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1.
In order to investigate SAR regarding glucose moiety in novel C-aryl glucoside SGLT2 inhibitors containing a thiazole motif, a series of chemical modifications on glucose was conducted to explore potential utility as a suitable replacement of glucose per se. Among the compounds prepared, deshydroxy 29 (IC50 = 7.01 nM) demonstrated the best in vitro inhibitory activity against SGLT2 in this series to date. But, none of the compounds were better than the parent molecule 5 (IC50 = 1.75 nM).  相似文献   

2.
A series of imidazolium chlorides as ligand precursors, L · HCl (L = (1-R)-(3-diphenylphosphanylethyl)-imidazol-2-ylidene; R = aryl, benzyl, naphthylmethyl), for the phosphine-functionalized N-heterocyclic carbene (NHC), L, were prepared by a convenient synthetic procedure of reacting 1,2-dichloroethane with appropriate N-substituted imidazoles to give (β-chloroethyl)imidazolium chlorides, which were subsequently reacted with HPPh2 producing L · HCl in good yield. Palladium complexes of L, PdLCl2 (4), were prepared by a one pot reaction of PdCl2, sodium acetate, and L · HCl in DMSO. Complexes 4b (R = naphthylmethyl) and 4e (R = m-methoxybenzyl) were characterized by X-ray crystallography. Catalytic studies have shown that the palladium complexes are efficient in Suzuki coupling reactions of aryl bromides with phenylboronic acid.  相似文献   

3.
In this work, we demonstrated the regulation of glucose transporters by hypoxia inducible factor-1α (HIF-1α) activation in renal epithelial cells. LLC-PK1 monolayers were incubated for 1, 3, 6, or 12 h with 0% or 5% O2 or 300 μm cobalt (CoCl2). We evaluated the effects of hypoxia on the mRNA and protein expression of HIF-1α and of the glucose transporters SGLT1, SGLT2, and GLUT1. The data showed an increase in HIF-1α mRNA and protein expression under the three evaluated conditions (p < 0.05 versus t = 0). An increase in GLUT1 mRNA (12 h) and protein expression (at 3, 6, and 12 h) was observed (p < 0.05 versus t = 0). SGLT1 and SGLT2 mRNA and protein expression decreased under the three evaluated conditions (p < 0.05 versus t = 0). In conclusion, our results suggest a clear decrease in the expression of the glucose transporters SGLT1 and SGLT2 under hypoxic conditions which implies a possible correlation with increased expression of HIF-1α.  相似文献   

4.
Hybrid density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations have been carried out for ozone-water clusters O3(H2O)n (n = 1-4) in order to obtain hydration effects on the absorption spectrum of ozone. The first water molecule in n = 1 is bound to the ozone molecule by an oxygen orientation form in which the oxygen atom of H2O orients the central oxygen atom of O3. In n = 2, the water dimer is bound to O3 and then the cyclic structure is formed as the most stable structure. For n = 3 (or n = 4), the cyclic water trimer (or tetramer) is bound by a hydrogen bond to the ozone molecule. The TD-DFT calculations of O3(H2O)n (n = 0-4) show that the first and second excitation energies of O3 are blue-shifted by the interaction with the water clusters. The magnitude of the spectral shift is largest in n = 2, and the shifts of the excitation energies are +0.07 eV for S1 and +0.13 eV for S2 states. In addition to the spectral shifts (S1 and S2 states), it is suggested that a charge-transfer band is appeared as a low-lying excited state above the S1 and S2 states. The origin of the spectrum shifts was discussed on the basis of theoretical results.  相似文献   

5.
Knoevenagel condensation of 4-(dimethylamino)benzaldehyde with 4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (bpcd) gives the donor-acceptor ligand 2-(4-dimethylaminobenzylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (dbpcd). The reaction of dbpcd with PtCl2(cod) affords the platinum(II) complex PtCl2(dbpcd) in high yield. The free dbpcd ligand and PtCl2(dbpcd) have been isolated and fully characterized in solution by IR and NMR spectroscopies, and the solid-state structure of PtCl2(dbpcd) determined by X-ray diffraction analysis. PtCl2(dbpcd), as the 1.5CH2Cl2 solvate, crystallizes in the triclinic space group , a = 11.7412(7) Å, b = 12.0486(7) Å, c = 14.4781(9) Å, α = 82.866(1), β = 75.049(1), γ = 83.905(1), V = 1957.6(2) Å3, Z = 2, and Dcalc = 1.678 mg/m3, R = 0.0291 and wR2 = 0.0723 for 8315 reflections with I > 2σ(I). The molecular structure of PtCl2(dbpcd)·1.5CH2Cl2 consists of a square-planar platinum architecture containing two chlorines and the ancillary dbpcd diphosphine ligand. The redox properties of the dbpcd ligand and PtCl2(dbpcd) have been explored by cyclic voltammetry, and these data are discussed with respect to extended Hückel MO calculations.  相似文献   

6.
To investigate the mechanism of interaction of gramicidin S-like antimicrobial peptides with biological membranes, a series of five decameric cyclic cationic β-sheet-β-turn peptides with all possible combinations of aromatic D-amino acids, Cyclo(Val-Lys-Leu-D-Ar1-Pro-Val-Lys-Leu-D-Ar2-Pro) (Ar ≡ Phe, Tyr, Trp), were synthesized. Conformations of these cyclic peptides were comparable in aqueous solutions and lipid vesicles. Isothermal titration calorimetry measurements revealed entropy-driven binding of cyclic peptides to POPC and POPE/POPG lipid vesicles. Binding of peptides to both vesicle systems was endothermic—exceptions were peptides containing the Trp-Trp and Tyr-Trp pairs with exothermic binding to POPC vesicles. Application of one- and two-site binding (partitioning) models to binding isotherms of exothermic and endothermic binding processes, respectively, resulted in determination of peptide-lipid membrane binding constants (Kb). The Kb1 and Kb2 values for endothermic two-step binding processes corresponded to high and low binding affinities (Kb1 ≥ 100 Kb2). Conformational change of cyclic peptides in transferring from buffer to lipid bilayer surfaces was estimated using fluorescence resonance energy transfer between the Tyr-Trp pair in one of the peptide constructs. The cyclic peptide conformation expands upon adsorption on lipid bilayer surface and interacts more deeply with the outer monolayer causing bilayer deformation, which may lead to formation of nonspecific transient peptide-lipid porelike zones causing membrane lysis.  相似文献   

7.
The reactions of metal(II) chlorides and bromides with 8-methylquinoline (8-mequin) in neutral and acidic solutions were investigated. The reaction with ZnCl2, ZnBr2, CoCl2, CoBr2, CuCl2 or CuBr2 with the appropriate HX in water or aqueous ethanol gave complexes of the formula (8-mequin)2MX4 (1, M = Cu, X = Cl; 2, M = Cu, X = Br; 3, M = Co, X = Cl; 4, M = Co, X = Br) or (8-mequin)2ZnX4·nH2O (5, X = Cl, n = 0; 6, X = Br, n = 0; 7, X = Cl, n = 1; 8, X = Br, n = 1). Crystals of 1, 2 and 4-8 suitable for single crystal X-ray diffraction were obtained and the structures reported. Compounds 1 and 2 crystallize in the monoclinic space group C2/c, while 4-8 crystallize in the triclinic space group, . Variable temperature magnetic susceptibility data indicate very weak interactions for the copper compounds 1 and 2, while the magnetic behavior of 3 and 4 is dominated by single ion anisotropy, with weaker antiferromagnetic interactions.  相似文献   

8.
The reaction between a new amino dicarboxylic ligand N-(2-carboxybenzomethyl)-β-alanine (H2cbal) obtained by reducing the Schiff base N-(2-carboxybenzoimine)-β-alanine and copper(II) perchlorate afforded a novel tetracopper(II) complex. This tetracopper(II) complex shows unusual structure and novel core topology. The electrochemical study of the complex using cyclic voltammetrry in acetonitrile indicated the presence of a reversible one-electron reduction and two irreversible reductions at higher potentials. The EPR studies of the complex and one electron reduce form of the complex in acetonitrile at 115 K showed an axial signal with g > g > 2.0 and an isotropic signal, respectively.  相似文献   

9.
Two new TTF-based donors that are dithiolene ligand precursors, 3-{5-[(2-cyanoethyl)thio]-2-(5,6-dihydrothieno[2,3-d][1,3]dithiol-2-ylidene-1,3-dithiol-4-yl)thio}propanenitrile, dtdt (1) and 3-({5-[(2-cyanoethyl)thio]-2-thieno[2,3-d][1,3]dithiol-2-ylidene-1,3-dithiol-4-yl)thio}propanenitrile, α-tdt (2), were synthesized and characterized. The electrochemical properties of these compounds were studied by cyclic voltammetry (CV) in acetonitrile. Compound 1 shows two reversible oxidation process at 1E1/2 = 0.639 V and 2E1/2 = 0.997 V versus Ag/AgCl. This same processes occurs at 1E1/2 = 0.612 V and 2E1/2 = 0.906 V in the case of 2. The crystal structures confirm the ability of these molecules to establish interactions with their neighbours through the peripheral sulfur atoms.  相似文献   

10.
The title ligand, N-(2-hydroxyphenyl)methyl-bis-(2-pyridylmethyl)amine, was prepared via a condensation-reduction synthetic route. The compounds, CuCl(C19H19N3O) and [CuBr(C19H19N3O)]+Br · 3H2O, were readily synthesized from the reaction of CuCl or CuBr2 and the ligand in acetonitrile. The title copper(I) compound is an O-H ? Cl hydrogen-bonded linear chain of tetrahedrally coordinated copper centers, and the title copper(II) compound exists as two strongly tetragonally distorted dibromide bridged metal cations in a dimer with the phenol hydroxyl groups weakly bound in a trans-fashion to one of the bridging bromides. In the copper(I) complex the phenoxy group acts only as a hydrogen bond donor, whereas in the copper(II) complex it acts both as a ligand and a hydrogen bond donor.  相似文献   

11.
The reaction of the non-symmetric phosphorus ylides, Ph2P(CH2)nPPh2C(H)C(O)PhR [Y1-Y4: n = 1, R = Cl, Br, NO2, OCH3 and Y5-Y8: n = 2, R = Cl, Br, NO, OCH3] with dichloro(1,5-cyclooctadiene)palladium(II) in dichloromethane under mild conditions afford the monomeric P-C chelated complexes, [(Y)PdCl2] (Y = Y1-Y8). These complexes were fully characterized by elemental analysis and spectroscopic techniques such as IR, 1H, 31P, and 13C NMR. In addition, the identity of complexes [(Y5)PdCl2] (1b) and [(Y8)PdCl2] (4b) was unequivocally determined by single crystal X-diffraction techniques, both structures consisting of six-membered rings formed by coordination of the ligands through the phosphine group and the ylidic carbon atom to the metal center. The coordination geometry around the Pd atoms in both these complexes be defined as slightly distorted square planar. Furthermore, their electrochemical behavior was also investigated by cyclic voltammeters, thus the cyclic voltammetry of complex [(Y1)PdCl2], in dichloromethane solution with Pt electrode, shows that the redox reaction of the pair Pd(II)/Pd(0) is irreversible with the cathodic peak potential at −1.08 V versus Ag wire.  相似文献   

12.
A new polyoxotungstate formed by Wells-Dawson clusters and copper(II) complexes, [{Cu(enMe)2(H2O)}{Cu(enMe)2}3P2W18O62] · nH2O (enMe = 1,2-diaminopropane, n = 0.81) has been synthesized under hydrothermal conditions. Single-crystal X-ray diffraction revealed that one terminal and three bridging oxygen atoms of the Wells-Dawson cluster in the title compound are coordinated to copper(II) atoms, and forming a unique tetrasupporting polyoxometalate structure. Its cyclic voltammetric behavior in aqueous electrolyte demonstrated that its modified carbon paste electrode has a good stability. It was exhibited that the compound has catalytic activity in epoxidation of maleic anhydride.  相似文献   

13.
The redox-active doubly bridged species [{Mo(NO)(TpMe2)Q}2] [TpMe2 = tris(3,5-dimethylpyrazol-1-yl)hydroborate, Q = O(CH2)nO, n = 3, 5, or OCH2(CF2)n−2CH2O, n = 5, 6], and a chelate complex [Mo(NO)-(TpMe2)O(CH2)5O] were prepared and characterised by elemental and mass analyses, 1H NMR and IR spectroscopy. The bimetallic species with C3, C5, and C5(F) bridges exhibit two well-resolved reduction processes in their cyclic voltammograms (ΔE1/2 values of 290, 170, and 170 mV, respectively). These results indicate that the presence of the second bridge increases the extent of electrochemical interactions (by ca. 90-130 mV) in comparison with their singly bridged analogues. All non-fluorinated and the chelate species were catalytically active in cathodic reduction of chloroform.  相似文献   

14.
2-Phenylquinoline-4-carboylhydrazide (HL), and its novel nickel(II), zinc(II) complexes [M(HL)2(L)]·2H2O·NO3 (M = Ni (1), M = Zn (2)), have been synthesized and characterized by elemental analysis, molar conductivity, and IR spectra. The crystal structure of [Ni(HL)2(L)]·2H2O·NO3 obtained from ethanol solution was determined by X-ray diffraction analysis, crystallized in the rhombohedral system, space group , Z = 18, a = 31.913(3) Å, b = 31.913(3) Å, c = 27.709(2) Å, α = 90°, β = 90°, γ = 120°, R1 = 0.0647. The interactions of the complexes and the ligand with calf thymus DNA had been investigated using UV-Vis spectra, fluorescent spectra, CD (circular dichroism) spectra, CV (cyclic voltammetry) and viscosity measurements. These compounds were tested against MFC (mouse forestomach carcinoma) cell lines. The complex 1 showed significant cytotoxic activity against MFC cell lines. The cleavage reaction on plasmid DNA has been monitored by agarose gel electrophoresis. Results suggest that the two complexes bound to DNA via a groove binding mode and the complexes can cleave pBR322 DNA.  相似文献   

15.
Rhodium(III) complexes of 1,2-naphthoquinone-1-oxime (1-nqo) [Rh(1-nqo)L2Cl2] 1-3 [1, L = 4-methylpyridine (mpy); 2, L = 4-phenylpyridine (ppy); 3, L = 4-acetylpyridine (apy)] were prepared. The structure of complex 1 is analyzed by single crystal X-ray crystallography. All of the complexes were characterized by mass spectrometry, 1H-1H COSY NMR and FT-IR. UV-Vis absorption spectroscopy and cyclic voltammetry were employed to investigate the electronic transition behaviors of the complexes. The complexes displayed irreversible metal-localized two-electron reductions from RhIII to RhI on the cyclic voltammogram. While the low-energy absorptions at λmax of 488-490 nm on the UV-Vis spectra of the complexes were related to metal to 1-nqo ligand charge transfer [MLCT, dπ(Rh) → π∗(1-nqo)] and chloride to 1-nqo ligand charge transfer [LLCT, pπ(Cl) → π∗(1-nqo)] based on the theoretical calculations using time-dependent density functional theory (TD-DFT).  相似文献   

16.
Novel calix[4]pyrrole bearing vic-dioxime ligand (LH2) of the general formula, R1R2C2N2O2H2 (where, R1 = C6H5- and R2 = C39H50N5-) has been synthesized by the reaction of anti-chlorophenylglyoxime with 3-aminophenylcalix[4]pyrrole at room temperature. The mononuclear Cu(II), Ni(II) and Co(II)complexes of this vic-dioxime ligand were prepared and their structures were confirmed by elemental analysis, FT-IR, TGA and magnetic susceptibility measurements; the HMBC, DEPT, 1H and 13C NMR spectra of the LH2 ligand were also reported. The electrochemical property of the complexes was investigated in DMSO by cyclic voltammetry at 200 mV s−1 scan rate. The cyclic voltammetric measurements clearly indicated that Co(LH)2·2H2O complex differs from the Ni(LH)2 and Cu(LH)2 complexes upon the exhibition of quasi-reversible one-electron transfer reduction process in the negative region instead of an irreversible process.  相似文献   

17.
The coordination behaviour of ferrocenylthiosemicarbazone was investigated in a trinuclear [Ni(Fctsc)2] complex. The structure of the complex has been studied by X-ray crystallography. The complex crystallizes in rhombohedral space group with six molecules per unit cell has the dimensions of a = 28.8042(2) Å, b = 28.8042(2) Å and c = 19.5131(3) Å, α = 90°, β = 90°, γ = 120°. The electronic communication between the metal centers has been studied by cyclic voltammetry.  相似文献   

18.
The ruthenium complexes, trans-[Ru(phen-NH-phen)(eina)2](PF6)2 and trans-[Ru(phen-NH-phen)(ina)2](PF6)2 where phen-NH-phen = N,N-bis(1,10-phenanthroline-2-yl)amine, ina = isonicotinic acid and eina = ethyl isonicotinate, have been synthesized and characterized by 1H NMR, elemental analysis, and IR spectroscopy. The compounds were non-emissive at room temperature, but displayed intense photoluminescence in 4:1 ethanol/methanol glasses at 77 K with corrected emission maximum at 570-580 nm. A quasi-reversible wave observed in cyclic voltammetry experiments was assigned to the RuIII/II couple, (trans-[Ru(phen-NH-phen)(eina)2)3+/2+ = +1.22 V versus Ag/AgCl. The trans-[Ru(phen-NH-phen)(ina)2](PF6)2 compound was found to bind to nanocrystalline TiO2 thin films from acetonitrile solution. Pulsed 532 nm excitation of trans-[Ru(phen-NH-phen)(ina)2](PF6)2 anchored to mesoporous nanocrystalline TiO2 thin films resulted in an absorption difference spectra consistent with the formation of an interfacial charge separated state trans-[RuIII (phen-NH-phen)(ina)2]+/TiO2 (e). The formation of this state could not be time resolved, consistent with rapid excited state injection into the TiO2, kinj > 108 s−1. Comparative measurements with a thin film actinometer yielded an injection quantum yield (?inj) of 0.8. Charge recombination required milliseconds for completion and followed a bi-second-order equal concentration kinetic model with k1 = 1.0 × 108 s−1, and k2 = 3.0 × 105 s−1. In regenerative solar cells with 0.5 M LiI and 0.005 M I2 in acetonitrile, incident photon-to-current efficiencies were typically less than 10%.  相似文献   

19.
Vascular smooth muscle cells (VSMCs) are exposed to mechanical cyclic stretch in vivo, which play important roles in maintenance of vascular homeostasis and regulation of pathological vascular remodeling. Reversible protein phosphorylation is crucial for intracellular signaling transduction. However, the dynamic phosphorylated profile induced by cyclic stretch in VSMCs is still unclear. Using the stable isotope labeling by amino acid in cell culture, VSMCs were labeled and exposed to 10% physiological cyclic stretch in vitro at 1.25 Hz for 0 min, 15 min, 30 min, 1 h and 6 h, respectively. Using TiO2 beads and liquid chromatography tandem mass spectrometry, the temporal phosphoproteomic profiles in response to cyclic stretch were then detected. Bioinformatics analysis including fuzzy c-means clustering, functional classifications, and Ingenuity Pathway Analysis were applied to further reveal the potential mechanotranduction networks. The results indicated that protein kinase C (PKCs) family, Rho-associated coiled-coil containing protein kinase 1 (ROCK1) and Akt may participate in cyclic-stretch induced VSMC functions. Cyclic stretch repressed the expression of ROCK1, while it had no significant effect on the phosphorylation of PKCα/βII, PKCζ/λ and PKCδ/θ. PKCθ was activated first at short time-phase (15 min and 30 min), and again at long time-phase (6 h, 12 h and 24 h). The activation of p-PKCμ was immediate and short-term, similar to p-Akt. Our present in vitro work hence revealed that cyclic stretch activates complex mechanotransduction networks, suggesting that novel mechanoresponsive molecules, i.e., PKCθ, PKCμ, and ROCK1, may participate in the mechanotransduction and modulation VSMC functions.  相似文献   

20.
Crystal structure of [ReO2(4-MeOpy)4][PF6] (4-MeOpy = 4-methoxypyridine) complex has been examined by the single crystal X-ray analytical method. This complex shows a trans-dioxo geometry (average Re-O bond length = 1.766(2) Å) and its equatorial plane is occupied by four 4-MeOpy molecules (average Re-N bond length = 2.156(4) Å). Electrochemical reaction of [ReO2(4-MeOpy)4]+ in CH3CN solution containing tetra-n-butylammonium perchlorate as a supporting electrolyte has been studied using cyclic voltammetry at 24 °C. Cyclic voltammograms show one redox couple around 0.65 V (Epa) and 0.58 V (Epc) [versus ferrocene/ferrocenium ion redox couple, (Fc/Fc+)]. Potential differences between two peaks (ΔEp) at scan rates in the range from 0.01 to 0.10 V s−1 are 65 mV, which is almost consistent with the theoretical ΔEp value (59 mV) for the reversible one electron transfer reaction at 24 °C. The ratio of anodic peak currents to cathodic ones is 1.04 ± 0.03 and the (Epa + Epc)/2 value is constant, 0.613 ± 0.001 V versus Fc/Fc+, regardless of the scan rate. Spectroelectrochemical experiments have also been carried out by applying potentials from 0.40 to 0.77 V versus Fc/Fc+ with an optically transparent thin layer electrode. It was found that the UV-visible absorption spectra show clear isosbestic points at 228, 276, and 384 nm, and that the electron stoichiometry is evaluated as 1.03 from the Nernstian plot. These results indicate that the [ReO2(4-MeOpy)4]+ complex is oxidized reversibly to the [ReO2(4-MeOpy)4]2+ complex. Furthermore, it was clarified that the [ReO2(4-MeOpy)4]2+ in CH3CN has the characteristic absorption bands at 236, 278, 330, 478, and 543 nm and their molar absorption coefficients are 4.3 × 104, 4.5 × 103, 1.0 × 104, and 6.1 × 103 M−1 cm−1 (M = mol dm−3), respectively.  相似文献   

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