Herein, computational molecular docking, UV/visible and fluorescence spectroscopic techniques have been used to explore the DNA binding interactions of N-phthaloyl-β-alanine (NPA) ligand and its Zn(II) and Ni(II) complexes (NPAZn, NPANi). The compounds were further tested for anti-bacterial and anti-tumor activities. Docking analysis depicted that ligand NPA interacted with DNA via intercalation, while its metal complexes showed mixed mode of interactions. Spectroscopic experiments for DNA binding studies were run under physiological conditions of pH (stomach; 4.7, blood; 7.4) and temperature (37 °C). Based on changes in spectral responses, binding parameters for all the compounds were obtained which showed comparatively greater binding constant values (Kb: UV; 1.16 × 105 M−1, Flu; 1.35 × 105 M−1) and more negative free energy changes (ΔG: UV; −30.00 kJ mol−1, Flu; −30.44 kJ mol−1) for NPAZn at pH 4.7. The overall, binding results were also found more significant at stomach pH. Dynamic “KD” and bimolecular “KB” constants were evaluated, and the values affirmed the participation of static process for each compound–DNA binding. The greater binding site size values (n > 1) of metal complexes NPAZn and NPANi indicated other sites availability of intercalative compounds. DNA viscosity variation by increasing compound’s concentration further verified the compound–DNA interaction. Antibacterial and tumor inhibitory activities were observed significant for both metal complexes, while ligand has shown no activity. The greater binding affinity of metal complexes, as evaluated both computationally and spectroscopically, further validated the lower IC50 values of complexes as compared to ligand. 相似文献
The absorption spectrum of 16O3 has been recorded between 6030 and 6130 cm−1 by Fourier Transform Spectroscopy (GSMA, Reims) and cw-cavity ringdown spectroscopy (LSP, Grenoble). The two new bands 3ν1+3ν3 and 2ν2+5ν3 centered at 6063.923 and 6124.304 cm−1, respectively are observed and analyzed. Rovibrational transitions with J and Ka values up to 40 and 10, respectively, could be assigned. The rovibrational fitting of the observed energy levels shows that some rotational levels of the (303) and (025) bright states are perturbed by interaction with the (232), (510) and (124) dark states. The observed energy levels could be reproduced with a rms deviation of 5×10−3 cm−1 using a global analysis based on an effective Hamiltonian including the five interacting states. The energy values of the three dark vibrational states provided by the fit are found in good agreement with theoretical predictions.The parameters of the resulting effective Hamiltonian and of the transition moment operator retrieved from the measured absolute line intensities allowed calculating a complete line list of 2035 transitions, available as Supplementary Material. The integrated band strengths are estimated to be 1.22×10−24 and 3.15×10−24 cm−1/(mol cm−2) at 296 K for the 3ν1+3ν3 and 2ν2+5ν3 bands, respectively. A realistic error for these band strengths is 15% (see text). 相似文献
The differential capacitance/potential curves of two ionic liquid (IL) electrolytes, 1-butyl-3-methyl-imidazolium hexafluorophosphate (BMIM+/PF6−) and N-butyl-N-methyl-pyrrolidinium hexafluorophosphate (Pyr14+/PF6−) on a glassy carbon (GC) electrode were measured experimentally. The differential capacitance of BMIM+/PF6−/GC is higher in the negative polarization, while the differential capacitance of Pyr14+/PF6−/GC is higher in the positive polarization, although both ILs are composed of common anions, with cations of similar ionic structures and diameters. Such an opposite trend may be understood in terms of the specific adsorption between BMIM+ and the GC electrode, caused by the π-stacking interaction between the aromatic imidazolium ring and the sp2 graphite surface. The specific adsorption effectively shortens the electric double layer (EDL) thickness on the negatively charged electrode but elongates the EDL thickness on the positively charged electrode. Such an effect is manifested in the differential capacitance, with a higher value on the negative polarization branch than on the positive polarization branch. The impact of the specific adsorption is also seen from the positive shift of the potential of zero charge of BMIM+/PF6−/GC in comparison with that of Pyr14+/PF6−/GC. 相似文献
The gas-phase clustering reactions of proton in propanol and acetone, and chloride ions in acetone were investigated. The −ΔHn−1,n values obtained for clustering reactions (n−1,n) were as follows: H+ (C3H7OH)n−1 + C3H7OH ⇄ H+ (C3H7OH)n, (2, 3) 18.9 kcal mol−1, (3, 4) 14.2 kcal mol−1, (4, 5) 11.7 kcal mol−1; H+ (CH3COCH3)2 + CH3COCH3 ⇄ H+ (CH3COCH3)3, 14.2 kcal mol−1; and Cl− + CH3COCH3 ⇄ Cl− (CH3COCH3), 12.4 kcal mol.−1. For clustering reactions, Cl− (CH3COCH3n−1 + CH3COCH3 ⇄ Cl− (CH3COCH3)n where n ≥ 2, the equilibria could not be established; probably due to the isomerization of ligand acetone molecules from the keto to enol form. 相似文献
The electrooxidation of HCOONa was carried out over a wide range of pH on Pt. HCOO− and its associated form of HCOOH do not show any difference in electrochemical behaviour. A voltammetric study demonstrates the formation of two kinds of poisoning species in the hydrogen (X1) and double-layer (X2) regions. Their dependences on the potential and pH were examined. Constant polarization measurements give the rate expression, i = k(αH+)−0.43 exp(0.4Fφn/RT), independent of the concentrations of HCOO− and HCOOH. The rate-determining step is concluded to be HCOO− (a) → COO− (a)+H+ + e− or HCOOH(a) → COOH(a)+H+ + e−. The negative reaction order with respect to H+ was explained through the retarding action of X2. The nature of X1 and X2 is discussed. 相似文献
The 1 3Σg+ → a3Σu+ transition in the 7Li2 molecule has been observed in the 8200–10 000 cm−1 region with a high resolution Fourier spectrometer. Rotational analysis of 1 ⩽ υ′ ⩽ 7 of 1 3Σg+ and 0 ⩽ υ″ ⩽ 7 of a 3Σu+ has been carried out. We found De(a3Σu+) = 332.5 ± 1.0 cm−1 that gives Te(a3Σu+) = 8184.3 ± 1.5 cm−1 and De(1 3Σg+) = 7090.4 ± 1.5 cm−1 with Te = 16330 ± 2 cm−1. 相似文献
In the title compounds, C6H7N2O+·ClO4−, (I), and C6H7N2O+·C2HO4−, (II), the carboxamide plane is twisted from the plane of the protonated pyridine ring. Lamellar or sheet‐like structural features are observed through N—H⋯O and O—H⋯O hydrogen‐bonded motifs of cations and anions in (I) and (II), respectively. These sheets are aggregated through C(4) and C(5) chain motifs in (I) and (II), respectively. R12(4) ring motifs in (I) and R12(5) motifs in (II) are formed via pyridine–anion bifurcated N—H⋯O interactions. In (II), carboxamide groups form N—H⋯O dimers around the inversion centres of the unit cell, with R22(8) ring motifs. A 21 screw‐related helical or ribbon‐like structure along the b axis is formed in (II) through carboxamide and pyridinium N—H⋯O hydrogen bonds with the oxalate anions. 相似文献
The kinetics of the Fe(II) reduction of trans-chloro, bromo and iodopyridinebis(dimethylglyoximato)Co(III) have been studied at 30.0±0.1°C and I = 1.0 mol. dm−3(NaClO4) in the [H+] range 0.0043–0.115 mol. dm−3. The reaction showed an inverse dependence on [H+]. The second order rate constant could be expressed in the form kII = k1 + k2(1 + KB[H+])−1. The kinetic data were found to be: Co(DH)2(py)Cl−k1 = 0.051 ±0.003 dm3 mol−1s−1, 0.051±0.003 dm3 mol−1 s−1,k2 = 0.76±0.04 dm3 mol−1 s−1KB = 325±8 dm3 mol−1;Co(DH)2(py)Br-k1 = 0.071±0.004 dm3mol−1 s−1,k2 = 1.21±0.04 dm3 mol−1 s−1KB = 460±15 dm3 mol−1; Co(DH)2(py)I-k1 = 0.075±0.006 dm3 mol−1 s−1,k2 = 1.91±0.09 dm3 mol−1 s−1KB = 625±30 dm3 mol−1. The inverse dependence on [H+] suggests an inner-sphere mechanism involving protonated and unprotonated species of the complex. The order of rates for the three complexes was found to be Co(DH)2(py)I > Co(DH)2(py)Br > Co(DH)2(py)Cl. 相似文献
The energy levels of a new state of iodine monofluoride lying 5 eV above the ground state have been measured using the two-photon sequential absorption technique. Eleven vibrational levels of the state were measured. A vibrational and rotational analysis gives the spectroscopic constants as Te = 41291.96 cm−1, ωe = 248.76 cm−1, ωeχe = 0.4951 cm−1 and Be = 0.12920 cm−1. The state has 0+ character, and dissociates to I+ + F− in the diabatic approximation. 相似文献
The characteristics of H+−K+ exchange in anaerobically grown wild-type Escherichia coli K12(λ) performing nitrate/nitrite respiration are studied and compared with H+−K+ exchange in cells performing glycolysis. Unlike glycolysing cells, in which H+−K+ exchange takes place in two steps with different characteristics and inhibitor effects, H+−K+ exchange in E. coli K12(λ) with nitrate/nitrite respiration requires only one step. K+ uptake with a Km of 4.5 mM is not sensitive to N,N′-dicyclohexylcarbodimide (DCCD), but is inhibited by arsenate or protonophore. Such a K+ uptake is observed in the trkG mutant and is absent in the mutant with the trkA deletion. K+ accumulation is greater than 270 mM and the K+ gradient between the cytoplasm and the medium is comparable with the measured Δφ. The ratio of H+ to K+ flux through the membranes in the absence or presence of DCCD varies with the change in K+ external activity. A DCCD-sensitive ATPase activity in the isolated membranes of the trkG mutant is not stimulated by K+; such activity was lost in the trkG mutant with the deletion of the unc-operon. Moreover, H2 production by respiring cells is not observed. In addition, K+ uptake is osomosensitive and occurs under an upshock (i.e. an increase in the osmolarity of the medium). This osmosensitivity is lost in spheroplasts deprived of periplasmic space. The K+-uptaking TrkA system in E. coli worked as an ATP-driven pump by association with F1F0 in the united mechanism in glycolysing bacteria, and is assumed to operate as an uniport using ΔμH in cells with nitrate/nitrite respiration. This system has no ATPase activity and cannot carry out intramolecular dithiol-disulfide interconversion leading to H2 production. The interaction of the TrkA system with the F1F0 within the membrane is determined by a respiratory chain. This system is osmosensitive in anaerobically grown cells; osmoregulation can occur in a periplasmic space. 相似文献
Anionic species of aspartic acid, Asp−, having a zwitterionic backbone and a deprotonated side chain, appears to be a good example for analyzing dipole-ion and ion pair interactions. Density functional theory calculations were herein performed to investigate the low energy conformers of Asp− embedded in a dielectric continuum modeling an aqueous environment, through a scan of the potential energy as a function of the side chain (χ1, χ2) torsion angles. The most energetically favorable conformers having g+g− and g−g+ side chain orientations are found to be stabilized by charge-enhanced intramolecular H-bonding involving the positively charged () and the two negatively charged (COO−) groups. These conformers were further used to analyze Asp− + nW clusters (W: water, n = 1 or 3), and Asp−/Asp− pair formation. COO− groups were found to be the most attractive sites for hosting a water molecule (binding energy: −6.0 ± 1.5 kcal/mol), compared to groups (binding energy: −4.7 ± 1.1 kcal/mol). Energy separation between g+g− and g−g+ conformers increases upon explicit hydration. Asp−/Asp− ion pairs, stabilized by the interaction between the group of a partner and the COO− group of the other, shows a quite constant binding energy (−8.1 ± 0.2 kcal/mol), whatever the pair type, and the relative orientation of the two interacting partners. This study suggests a first step to achieve a more realistic image of intermolecular interactions in aqueous environment, especially upon increasing concentration. It can also be considered as a preliminary attempt to assess the interactions of the Lys+…Asp−/Glu− ion pairs stabilizing intra- and interchain interactions in proteins. 相似文献
The reactions of tetraphenylphosphonium ion (Ar4P+) with eaq−, H atoms and OH radicals have been investigated. The absorption spectra of three transient species were obtained. Ar4P· radicals formed by the reaction: Ar4P+ + eaq− → Ar4P· have a maximum absorption at 305 nm [ε305 = (9400 ± 300) dm3 mol−1 cm−1] and decays by second-order kinetics with the rate constant 2k = (2·7 ±0·4) × 109 dm3 mol−1 s−1. H atoms and OH radicals form transient adducts to the phenyl groups of the Ar4P+ ion with the rate constants of (1·5 ± 0·3) × 109 dm3 mol−1 s−1 and (3·0±0·3) × 109 dm3 mol−1 s−1, respectively. Both adducts have broad absorption spectra at 300≈380 nm (λmax = 340 nm) with the molar extinction coefficients ε340 = 5400±300 dm3 mol−1 cm−1 for the H adduct and ε340 = 3500±200 dm3 mol−1 cm−1 for the OH adduct. 相似文献
Reactions of organomagnesium halides with group 13 metal halides lead to the formation of R3M type compounds (R = alkyl, aryl; M = Al, Ga, In) and are considered as the simplest methods of R3M compound syntheses. These seemingly simple reactions reveal a much more complex chemistry involving mixed magnesium-group 13 metal compounds. To elucidate the reaction course of reactions of organomagnesium halides with group 13 metal halides, we have studied reactions of R3M with organomagnesium halides. The interaction of Et3M with R1MgX led to the formation of following products being mixtures of crystalline ionic complexes with the general composition of [Et4-nR1nM]−[XMg (thf)5]+·(thf): [Et2.2Al(CH=CH2)1.8]−[BrMg (thf)5]+·(thf) ( 1 ), [Et3Ga(CH=CH2)]−[BrMg (thf)5]+·(thf) ( 2 ), [Et4Al]−[BrMg (thf)5]+·(thf) ( 3 ), [Et4Ga]−[BrMg (thf)5]+·(thf) ( 4 ), [Et2.9Al(C6H5)1.1]−[BrMg (thf)5]+·(thf) ( 5 ), [Et2.9Ga(C6H5)1.1]−[BrMg (thf)5]+·(thf) ( 6 ), [Et3.4GaMe0.6]−[IMg (thf)5]+·(thf) ( 7 ) and [Et4In]−[BrMg (thf)5]+·(thf) ( 8 ). A comparison of the production course of group 13 metal trialkyls R3M with a thermal decomposition of 1–8 products showed that reactions of MX3 with RMgX (X = Br, I; R = alkyl, aryl) yield initially intermediate ionic compounds, which must then be thermally decomposed to obtain pure R3M compounds. If group 13 metal bromides and iodides, and alkyl (aryl)magnesium bromides and iodides in thf are used, only intermediate products with the [R4M]−[XMg (thf)5]+·(thf) structure are formed. 相似文献
The interaction of Fen(CO)m, (n and m equal 1 and 5, 2 and 9, 3 and 12, respectively) with 2-methyl-2-nitrosopropane and sodium salts of nitromethane and nitrocyclohexane was studied. The initial stages of the process, following the activating complex-formation, involves redox disproportionation to give rise to the radical Fe(I) carbonyl complexes and radical anions Fe2(CO)8−. (I) Fe3(CO)11−. (II), Fe4(CO)13−. (III) and Fe3(CO)12−. (IV). Also, radical anions I–IV are formed in the interaction of salts of carbonyl ferrate anions Na2Fe(CO)4·1.5 diox and PPN2[Fen(CO)m−1] (where PPN = (PPh3)2N+), with nitro- and nitroso-tert-butane.Radical anions I–III act as catalytically active species in the coordination sphere of which the nitro compounds undergo a successive deoxygenation to nitrene radical complexes with their subsequent carbonylation to isocyanates. A scheme of the reductive carbonylation is proposed. 相似文献
Cdk4 Inhibitors: Cyclins and cyclin-dependent kinases (Cdks) play important roles in regulation of the cell cycle. In particular, D-type cyclins, which are activated by rearrangement or amplification in several tumours, associate Cdk4/6. Cyclin D-Cdk4/6 complexes phosphorylate the retinoblastoma protein (pRB) and regulate the cell cycle during G1/S transition. Loss of function or deletion of p16ink4a (endogenous Cdk4/6 specific inhibitor protein) frequently occurs in clinical cancer cells. As a next generation of Cdk inhibitors, selective inhibitors of only one target Cdk are expected to cause cell cycle arrest specifically. Suppression of tumour growth by G1 arrest is thought to reduce the stress for normal cells more than in other phases, because normal cells are usually resting in the G0-G1 phase. Thus, the design of Cdk4 selective inhibitors that cause cell cycle arrest in the G1 phase has been attempted [2] (Structure-based generation of a new class of potent Cdk4 inhibitors: New de novo design strategy and library design, Honma, T. et. al., J. Med. Chem., 44, (2001), 4615-4627). To obtain highly selective and potent Cdk4 inhibitors a structure-based design was performed which consisted of lead generation of a new class of Cdk4 inhibitors based on a Cdk4 homology model, and enhancement of Cdk4 selectivity of lead compounds over Cdk1/2 and other kinases based on the binding modes and structural differences between Cdk4 and other kinases. This methodology was applied to search the Available Chemicals Directory and 382 commercial compounds were selected for screening in cyclin D-Cdk4 assays at concentrations up to 1mM. From this set, 18 compounds were found which possessed an IC50 value of under 500 mM. From these hits, a class of diarylureas were identified with the potential for parallel synthesis follow up to validate the potential of the scaffold and to obtain preliminary SAR. 410 Urea compounds were then designed and synthesised as singles in solution, the design based on the diarylurea hits, and they were screened in a Cdk4 inhibition assay. One of the most potent compounds isolated was (i) which possessed an IC50 value of 34 nM. This work has utilised a structure-based lead generation approach consisting of homology modelling of the target protein, construction of a library of compounds, followed by modification of hits obtained based on predicted binding mode. This strategy has provided potent compounds from a new class of diarylurea Cdk4 inhibitors and may lay the foundation for further work to improve potency in this series. 相似文献
The electronic absorption spectra of compounds containing metal-metal triple bonds of σ2π4 valence electronic configuration are presented and discussed. The lowest-energy transition of M2L6 compounds (M = Mo or W, L = CH2But or OBut) is expected to be the dipole-allowed π → π* (eu → eg) transition. This appears to be the case for M2(CH2But)6 and M2(OBut)6 compounds, in which the lowest energy absorption bands occur between 26,000 and 28,000 cm−1 (ε = 1.1 x 103-1.8 x 103 M−1 cm−1). For M2(NMe2)6 compounds, the lowest energy absorption is not the π → π* transition but is assigned instead to a LMCT transition originating from nitrogen lone-pair orbitals, N1p → π*, observed at 30,800 cm−1 (ε = 1.4 x 104-1.9 x 104 M−1 cm−1). The π → π* transition is not observed in these compounds, but is presumably masked by the more intense LMCT. These assignments are derived from Xα-SW calculations performed and described by other authors (Bursten et al., J. Am. Chem. Soc. 1980, 102, 4579). 相似文献
The reduction mechanism of 1-alkyl-2-cyanopyridinium (2(CN)+) and 1-alkyl-3-cyanopyridinium (3(CN)+) has been investigated in acetonitrile using dc, normal pulse (NP) and reverse pulse polarography (RP).The reduction of 2(CN)+ at low concentraions (< 4 × 10−5M) and short pulse widths (tp < 2 ms) leads to the formation of the radical 2(CN) in a reversible process with E°′ = −1028±2 mV. At longer times, dimerization of the radicals occurs at the 2-, 4- and 6-positions, leading predominantly to 4,4′- and 4,2′-dimers (all dimers denoted by D(CN)2). Fast interconversion of linking positions takes place. 4,4′-Dimers are the predominant species. 2,4′-Dimers, although minor species, enable a path for one cyano group to be lost in a homogeneous reaction, resulting in a new pyridinium ion, D(CN)+. This pyridinium ions is reduced further at potentials more negative than 2(CN)+. Cyanide ions react with 2(CN)+ to form 2,4-dicyano-1-methyl-1,4-dihydropyridine. The rate of this reaction is relatively slow in the presence of LiClO4 (kf = (8±0.5) s−1M−1, kb = (2.3±0.2)×10−3 s−1, log (K/M−1)=(3.5+0.1)) and is much faster in TBAP. During the electrochemical reduction of 2(CN)+, during which cyanide ions are released, reaction (5) takes place, causing a decrease in the polarographic limiting current in TBAP, but not in LiClO4.The reduction of 3(CN)+ consists of a single charge transfer followed by irreversible dimerization. 相似文献
The fluorescence spectrum of all-trans-β-carotene was recorded at 170 K. The 1Bu+ → 1Ag− fluorescence exhibited clear vibrational structures constituting a mirror image with those of the 1Bu+ ← 1Ag− absorption, and the deconvolution of the entire spectrum identified the 2Ag−(0) → 1Ag−(0) transition at 14 500 cm−1. The displacements of the 1Bu+ and 2Ag− potential minima along ν1 and ν2 (the CC stretching and C–C stretching normal coordinates, respectively) were determined to be 1.2 and 0.9, and 1.6 and 1.5, respectively. Thus, much larger potential displacements in the 2Ag− state than in the 1Bu+ state have been shown. 相似文献
The vibrational spectra of the following compounds were measured: X+AlMe−4; X+GaMe−4 and X+InMe−4 (with X = Na, K, Me4P+, Me4As+ or Me4Sb+). For the purpose of comparison the spectra of compounds of group IV and V elements were taken from the literature or measured a second time. With a new procedure for determination of force-constants a set of comparable force-constants for the tetramethyl compounds of the elements Al, Si, P/Ga, Ge, As/In, Sn, Sb was obtained. 相似文献
A new method for the speciation of inorganic lead and trialkyllead compounds involving the selective separation of the analytes in a continuous system and their subsequent introduction into a flame atomic absorption spectrometer was developed. The proposed flow system consists of two units. In the first unit, total inorganic lead at concentrations from 8 to 200 ng ml−1 is continuously precipitated as lead chromate and the filtrate, containing trialkyllead cations, is collected in a vessel, the precipitate then being dissolved in diluted acid and driven to the instrument. In the second unit, trimethyllead (TML+) and triethyllead (TEL+) cations at ng ml−1 levels are complexed with sodium diethyldithiocarbamate and retained on a C60 pre-conditioned fullerene column; the mixture of both species was resolved by conditioning the sorbent column with n-hexane or isobutyl methyl ketone solvents. Detection limits of 1–2 ng ml−1 can be achieved by using a sample volume of 50 ml. Special attention was given to the reliability and robustness of the global flow injection method in assessing its applicability to both types of organolead compounds and inorganic lead present in different proportions. Trimethyllead provides the poorest results as consequence of its low adsorption constant on C60; however, the three different types of species (Pb2+/TML+/TEL+) can be effectively determined in proportions from 1:1:1 to 30:12:1 with relative errors less than 10%. 相似文献