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1.
The effect of 2-hydroxypropyl-β-cyclodextrin (HPβCD) on solubility, stability and oral bioavailability of curcumin by external factors adjustment, was investigated with an aim of a simple, stable and effective formulation. The phase solubility studies showed the solubility of curcumin increased slightly with increasing pH. However, the apparent stability constant (K S) were found to decrease with increasing pH from 1.29?×?104?M?1 at pH 3.0 to 5.22?×?103?M?1 at pH 7.0. The thermodynamic parameters were calculated for inclusion complex formation in aqueous solution. Interestingly, it could be concluded that the degrees of curcumin stability improved by HPβCD grew with increasing drug–cyclodextrin binding ability. Furthermore, in vivo study not only revealed that the bioavailability of curcumin after oral administration to rats was significantly improved by curcumin/HPβCD inclusion complex, but also showed more dramatic changes in the plasma concentration–time curve (1752.76–866.70?ng?mL?1?h) and the peak plasma concentration (370.10–178.11?ng?mL?1) of drug by formation of complexes in pH 3–7 solution.  相似文献   

2.
The interaction between β-cyclodextrin (β-CD) and the polyphenol rosmarinic acid (RA) is here reported by 1H NMR titration experiments. The formation of an aqueous soluble inclusion complex is confirmed and valuable information regarding mode of penetration of guest into β-CD, stoichiometry, and stability of the complex is obtained. The analysis by the continuous variation method shows the undoubted formation of 1:1 β-CD/RA complex. Additionally, the estimated apparent association constants reveal the importance of the asymmetry of the RA in the complexation; the incorporation of the catechol moiety closer to the carboxylic group is more favorable (K?=?2,028 M?1) than from the other end of the RA molecule (K?=?1,184 M?1). Finally, we have also investigated the antioxidant activity and storage stability of the β-CD/RA complexed system; the presence of β-CD was found to produce a remarkable enhancement on the antioxidant activity.  相似文献   

3.
Three selective CB2 cannabinoid receptor ligands have recently been discovered to be promising anti-inflammatory agents but their low water solubility hinder their per os administration. The popularity of the cyclodextrins, from a pharmaceutical standpoint lies on their ability to interact with poorly water-soluble drugs and improve their solubility. Herein, three experimental approaches for calculating the stability constant of complexes between the selective CB2 ligands and either the β-CD or the HP-β-CD, were tested: nuclear magnetic resonance, micellar electrokinetic chromatography and high performance liquid chromatography in reversed phase. In NMR studies the calculated K values were relatively high and were between 1486 and 3571 M?1 with β-CD. With HP-β-CD they were between 1203 and 2650 M?1. Concerning the two others techniques the K values were found lower. In MECK studies with β-CD they were between 308 and 792 M?1 and with HP-β-CD between 124 and 764 M?1. Finally in RP-HPLC studies with β-CD, they were between 539 and 1144 M?1 and with HP-β-CD between 196 and 396 M?1. These calculated constants suggest that a complexation phenomenon occurs. A model for inclusion of one of the CB2 ligands in the β-CD was then proposed from molecular modeling studies.  相似文献   

4.
The enzyme Na+, K+-ATPase is an integral membrane protein which transports sodium and potassium cations against an electrochemical gradient. The transport of Na+ and K+ ions is connected to an oscillation of the enzyme between the two conformational states, the E1 (Na+) and the E2 (K+) conformations. The enzymatic activity of ATPase is largley affected by different ligands complexation. This review reports the effects of several drugs such as AZT (anti-AIDS), cis-Pt (antitumor), aspirin (anti-inflammatory) and vitamin C (antioxidant) on the stability and secondary structure of Na,K-ATPase in vitro. Drug-enzyme binding is mainly through H-bonding to the polypeptide C=O and C-N groups with two binding constants K1(AZT) = 5.30 × 105 M?1 and K2(AZT) = 9.80 × 103 M?1 for AZT and one binding constant for Kcis-Pt = 1.93 × 104 M?1, Kaspirin = 6.45 × 103 M?1 and Kascorbate = 1.04 × 104 M?1 for cis-Pt, aspirin and ascorbic acid. The enzyme secondary structure was altered from that of α-helix 19.8% (free protein) to almost 22–26% and the β-sheet from 25.6% to 18–22%, upon drug complexation with the order of induced stability AZT > cis-Pt > ascorbate > aspirin.  相似文献   

5.
Methylated cyclosophoraoses (M-Cys) were synthesized by reaction using dimethyl sulfate with native Cys (unbranched cyclic β-1,2-d-glucans) isolated from Rhizobium leguminosarum biovar viciae VF-39. Its structure was proven using nuclear magnetic resonance (1H NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Based on the enhanced hydrophobicity by methylation of Cys, we investigated the inclusion property with the water-insoluble flavonoid, galangin, through a phase solubility study using ultraviolet–visible spectroscopy. The solubility of galangin was enhanced 5.6-fold according to the added concentrations (1 mM) of M-Cys, compared to the 1.9-fold and 3.4-fold enhancements by β-Cyclodextrin (β-CD) and heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), respectively. M-Cys was also shown to have the highest binding constant (5,534 M?1) with galangin among the tested host molecules (β-CD, DM-β-CD, Cys, and M-Cys). From this result, we can infer that the complex of galangin with M-Cys is more stable than any of the other host molecules. The continuous variation method showed that the galangin/M-Cys complex was suitable for 1:1 stoichiometry. The formation of the complex was confirmed with 1H NMR, FT-IR, differential scanning calorimetry, and scanning electron microscopy. Furthermore, the hypothetical molecular model of 1:1 galangin/M-Cys complex was suggested by molecular docking simulations. The cytotoxicity to the human cervical adenocarcinoma cell lines was enhanced by the galangin/M-Cys complex compared with free galangin. The obtained results indicate that M-Cys can be utilized as an effective complexing agent for galangin.  相似文献   

6.
The protonation and complex formation equilibria of two biodegradable aminopolycarboxylate chelants {dl-2-(2-carboxymethyl)nitrilotriacetic acid (GLDA) and 3-hydroxy-2,2??-iminodisuccinic acid (HIDS)} with Ni2+, Cu2+, Zn2+, Cd2+ and Pb2+ ions were investigated using the potentiometric method at a constant ionic strength of I?=?0.10?mol·dm?3 (KCl) in aqueous solutions at 25?±?0.1?°C. The stability constants of the proton?Cchelant and metal?Cchelant species for each metal ion were determined, and the concentration distributions of various complex species in solution were evaluated for each ion. The stability constants (log10 K ML) of the complexes containing Ni2+, Cu2+, Zn2+, Cd2+ and Pb2+ ions followed the identical order of log10 K CuL?>?log10 K NiL?>?log10 K PbL?>?log10 K ZnL?>?log10 K CdL for either GLDA (13.03?>?12.74?>?11.60?>?11.52?>?10.31) or HIDS (12.63?>?11.30?>?10.21?>?9.76?>?7.58). In each case, the constants obtained for metal?CGLDA complexes were larger than the corresponding constants for metal?CHIDS complexes. The conditional stability constants (log10 $ K_{\text{ML}}^{'} $ ) of the metal?Cchelant complexes containing GLDA and HIDS were calculated in terms of pH, and compared with the stability constants for EDTA and other biodegradable chelants.  相似文献   

7.
Immobilization of cyclodextrin on the surface of silica was performed using citric acid as the bonding agent. Inclusion complexes of atrazine with free (CD) or anchored (CDSI) β-cyclodextrin were prepared and then characterized using infrared spectroscopy, X-ray diffraction and differential scanning calorimetry. The complexation reaction showed first order kinetics, with a rate constant (k) of 8.72?×?10?3 min?1. There was a rapid increase of absorbance in the first 40?min, followed by attainment of equilibrium after ~2?h. The stoichiometry of the reaction was 1:1, with both free and anchored β-cyclodextrin increasing the solubilization of atrazine in an aqueous medium (by around 1.5 and 3.4 times, respectively). The association constant (K a) of the complex was 28.93?L?mol?1 using CD and 130.68?L?mol?1 using CDSI. In release tests, 62% of the atrazine complexed with CDSI or β-CD was released after 40?h, while 83% of free atrazine was released during the same period.  相似文献   

8.
The title cluster is luminescent at 77?K and exhibits an unsaturated site for binding anions when the counter ion is PF6 ?. A series of five non-luminescent metalloporphyrins exhibiting carboxylate anchoring groups were synthesized and characterized. These are the sodium salts of the 5-carboxyphenyl-tri-10,15,20-tolyl-, trans-di-5,10-carboxyphenyl-di-15,20-tolyl-, and tetra-5,10,15,20-carboxyphenyl(metallo)porphyrin (metallo?=?chloroiron(III), nickel(II)) anions. Evidence for supramolecular assemblies between the carboxylates and the cluster is provided by 31P NMR and UV?Cvis spectroscopy. The binding constant, K1n, extracted from the UV?Cvis data via Benesi-Hildebrand, Scott and Scatchard plots are approximately 21,000?±?5,000?M?1 for the nickel(II) species, in agreement with the previously reported zinc(II) ones (K11?=?20,000?±?2,000?M?1), but those for the chloroiron(III) are measured to be lower (12,500?±?3,500?M?1). This association is accompanied by a complete quenching of the luminescence of the cluster which can only be due to an efficient energy transfer to the d?Cd states of the chloroiron(III) and nickel(II) species but an electron transfer from the nickel(II)-containing chromophore to the cluster is also possible. This work demonstrates the profound effect that supramolecular interactions may have on the photophysical properties despite the long donor?Cacceptor separation.  相似文献   

9.
The interaction between a water-soluble cationic fluorescent conjugated polymer (WCFP) and bovine serum albumin (BSA) was studied using UV?CVis absorption, fluorescence and circular dichroism spectroscopies. The results show that the fluorescence of BSA is strongly quenched by the WCFP under physiological conditions (pH?=?7.4). The quenching mechanism was found to be static, which was confirmed by the quenching rate constant (Kq) and UV?CVis absorption spectra. The thermodynamic parameters (?H ??, ?S ?? and ?G ??) calculated from the complexation constant, determined according to Lineweaver?CBurk equations are 38.6?kJ·mol?1, 228?J·mol?1·K?1 and ?29.4?kJ·mol?1 at 298?K. The principal interaction was proposed to be electrostatic.  相似文献   

10.
A new ionic compound (3-ATz)+ (NTO)?C was synthesized by the reaction of 3-amino-1,2,4-triazole (3-ATz) with 3-nitro-1,2,4-triazol-5-one (NTO) in ethanol. The single crystals suitable for X-ray diffraction measurement were obtained by crystallization at room temperature. The crystal is monoclinic, space group p 2(1)/c with crystal parameters of a?=?0.6519(2)?nm, b?=?1.9075(7)?nm, c?=?0.6766(2)?nm, ???=?94.236(4)°, R 1?=?0.0305 and wR 2?=?0.0789. The thermal behaviors were studied, and the apparent activation energy and pre-exponential constant of the exothermic decomposition stage were obtained by Kissinger??s method and Ozawa??s method. The self-accelerating decomposition temperature is 505.40?K, and the critical temperature of the thermal explosion is obtained as 524.90?K. The specific heat capacity was determined with Micro-DSC method and the theoretical calculation method, and the standard molar specific heat capacity is 221.31?J?mol?1?K?1 at 298.15?K. The Gibbs free energy of activation, enthalpy of activation, and entropy of activation are 151.55?kJ?mol?1, 214.52?kJ?mol?1 and 122.44?J?mol?1?K?1. The adiabatic time-to-explosion of the compound was estimated to be a certain value between 5.0 and 5.2?s, and the detonation velocity (D) and pressure (P) were also estimated using the nitrogen equivalent equation according to the experimental density.  相似文献   

11.
In exploring the capability of nuclear magnetic resonance (NMR) spectroscopy for pomegranate juice analysis, the eight aromatic singlet resonances of α- and β-punicalagin were clearly identified in the 1H NMR spectra of juice samples. The four downfield resonances were found to be sensitive to small pH changes around pH 3.50 where the NMR spectra of the juice samples were recorded. To understand this unusual behavior, the 1H and 13C resonance assignments of the punicalagin anomers were determined in aqueous solution and pH titrations with UV and 1H NMR detection carried out to characterize the acid–base properties of punicalagin over the pH range 2–8. Simultaneous fitting of all of the pH-sensitive 1H NMR signals produced similar but significantly different pK a values for the first two deprotonation equilibria of the gallagic acid moiety of the punicalagin α- (pK a1?=?4.57?±?0.02, pK a2?=?5.63?±?0.03) and β- (pK a1?=?4.36?±?0.01, pK a2?=?5.47?±?0.02) anomers. Equivalent pK a values, (α?:?6.64?±?0.01, β?:?6.63±?0.01) were measured for the third deprotonation step involving the ellagic acid group, in good agreement with a prior literature report. The punicalagin anomer equilibrium readjusts in parallel with the proton dissociation steps as the pH is raised such that β-punicalagin becomes the most abundant anomer at neutral pH. The unusual upfield shifts observed for the glucose H3 and H5 resonances with increasing pH along with the shift in the α/β anomer equilibrium are likely the consequence of a conformational rearrangement.
Figure
Titration of the punicalagin phenolate protons over the pH range 2–8 results in changes in the aromatic proton chemical shifts and a readjustment of the anomer equilibrium.  相似文献   

12.
Tiagabine (TGB) is an antiepileptic agent enhancing the activity of GABA at neuronal and glial region. It has recently been shown that enhancement of TGB chemical stability was improved by complexation with 2-hydroxypropyl-beta-cyclodextrin (2-HPβCD). The aim of this project is to explain the improvement of the chemical stability of complexed TGB by studying the inclusion properties and factors affecting the complexation selectivity between 2-HPβCD and TGB. Analysis of the interaction between 2-HPβCD and TGB and the effect of 2-HPβCD on TGB solubility was performed by phase solubility method described by Higuchi and Connors; the complexation was followed by characterization using DSC, FTIR and NMR spectroscopy. In aqueous media, the analysis of NMR proton shift change continuous variation method (Job’s plot) and the NMR diffusion-ordered spectroscopy (DOSY) measurements clearly show that TGB form 1:1 inclusion complex with 2-HPβCD with an association constant (K a) of 3396 M?1. More detailed information about the inclusion mode and the geometry of the complex was obtained by the analysis of 2D NMR NOESY experiment and molecular modelling calculations. The inclusion process indicates that A-ring, C10–C11 double bond and the half of the B-ring of TGB molecule were located inside the cavity while the nipecotic acid part of TGB (Ring C) was exposed towards the outside of the 2-HPβCD cavity. These results suggest that the inclusion of the C10–C11 double bond in the 2-HPβCD cavity may possibly the reason of improvement of TGB chemical stability.  相似文献   

13.
Host?guest complexation has been studied by 1H NMR on the benzyl and phenethyl amides of ferulic and caffeic acids as the guests in chloroform and acetonitrile; the counter host is a cyclophane which integrates four phenylene rings, amino and amide groups in the macrocyclic framework and bears four pendant methyl acetate ester arms. CAPE, one of the best known natural antioxidants, also has been studied for comparison. Among the guests studied, ferulic acid benzyl amide shows NMR shifts due to the formation of a host?guest complex in chloroform. The complexation occurs in two steps with the formation constants K 1?=?[HG]/[H][G]?=?6?M?1 and β 2?=?[HG2]/[H][G]2?=?87?M?2. Two guest molecules are bound on the surface of the macrocyclic framework of a host molecule by two hydrogen bonds, NH(host amide)···O=C(guest amide) and C=O(host ester)···HO(guest phenol). The latter hydrogen bond may protect the bioactive site, i.e., phenol OH, of guest molecules captured in the complex against undesirable oxidation. This feature is observed only for ferulic acid benzyl amide in chloroform; the cyclophane ester interacts with this amide, distinctively from the other hydroxycinnamic acid derivatives.  相似文献   

14.
The complexation reactions of iron(III) with 2-pyridine carboxylic acia (picolinic acid) and 2,6-pyridine dicarboxylic acid (dipicolinic acid) in aqueous solutions have been studied by spectrophotometric and stopped flow techniques. Equilibrium constants were determined for the 1 : 1 complexes at temperatures between 25 and 80°C. The values obtained are: Picolinic Acid (HL): Fe3++ H2L+? FeHL3++H+(K1 = 2.8,ΔH = 2 kcal mole?1 at 25°C, μ = 2.67 M) Dipicolinic Acid (H2D): Fe3++H2D? FeD++2H+(K1K1A= 227 M, ΔH = 3.4 kcal mole?1 at 25°C,μ = 1.0 M). The rate constants for the formation of these complexes are also given. The results are used to evaluate the effects of these two acids upon the rate of dissolution of iron(III) from its oxides.  相似文献   

15.
J.G. Leipoldt  H. Meyer 《Polyhedron》1985,4(9):1527-1531
The reaction of Cl?, Br?, I?, Co(CN)63? and NCS? with meso-tetrakis (p-trimethylammoniumphenyl)porphinatodiaquorhodate(III), [RhTAPP(H2O)2]5+, has been studied at 15, 25 and 35°C in 0.1 M [H+] with μ = 1.00 M (NaNO3). The value of the acidity constant, Kal, at 25°C is 4.39 × 10?9 M. The reactions are first order in anion concentration up to 0.9 M. The values of the stability constants, K1, and the second order rate constants, k1, for the reaction with Cl?, Br?, I?, Co(CN)63? and NCS? are respectively 0.23 M?1 and 2.5 × 10?3 M?1 s?1, 1.1 M?1 and 6.92 × 10?3 M?1 s?1, 40.0 M?1 and 17.0 × 10?3 M?1 s?1, 550 M?1 and 20.0 × 10?3 M?1 s?1, 3400 M?1 and 20.9 × 10?3 M?1 s?1. The porphine greatly labilizes the Rh(III). There has been about a 500-fold increase in the rate constant for substitution compared to that of [Rh(NH3)5H2O]3+. The substitution rates are however about the same as for [Rh(TPPS)(H2O)2]3?, indicating that the overall charge on the complex plays only a minor role. The kinetic results indicate that dissociative activation is occurring in these reactions.  相似文献   

16.
The study of D(?)-ribose complexing with calcium in aqueous solutions less than 1.64 × 10?1M by potentiometric measurements with a calcium selective electrode afforded the value of K1 = 1.70 liters × mole?1 (SD = 1.05 × 10?3). Numerical analysis indicated that complex species with 1:1 and 1:2 calcium to D(-)-ribose ratios are present simultaneously: k1 = 1.13 liters × mole?1 and K2 = 8.47 liters × mole?1 (SD = 0.95 × 10?3).In methanolic medium 1.24 × 10?2M with regard to calcium chloride both stoichiometric proportions were evidenced. A large error accompanying the stability constant K1 = 28 kg × mole?1 (RSD = 82%) renders unreasonable the K2 value obtained from the product K1 × K2 = 96.5 kg2 × mole?2.The results are discussed with respect to the data published for more concentrated (1.27 M) aqueous solutions obtained on the basis of 1H-NMR spectroscopic investigations.  相似文献   

17.
From extraction experiments and γ-activity measurements, the exchange extraction constants corresponding to the general equilibrium M+(aq)?+?1·Cs+(nb) ? 1·M+(nb)?+?Cs+(aq) taking place in the two-phase water–nitrobenzene system (M+?=?Li+, Na+, K+, Rb+, H3O+, NH4 +, Tl+; 1?=?beauvericin; aq?=?aqueous phase, nb?=?nitrobenzene phase) were determined. Moreover, the stability constants of the 1·M+ complexes in water-saturated nitrobenzene were calculated; they were found to increase in the series of Rb+?<?Na+, H3O+?<?Tl+?<?NH 4 +? <?K+?<?Li+.  相似文献   

18.
Biodegradation of styrene by Exophiala sp. was tested at different initial concentrations (19.3?C170.6?mg?l?1), pH (2.8?C8.7), and temperatures (19.8?C45.1?°C), for 120?h according to a 23 full-factorial central composite design. The specific growth rate (SGR, per hour) and specific styrene utilization rate (SUR, milligrams of styrene per milligram of biomass per hour) values were used as the response variables for optimization purposes. The interactions between concentration and temperature (P?=?0.022), and pH and temperature (P?=?0.010) for SGR, and interactions between concentration and temperature (P?=?0.012) for SUR were found to be statistically significant. The optimal values for achieving high SGR (0.15?h?1) and SUR (0.3622?mg styrene mg?1 biomass h?1) were calculated from the regression model equation. Those values are C o ?=?89.1?mg?l?1, pH?=?5.4, and T?=?31.5?°C for SGR and C o ?=?69.2?mg?l?1, pH?=?5.5, and T?=?32.4?°C for SUR. It was also observed that the Exophiala strain degrades styrene via phenylacetic acid, involving initial oxidation of the vinyl side chain. Besides, in the presence of styrene, changes in the fatty acids profile were also observed. It is hypothesized that an increasing amount of linoleic acid (18:2) may be involved in the protection of the fungus against toxic substrate.  相似文献   

19.
1-Amino-3-methoxypropane (3MPA) and 2-dimethylaminoethanol (DMAE) are potential volatile amines for boiler water treatment and were investigated for their complexation behaviour with copper. Their pKb values were 3.67 and 4.52 at 25°C and they formed coloured complexes with absorption in the region of 644 and 510 nm, respectively. In the pH range 10–11, the Cu-3MPA complex exhibited stepwise reduction and [Cu(3MPA)2]+ was identified, with a stability constant of 109.52. In the pH range 8–10.5, the Cu-DMAE complex exhibited 2e? reduction and the species [Cu(DMAE)2(OH)2] was identified, with a stability constant of 1020.39. A correlation between visible and ESR spectra and reduction behaviour was established.  相似文献   

20.
P.G. David 《Polyhedron》1985,4(3):437-440
Complex formation between copper(II) and bromide in anhydrous methanol was investigated spectrophotometrically. At a constant copper(II) concentration of 3.0 x 10?4M, Cu2+ and CuBr+ are at equilibrium for [Br?] < 1.0 x 10?3M while CuBr+ and CuBr2 exist at equilibrium in the range of [Br?] 2.0 x 10?3 ?40 x 10?3M. An isosbestic point at 235 nm indicated the equilibrium of Cu2+ and CuBr+ while a second isosbestic point at 290 nm showed the equilibrium of CuBr+ and CuBr2. Stability constants for the formation of CuBr+ and CuBr2 (K1, and K2, respectively) were determined as a function of ionic strength in the range 0.01–0.10. Log K1 and log K2 values at zero ionic strength were obtained by extrapolation of the plot of log K vs ionic strength, the values being 3.97 ± 0.01 and 2.31 ± 0.01.  相似文献   

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