共查询到20条相似文献,搜索用时 15 毫秒
1.
Matsuda R Anguizola J Joseph KS Hage DS 《Analytical and bioanalytical chemistry》2011,401(9):2811-2819
This study used high-performance affinity chromatography (HPAC) to examine the binding of gliclazide (i.e., a sulfonylurea
drug used to treat diabetes) with the protein human serum albumin (HSA) at various stages of modification due to glycation.
Frontal analysis conducted with small HPAC columns was first used to estimate the number of binding sites and association
equilibrium constants (K
a) for gliclazide with normal HSA and glycated HSA. Both normal and glycated HSA interacted with gliclazide according to a
two-site model, with a class of high-affinity sites (average K
a, 7.1–10 × 104 M−1) and a group of lower-affinity sites (average K
a, 5.7–8.9 × 103 M−1) at pH 7.4 and 37 °C. Competition experiments indicated that Sudlow sites I and II of HSA were both involved in these interactions,
with the K
a values for gliclazide at these sites being 1.9 × 104 and 6.0 × 104 M−1, respectively, for normal HSA. Two samples of glycated HSA had similar affinities to normal HSA for gliclazide at Sudlow
site I, but one sample had a 1.9-fold increase in affinity at this site. All three glycated HSA samples differed from normal
HSA in their affinity for gliclazide at Sudlow site II. This work illustrated how HPAC can be used to examine both the overall
binding of a drug with normal or modified proteins and the site-specific changes that can occur in these interactions as a
result of protein modification. 相似文献
2.
Christopher H. Evans Morgan Partyka Jan Van Stam 《Journal of inclusion phenomena and macrocyclic chemistry》2000,38(1-4):381-396
Naphthalene forms 1 : 1 complexes with -cyclodextrin (-CD)in water. The binding constant is 377 ± 35 M-1. Addition of linear or branched alcohols causes a reduction in the apparent strength of naphthalene binding (Kapp) compared to the value in the absence of additives. For example, 1% 1-pentanol reduces Kapp to 184 ± 31 M-1. Branching does not alter Kapp much for a given number of carbon atoms, e.g., it is 113 ± 9 M-1for 2-pentanol and 116 ± 8 M-1for 3-pentanol. The exception to this is tert-butanol for which Kapp is 577 ± 40 M-1. The variation in Kapp as a function of [1-pentanol] yields values for the individual equilibrium constants contributing to Kapp. This reveals that a ternary complex forms involving naphthalene, the CD and 1-pentanol. The constant for formation of the ternary complex is 99 ± 29 M-2. NaI quenching of naphthalene fluorescence indicates that the CD cavity partially protects the naphthalene excited state fromthis water phase quencher. Interestingly, the Stern–Volmer constant is lower in the presence of 1-pentanol than in its absence, although there should be more unbound (and therefore more NaI accessible) naphthalene in the former system than in the latter. These apparently contradictory results are discussed in terms of ternary complex formation. 相似文献
3.
Summary In acid perchlorate media, the title complex undergoes intramolecular redox decomposition generating ultimately Ag+ ion and oxidation products of the ligand. The reaction follows a simple first-order process, and the observed pseudo-first-order rate constant is given by kobs=k0+kKa/[H+] where Ka is the deprotonation constant of the parent complex; pKa is approximately 5.9 at 30°. The values of 105 k0(s–1) and 107 kKa (Ms–1) at 30°, I=1.0 M, are 9.3±0.1 and 11.8±1.3; corresponding H (kJ/mol), S (JK–1 M–1) values are 105±0.5, 23±1 and 79±8,-96±5, respectively. The results are compared with those for similar reaction of (ethylenebisbiguanide)silver(III) and effect of change in ligand structure on kinetic behaviours of these complexes is discussed. 相似文献
4.
James E. Pickett Jonathan R. Sargent Nicole Babbie 《Polymer Degradation and Stability》2009,94(7):1085-1091
The lifetime of polycarbonate (PC) coated with silicone hardcoats containing UV absorber is shorter at elevated temperatures. The activation energy (Ea) for delamination was found to be 18 ± 2 kJ/mol (4.3 ± 0.5 kcal/mol) at the 95% confidence level in this study. This Ea is the consequence of the sensitivity of the substrate and the UV absorber to temperature. The Ea for PC photodegradation was previously found to be 17-21 kJ/mol (4-5 kcal/mol). The Ea for loss of absorbance in the second-generation silicone hardcoat was found to be 28.5 ± 5.4 kJ/mol (6.8 ± 1.3 kcal/mol) at the 95% confidence level. Results are consistent with experimental findings when these activation energies are used in published predictive models. Since the Ea for coating delamination depends on the Ea of UV absorber loss, coating systems different from the one in this study will need to be investigated separately. 相似文献
5.
Apparent pK values of the wine pigment, 5-carboxypyranomalvidin-3-glucoside (vitisin A), were determined using UV-vis spectroscopy, viz. pKa1=0.98 (±0.10), pKH1=4.51 (±0.03) and pKH2=7.57 (±0.02). An additional ionisation constant at high pH (pKa4=8.84±0.06) was established by high-voltage paper electrophoresis. These data in conjunction with previously published pKa values determined by high-voltage electrophoresis suggest that in wine (pH 3.2-3.8), 5-carboxypyranomalvidin-3-glucoside exists as a complex mixture of hydrated and non-hydrated, partially ionised species with the predominant species being the quinonoidal base (λmax 498 nm). 相似文献
6.
Second‐order rate constants for the reactions of 2‐aryl‐4,6‐dinitrobenzotriazole 1‐oxides 1a‐d with some 4‐X‐substituted phenoxide ions 2a‐d (X = OCH3, H, Cl, and CN) have been measured in aqueous solution at 20°C. The pKa values for the σ‐complexation processes of a series of benzotriazole 1a‐d measured in water have been used to determine their electrophilicity parameters E according to the correlation E = –3.20 – 0.662 pKa (F. Terrier, S. Lakhdar, T. Boubaker, and R. Goumont, J Org Chem, 2005 , 70, 6242–6253). For these reactions, plots of log k versus the electrophilicity parameters E of the benzotriazoles 1a‐d were linear, allowing to derive the nucleophilicity parameters N and s for phenoxide ions as defined by the Mayr equation log k1 (20°C) = s (E + N) (H. Mayr, M. Patz. Angew Chem, Int Ed Engl 1994 , 33, 938–957). The N values are found to cover a range of nucleophilicity from 6.85 to 10.22, going from 4‐cyanophenoxide 2d for the least reactive ion to 4‐methoxyphenoxide 2a for the most reactive nucleophile. Good linear correlations were found between the nucleophilicity parameters N of phenoxide ions 2a‐d and the pKa values of their conjugate acids (N = –3.05 + 1.25 pKa) and the constants of the substituents X (N = 9.21 – 2.51). 相似文献
7.
The pyridinolysis of S-methyl chlorothioformate shows a biphasic Brønsted-type plot, in agreement with a stepwise mechanism and a change in the rate-limiting step, from formation of a zwitterionic tetrahedral intermediate (T±) at high pKa to its breakdown at low pKa. The reaction of the same substrate with secondary alicyclic amines shows a linear Brønsted-type plot of slope 0.23, which is in accordance with a stepwise mechanism where formation of T± is the rate-determining step for the whole pKa range examined. 相似文献
8.
Shu-ying Han Chao Liang Jun-qin Qiao Hong-zhen Lian Xin Ge Hong-yuan Chen 《Analytica chimica acta》2012
The retention factor corresponding to pure water in reversed-phase high performance liquid chromatography (RP-HPLC), kw, was commonly obtained by extrapolation of retention factor (k) in a mixture of organic modifier and water as mobile phase in tedious experiments. In this paper, a relationship between log kw and log k for directly determining kw has been proposed for the first time. With a satisfactory validation, the approach was confirmed to enable easy and accurate evaluation of kw for compounds in question with similar structure to model compounds. Eight PCB congeners with different degree of chlorination were selected as a training set for modeling the log kw ? log k correlation on both silica-based C8 and C18 stationary phases to evaluate log kw of sample compounds including seven PCB, six PBB and eight PBDE congeners. These eight model PCBs were subsequently combined with seven structure-similar benzene derivatives possessing reliable experimental Kow values as a whole training set for log Kow ? log kw regressions on the two stationary phases. Consequently, the evaluated log kw values of sample compounds were used to determine their log Kow by the derived log Kow ? log kw models. The log Kow values obtained by these evaluated log kw were well comparable with those obtained by experimental-extrapolated log kw, demonstrating that the proposed method for log kw evaluation in this present study could be an effective means in lipophilicity study of environmental contaminants with numerous congeners. As a result, log Kow data of many PCBs, PBBs and PBDEs could be offered. These contaminants are considered to widely exist in the environment, but there have been no reliable experimental Kow data available yet. 相似文献
9.
Q-mode curve resolution of UV-vis spectra for structural transformation studies of anthocyanins in acidic solutions 总被引:1,自引:0,他引:1
Chemometric analysis of ultraviolet-visible (UV-vis) spectra for pH values 1.0, 3.3, 5.3, and 6.9 was used to investigate the kinetics and the structural transformations of anthocyanins in extracts of calyces of hibiscus flowers of the Hibiscus acetosella Welw. ex Finicius for the first time. Six different species were detected: the quinoidal base (A), the flavylium cation (AH+), the pseudobase or carbinol pseudobase (B), cis-chalcone (CC), trans-chalcone (Ct), and ionized cis-chalcone (−CC). Four equilibrium constant values were calculated using relative concentrations, hydration, pKh = 2.60 ± 0.01, tautomeric, KT = 0.14 ± 0.01, acid-base, pKa = 4.24 ± 0.04, and ionization of the cis-chalcone, pKCC=8.74±1.5×10−2. The calculated protonation rate of the tautomers is KH+=0.08±7.6×10−3. These constants are in excellent agreement with those measured previously in salt form. From a kinetic viewpoint, the situation encountered is interesting since the reported investigation is limited to visible light absorption in acid medium. These models have not been reported in the literature. 相似文献
10.
Gemma Garrido 《Talanta》2007,73(1):115-120
Methanol is the organic solvent closest to water and able to dissolve a huge amount of organic compounds. Therefore, it is a good candidate for pKa determination of drugs sparingly soluble in water or a basic drug presented as a salt which pKa is close to that of its counter-acid. In this work, the acidic dissociation constants in pure methanol of the most common acids used in pharmaceutical preparations (lactic, tartaric, fumaric, maleic and citric) were determined. In addition, the pKa values of the antipsychotic quetiapine presented as hemifumarate (Seroquel) and the very insoluble antiarrhythmic amiodarone were also determined by potentiometry. From these values, the aqueous pKa of these drugs were estimated by means of previously established equations. Estimated values are consistent with those from literature and show the interest of methanol for drug discovery pKa measurements. 相似文献
11.
Saâdia Aziz Stéphane Dumas Mohammed El Azzouzi Mohamed Sarakha Jean-Marc Chovelon 《Journal of photochemistry and photobiology. A, Chemistry》2010,209(2-3):210-218
The photophysical and photochemical studies of a sulfonylurea herbicide, thifensulfuron-methyl (THM), have been investigated in a buffered aqueous solution. In the first part, the influence of pH on the spectroscopic properties was studied. This allowed the determination of the ground and excited state acidity constants, pKa = 4 and 4.4, respectively, thus exhibiting the potential existence of a photoinduced protonation in the singlet state. In the second part, the photolysis kinetics was studied at different pH and varying oxygen concentrations, using an HPK 125 W lamp and followed up by the identification of photoproducts formed under continuous photo-irradiation. The kinetics results suggest that the photolysis process is faster in acidic (k = 3 × 10?4 s?1) than in basic medium (k = 9.8 × 10?5 s?1). The photolysis products were identified by high performance liquid chromatography HPLC-DAD, HPLC–MS and HPLC–MS–MS. In order to obtain a better understanding of the photodegradation mechanism, a laser flash photolysis study was performed. By comparing the quenching rate constant (kq = 9.64 × 108 mol?1 l s?1) obtained from triplet state quenching by molecular oxygen and from the Stern–Volmer relation (kq = 0.41 × 108 mol?1 l s?1), the role of the singlet state in the photodegradation process was demonstrated. The photoproducts originating from both singlet and triplet excited states have been identified and hypothetical photodegradation pathways of the thifensulfuron-methyl in aqueous solution are proposed. 相似文献
12.
Among the metal-based anticancer drugs, cisplatin (cis-diaminedichloroplatinum(II)) is the most widely used species in therapy. Despite its clinical success, cisplatin still suffers in generating resistance, as well as being highly toxic due to poor selectivity between healthy and sick cells. By molecular design it ought to be possible to generate new cis-platinum compounds with increased selectivity and improved cellular behaviour. In this paper, we report a synthetic pathway for construction of derivatives of 1,1′-bis(diphenylphosphino)-ferrocene, together with their corresponding cis-platinum compounds with the aim testing them for their interaction capacity with respect to various DNA models. We also report a synthetic route for a nucleoside-based cis-platinum compound containing a bidentate ferrocenylphosphine derivative connected through a succinamic-based linker to the 5-position of the heterocyclic moiety of uridine. Our preliminary kinetic investigation of 5-{N-[1-[1′,2-bis(diphenylphosphino)ferrocenyl]ethyl]-N′-[prop-2-yn-3-yl]succinamide} uridinedichloroplatinum(II) showed that this compound reacted faster with the phosphorothioate containing oligonucleotides d(T6p(S)T6), with an observed first-order rate constant kobs=(1.4±0.1)×10−4 s−1, compared with the G-N7 target in d(T7GGT7), for which the observed first-order rate constant is kobs=(7.2±0.5)×10−4 s−1. 相似文献
13.
《Comptes Rendus Chimie》2002,5(6-7):525-528
Preparation and crystal structure determination (by X-ray single crystal measurements) of the K2PdCl2.81Br1.19, K2PdCl2.64Br1.36, K2PdCl2.41Br1.59, K2PdCl1.73Br2.27, and K2PdCl0.99Br3.01 compounds are reported. All these compounds crystallise in the same centrosymmetric space group P4/mmm. The tetragonal cell (a ≈ 7.3 Å; c ≈ 4.2 Å) contains one Pd atom, which lies on the C4 axis. The square-planar 〚PdX4〛2– ions (X = Cl, Br) are disordered. The Pd–X distances (2.348(2), 2.356(2), 2.362(2), 2.383(1), and 2.422(2) Å) have intermediate values between those previously observed for Pd–Cl (2.313 Å) in the K2PdCl4 compound and Pd–Br (2.444 Å) in the K2PdBr4 compound. 相似文献
14.
In this article, we present a systematic study on IgG and Fab fragment of anti-IgG molecules using fluorescence auto- and cross-correlation spectroscopy to investigate their diffusion characteristics, binding kinetics, and the effect of small organic molecule, urea on their binding. Through our analysis, we found that the diffusion coefficient for IgG and Fab fragment of anti-IgG molecules were 37 ± 2 μm2 s−1 and 56 ± 2 μm2 s−1, respectively. From the binding kinetics study, the respective forward (ka) and backward (kd) reaction rates were (5.25 ± 0.25) × 106 M−1 s−1 and 0.08 ± 0.005 s−1, respectively and the corresponding dissociation binding constant (KD) was 15 ± 2 nM. We also found that urea inhibits the binding of these molecules at 4 M concentration due to denaturation. 相似文献
15.
The determination of pKa value for the unstable chromium(VI) peroxide, CrO(O2)2(H2O) in aqueous solution is presented. The pKa value is found to be (1.55 ± 0.03). The kinetic decomposition of chromium(VI) peroxide is dependent on the concentration of hydrogen peroxide in the pH range between 2.5 and 4.0. We have proposed the possible explanation for the formation of triperoxo chromium complex of hydrogen peroxide which is dependent on decomposition. Activation of coordinate peroxide in chromium(VI) peroxide observed in the kinetic studies is by reduction of thiolato-cobalt(III) complex. The rate constant (M−1 s−1, 15 °C) for the oxygen atom transfer reaction from CrO(O2)2(OH)− to (en)2Co(SCH2CH2NH2)2+ is found to be (25.0 ± 1.3). 相似文献
16.
Giulia Cattaneo Daniela Ubiali Enrica Calleri Marco Rabuffetti Georg C. Höfner Klaus T. Wanner Marcela C. De Moraes Leonardo K.B. Martinelli Diógenes Santiago Santos Giovanna Speranza Gabriella Massolini 《Analytica chimica acta》2016
Mycobacterium tuberculosis (Mtb) purine nucleoside phosphorylase (PNP, EC 2.4.2.1) has been identified as a target for the development of specific inhibitors with potential antimycobacterial activity. We hereby described the development and validation of a new 96-well LC-ESI-MS/MS method to assess the inhibition activity of nucleoside analogues towards MtbPNP and the human PNP (HsPNP). Enzyme activity was determined by monitoring the phosphorolysis of inosine (Ino) to hypoxanthine (Hpx). The enzymatic assay (v = 0.5 mL, enzyme<0.2 μg/well, T = 37 °C) was performed with an overall time of about 15 min/plate for sample processing and 2 min/sample for LC-MS analysis. Validation of the quantification method met the criteria of the CDER guidance of FDA. Kinetic parameters were in agreement with those reported in literature (HsPNP KM = 0.150 ± 0.020 mM vs 0.133 ± 0.015 mM; MtbPNP KM = 0.060 ± 0.009 mM vs 0.040 ± 0.003 mM for Ino), thus demonstrating the reliability of the newly developed enzymatic assay. Preliminary inhibition assays confirmed the effects reported for Acyclovir (Acv) and Formycin A (FA) against HsPNP and MtbPNP. The validated enzymatic assay was applied to the evaluation of a set of 8-halo-, 8-amino-, 8-O-alkyl-substituted purine ribonucleosides synthesized on purpose as potential inhibitors against MtbPNP. The assayed 8-substituted ribonucleosides did not exert a significant inhibitory effect against the tested enzymes up to 1 mM. 相似文献
17.
XinAn Chen YaoZhong Zhang JianAn He ChunYang Xiong YongHong Meng Gang Jin HongWei Ma 《中国科学B辑(英文版)》2009,52(12):2307-2322
Surface initiated polymerization (SIP) is a valuable tool in synthesizing functional polymer brushes, yet the kinetic understanding
of SIP lags behind the development of its application. We apply quartz crystal microbalance (QCM) to address two issues that
are not fully addressed yet play a central role in the rational design of functional polymer brushes, namely quantitative
determination of the kinetics and the initiator efficiency (IE) of SIP. SIP are monitored online using QCM. Two quantitative
frequency-thickness (f-T) relations make the direct determination and comparison of the rate of polymerization possible even for different monomers.
Based on the bi-termination model, the kinetics of SIP is simply described by two variables, which are related to two polymerization
constants, namely a = 1/(k
p,s,app−[M][R·]0) and b = k
t,s,app/(k
p,s,app[M]). Factors that could alter the kinetics of SIP are studied, including (i) the molecular weight of monomers, (ii) the solvent
used, (iii) the initial density of the initiator, (iv) the concentration of monomer, [M], and (v) the catalyst system (ratio
among the ingredients, metal, ligands, and additives). The dynamic nature of IE is also described by these two variables,
IE = a/(a + bt). Instead of the molecular weight and the polydispersity, we suggest that film thickness, the two kinetic parameters (a and b), and the initial density of the initiator and IE be the parameters that characterize ultra-thin polymer brushes. Besides
the kinetics study of SIP, the reported method has many other applications, for example, in the fast screening of catalyst
system for SIP and other polymerization systems. 相似文献
18.
Christopher M. Timperley R. Eric Banks Ian M. Young Robert N. Haszeldine 《Journal of fluorine chemistry》2011,132(8):541-547
Fluoroheterocyclic aldoximes were screened as therapeutic agents for the treatment of anticholinesterase poisoning. 2-Fluoropyridine-3- and -6-aldoxime, and 3-fluoropyridine-2- and -4-aldoxime, were synthesised. Attempts to obtain 3,5,6-trifluoropyridine-2,4-bis(aldoxime) and -2-aldoxime, however, proved unsuccessful. Pentafluorobenzaldoxime was prepared by oximation of pentafluorobenzaldehyde. Acid dissociation constants (pKa) and second-order rate constants (kox−) of the fluorinated pyridinealdoximes towards sarin were measured. 2,3,5,6-Tetrafluoropyridine-4-aldoxime had the best profile: its kox− approached that of the therapeutic oxime P2S (310 vs. 120 l mol−1 min−1), but its higher pKa (9.1 vs. 7.8) fell short of the target figure of 8 required for reactivation of inhibited acetylcholinesterase in vivo. N-alkylation of the fluorinated pyridine-aldoximes may reduce their pKa nearer to 8 and enhance their therapeutic potential. 相似文献
19.
Columns containing immobilized low-density lipoprotein (LDL) were prepared for the analysis of drug interactions with this
agent by high-performance affinity chromatography (HPAC). R/S-Propranolol was used as a model drug for this study. The LDL columns gave reproducible binding to propranolol over 60 h of
continuous use in the presence of pH 7.4 0.067 M potassium phosphate buffer. Experiments conducted with this type of column
through frontal analysis indicated that two types of interactions were occurring between R-propranolol and LDL, while only a single type of interaction was observed between S-propranolol and LDL. The first type of interaction, which was seen for both enantiomers, involved non-saturable binding;
this interaction had an overall affinity (nK
a) of 1.9 (±0.1) × 105 M−1 for R-propranolol and 2.7 (±0.2) × 105 M−1 for S-propranolol at 37 °C. The second type of interaction was observed only for R-propranolol and involved saturable binding that had an association equilibrium constant (K
a) of 5.2 (±2.3) × 105 M−1 at 37 °C. Similar differences in binding behavior were found for the two enantiomers at 20 °C and 27 °C. This is the first
known example of stereoselective binding of drugs by LDL or other lipoproteins. This work also illustrates the ability of
HPAC to be used as a tool for characterizing mixed-mode interactions that involve LDL and related binding agents. 相似文献
20.
Single crystals of complex uranium oxides, CaUO4, β-Ca3UO6, K4CaU3O12 and K4SrU3O12 were grown from carbonate melts. The crystal structures of the four uranates were determined by single crystal X-ray diffraction. CaUO4 crystallizes in the hexagonal space group R-3m, with lattice parameters a = 6.2570(7) Å and α = 36.04(2)°. The U6+ atom in CaUO4 is 8-coordinate and exhibits hexagonal bipyramidal geometry with six long and two short U–O bonds, typical of a uranyl species. β-Ca3UO6 forms in the monoclinic space group P21/n, with lattice parameters a = 5.728(1) Å, b = 5.956(1) Å, c = 8.298(2) Å, and β = 90.55(3)°, and adopts a distorted double perovskite structure. K4CaU3O12 and K4SrU3O12 crystallize in the cubic space group Im-3m with lattice parameters a = 8.483(1) Å and a = 8.582(1) Å, respectively. In all three perovskite-type oxides, the U(VI) cation is located in an octahedral coordination environment and exhibits typical uranyl geometry with four long and two short U–O bonds. 相似文献