilized by intermolecular C—H?O interactions.     

1‐Acetyl‐3′‐(4‐bromophenyl)‐3′‐chlorospiro[3H‐indole‐3,2′‐oxetan]‐2(1H)‐one

In the title compound, C₁₈H₁₃BrClNO₃, the heterocyclic ring of the indole is distorted from planarity towards an envelope conformation. The orientations of the indole, oxetane, chloro and bromo­phenyl substituents are conditioned by the sp³ states of the spiro‐junction and the Cl‐attached C atoms.     

Di‐2‐pyridyl ketone N4,N4‐(butane‐1,4‐diyl)thiosemicarbazone

The title compound, C₁₆H₁₇N₅S, is in the thione form and crystallizes with two independent mol­ecules in the asymmetric unit. In both mol­ecules, the penta­methyl­ene­imine five‐membered ring adopts an envelope conformation, and in one of the molecules this ring shows positional disorder. The thione S and hydrazine N atoms are in the Z configuration with respect to the C—N bond.     

Bis[1,1′‐bis(diphenylphosphino)ferrocenium] hexadecachlorotetraantimony(III) ethanol solvate

In the title compound, [Fe(C₁₇H₁₄P)₂]₂[Sb₄Cl₁₆]·C₂H₆O, the Fe atoms lie on inversion centres and the pairs of cyclopentadienyl rings are consequently in a fully staggered conformation. The centrosymmetric anionic clusters formed by [Sb₄Cl₁₆]^4? are surrounded by the cations and are held together by weak C—H?Cl interactions. These formations stack along the a axis to form columns, and the columns are interconnected by another weak C—H?Cl interaction along the b axis.     

Bis­(ethyl­enedi­amine)copper(II) bis(O,O′‐diethyl di­thio­phosphate)

In the structure of the title compound, [Cu^II­(en)₂][(EtO)₂P(S)S]₂ (en is ethyl­ene­di­amine) or [Cu(C₂H₈N₂)₂](C₄H₁₀O₂PS₂)₂, the Cu atom lies on a center of inversion and is coordinated in a slightly distorted square coordination geometry by four N atoms from two ethyl­enedi­amine mol­ecules. The diethyl di­thio­phosphate moieties, (EtO)₂P(S)S^?, act as counter‐anions.     

Aminopropylcellulose,synthesis and derivatization

The preparation of 3-aminopropylcellulose from cyanoethylcellulose is readily achieved. Reduction of the cyano groups with borane-dimethyl sulfide in tetrahydrofuran or a borane-tetrahy-drofuran complex proceeds quantitatively in 3 h to a corresponding 3-aminopropylcellulose. The presence of primary amine functions is confirmed by spectroscopy and a positive ninhydrin test; the concentration of amino substituents, as ascertained by titration, ranged from 1.2 to 6.4 meq/g. Because the derivatives are neither soluble nor excessively swollen in water, applications as ion-exchange resins or chromatographic supports can be envisioned. Treatment of 3-aminopropyl-cellulose with acetyl chloride, phenyl isocyanate, or p-toluenesulfonyl isocyanate produced 3-acetamido-, 3-(N′-phenyluredo)-, or 3-(N′-p-toluenesulfonyluredo)-N-propylcellulose. Alkylation with methyl chloride yielded a water-soluble quaternary ammonium salt.