Drug-receptor interaction plays an important role in a series of biological effects, such as cell pro- liferation, immune response, tumor metastasis, and drug delivery. Therefore, the research on drug-re- ceptor inter...Drug-receptor interaction plays an important role in a series of biological effects, such as cell pro- liferation, immune response, tumor metastasis, and drug delivery. Therefore, the research on drug-re- ceptor interaction is growing rapidly. The equilibrium dissociation constant （KD） is the basic parameter to evaluate the binding property of the drug-receptor. Thus, a variety of analytical methods have been established to determine the KD values, including radioligand binding assay, surface plasmon resonance method, fluorescence energy resonance transfer method, affinity chromatography, and isothermal ti- tration calorimetry. With the invention and innovation of new technology and analysis method, there is a deep exploration and comprehension about drug-receptor interaction. This review discusses the differ- ent methods of determining the KD values, and analyzes the applicability and the characteristic of each analytical method. Conclusively, the aim is to provide the guidance for researchers to utilize the most appropriate analytical tool to determine the KD values.展开更多
The binding of Tb 3+ to chicken apoovotransferrin was studied by monitoring the fluorescent intensity of Tb 3+ at 549 nm. The conditional equilibrium constants for the complexation of Tb 3+ by chicken apoovotransferri...The binding of Tb 3+ to chicken apoovotransferrin was studied by monitoring the fluorescent intensity of Tb 3+ at 549 nm. The conditional equilibrium constants for the complexation of Tb 3+ by chicken apoovotransferrin in 0 1 mol/L hepes, at pH 7 4 and room temperature were measured. The successive macroscopic binding constants are lg K 1=9 08±0 12 and lg K 2=7 36±0 22. The molar fluorescence enhancement of Tb 3+ apoovotransferrin complex is (2 06±0 14)×10 4 mol -1 ·L. The fluorescence quenching experiment and the titration of N terminal monoferric ovotransferrin showed that Tb 3+ has a preference for being bound to the N terminal binding site of apoovotransferrin.展开更多
A simple and selective ultra performance liquid chromatography--electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） assay was developed for the determination of the human plasma protein binding of four...A simple and selective ultra performance liquid chromatography--electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） assay was developed for the determination of the human plasma protein binding of four bioactive ftavonoids （such as orientin and vitexin） in Polygonum orientale. Protein precipitation was used for sample preparation. Equilibrium dialysis technique was applied to determine the plasma protein binding under physiological conditions. The separation was achieved through a Waters C i s column with a mobile phase composed of 0.1% formic acid in acetonitrile and 0.1% aqueous formic acid using step gradient elution at a flow rate of 0.35 mL/min. A Waters ACQUITYTM TQD system was operated under the multiple reaction monitoring （MRM） mode of positive electrospray ionization. All of the recovery, precision, accuracy and stability of the method met the requirements. Good correlations （r 〉 0.99） of the four compounds were found, which suggested that these compounds can be simultaneously determined with acceptable accuracy. Results showed that the plasma protein bindings of the four bioactive flavonoids were in the range of 74-89% over the six concentrations studied. The binding parameters containing protein binding affinity, protein binding dissociation constant, and protein binding site were studied. The maximum ability to bind with protein was also determined in the assay in order to understand the drug-protein binding of each compound better.展开更多
Sevelamer Carbonate is a crossolinked polymeric amine, it is the active ingredient in Renvela Tablets. Sevelamer Carbonate is indicated for the control of hyperphosphatamiea in patients with end-stage renal disease. T...Sevelamer Carbonate is a crossolinked polymeric amine, it is the active ingredient in Renvela Tablets. Sevelamer Carbonate is indicated for the control of hyperphosphatamiea in patients with end-stage renal disease. The binding parameter constants of Sevelamer Carbonate were determined using the Langmuir approximation for the dosage form at pH 4.0 and 7.0 by Ion Chromatography. An Ion Chromatogrpahy method has been developed to estimate free phosphate in in-vitro phosphate binding study of Sevelamer Carbonate Tablets. The method is selective and capable of detecting phosphate in the presence of placebo matrix. The method has been validated with a lower limit of quantitation of 0.2 mM for Phosphate. A linear response function was established in the range of concentrations 0.2 - 30.0 mM (r > 0.99) for Phosphate. The intra and inter day precision values for Phosphate met the acceptance as per Food and Drug Administrations guidelines. Phosphate was stable in the set of stability studies viz. bench-top and autosampler. The developed method was applied to in-vitro phosphate binding studies of Sevelamer Carbonate Tablets.展开更多
Sevelamer Hydrochloride is a crossolinked polymeric amine;it is the active ingredient in Renagel Tablets. Sevelamer Hydrochloride is indicated for the control of hyperphosphatamiea in patients with end-stage renal dis...Sevelamer Hydrochloride is a crossolinked polymeric amine;it is the active ingredient in Renagel Tablets. Sevelamer Hydrochloride is indicated for the control of hyperphosphatamiea in patients with end-stage renal disease. The binding parameter constants of Sevelamer Hydrochloride were determined using the Langmuir approximation for the dosage form at pH 4.0 and 7.0 by Inductively Coupled Plasma-Optical Emission Spectrometry. An ICP-OES method has been developed to estimate free phosphate in In-Vitro phosphate binding study of Sevelamer HCl Tablets. The method is selective and capable of detecting phosphate in the presence of placebo matrix. The method has been validated with a lower limit of quantitation of 0.2 mM for Phosphate. A linear response function was established for the range of concentrations 0.2 - 25.0 mM (r > 0.99) for Phosphate. The intra and inter day precision values for Phosphate met the acceptance as per Food and Drug Administrations guidelines. Phosphate was stable in the set of stability studies viz. bench-top and autosampler. The developed method was applied to in-vitro phosphate binding studies of Sevelamer HCl Tablets.展开更多
A new method is proposed for determining the composition and stability constant of coordination compounds of the form M m R n ; it can be used to differentiate mono and poly nuclear coordination compounds. ...A new method is proposed for determining the composition and stability constant of coordination compounds of the form M m R n ; it can be used to differentiate mono and poly nuclear coordination compounds. The equation derived is lg( A i/(A max - A i) m)=n lg c′ R+lg( m·β(c M/A max ) ( m -1) ). The method is based on Bent French limited logarithm method. The demonstration of the proposed method has yielded correct results for Sc 3+ chlorophosphonazo Ⅲ system and Fe 3+ Chromazurol S system.展开更多
Mixed rare earth nitrates （REi（NO3）3） in the aqueous solution was mixed with tri-n-butyl phosphate （TBP, （n-C4H9O）3PO） dissolved in kerosene for the formation of their corresponding complexes （REi（NO3）3...Mixed rare earth nitrates （REi（NO3）3） in the aqueous solution was mixed with tri-n-butyl phosphate （TBP, （n-C4H9O）3PO） dissolved in kerosene for the formation of their corresponding complexes （REi（NO3）3·ni（n-C4H9O）3PO） at 303 K. The effects of initial concentrations of both TBP and mixed rare earth nitrates on the equilibrium constants of their complex formations were investigated. The complexes were formed almost immediately after mixing. The simultaneous formations reached their chemical equilibria within a few minutes by shaking the mixture at 200 r/min. The chemical equilibrium constants of the complex formations were independent of the initial TBP concentrations. However, they were decreased by reducing the concentration of REi（NO3）3. All equilibrium constants of the simultaneous complex formations were less than 0.7, while the average molar ratio of TBP to REi（NO3）3 of the complexes varied between 1.0 and 1.6. The chemical equilibrium constant for the formation of La（NO3）3·（n-C4H9O）3PO was 0.09, while that of Dy（NO3）3·（n-C4H9O）3PO was 0.68. The ascending sequence of chemical equilibrium constants for the simultaneous formations was La, Ce, Pr, Nd, Eu, Y, Sm, Gd, and Dy.展开更多
An idea on interfacial equilibrium-potential differences () which are generated for the extraction of univalent metal picrate (MPic) and divalent ones (MPic2) by crown ethers (L) into high-polar diluents was improved....An idea on interfacial equilibrium-potential differences () which are generated for the extraction of univalent metal picrate (MPic) and divalent ones (MPic2) by crown ethers (L) into high-polar diluents was improved. These potentials were clarified with some experimental extraction-data reported before on the M = Ag(I), Ca(II), Sr(II) and Ba(II) extraction with 18-crown-6 ether (18C6) and benzo-18C6 into 1,2-dichloroethane (DCE) and nitrobenzene (NB). Consequently, it was demonstrated that the? values from the extraction-experimentally obtained logKD,Pic ones are in agreement with or close to those calculated from charge balance equations in many cases, where the symbol, KD,Pic, denotes an individual distribution constant of Pic﹣ into the DCE or NB phase. Also, it was experimentally shown that extraction constants based on the overall extraction equilibria do not virtually contain the? terms in their functional expressions.展开更多
Binding kinetic properties of protein–ligand complexes are crucial factors affecting the drug potency.Nevertheless,the current in silico techniques are insufficient in providing accurate and robust predictions for bi...Binding kinetic properties of protein–ligand complexes are crucial factors affecting the drug potency.Nevertheless,the current in silico techniques are insufficient in providing accurate and robust predictions for binding kinetic properties.To this end,this work develops a variety of binding kinetic models for predicting a critical binding kinetic property,dissociation rate constant,using eight machine learning(ML)methods(Bayesian Neural Network(BNN),partial least squares regression,Bayesian ridge,Gaussian process regression,principal component regression,random forest,support vector machine,extreme gradient boosting)and the descriptors of the van der Waals/electrostatic interaction energies.These eight models are applied to two case studies involving the HSP90 and RIP1 kinase inhibitors.Both regression results of two case studies indicate that the BNN model has the state-of-the-art prediction accuracy(HSP90:R^(2)_(test)=0:947,MAE_(test)=0.184,rtest=0.976,RMSE_(test)=0.220;RIP1 kinase:R^(2)_(test)=0:745,MAE_(test)=0.188,rtest=0.961,RMSE_(test)=0.290)in comparison with other seven ML models.展开更多
Although enantiomers of 2-phenylpropionic acids (2-PPAs), or profens are important group of nonsteroidal anti-inflammatory drugs (NSAIDs) and have been in clinical use for many years, there is no literature covering i...Although enantiomers of 2-phenylpropionic acids (2-PPAs), or profens are important group of nonsteroidal anti-inflammatory drugs (NSAIDs) and have been in clinical use for many years, there is no literature covering its binding interaction in particular with cyclodextrins. NSAIDs are marketed as racemates, chiral discrimination and knowledge of enantiomeric bioavailability is essential. Circular dichroism (CD) spectroscopy is the technique of choice for elucidating chirality and monitoring and characterizing molecular recognition phenomena in solution. Methods em-ploying the fundamentals of the simultaneous measurements of absorbance and CD and a novel efficient titration method have been developed to study the binding of β-Cyclodextrin (β-CyD) and the two enantiomers of 2-PPA as a function of pH. The effect on physicochemical properties and bioavailability was investigated. The binding constant, stoichiometry and pKa for both the free and the bound drugs were determined using a Levenburg-Marquadt non-linear equation. The exact nature of the enantiomer discriminating interactions by cyclodextrins (CyDs) is not well understood. In this work, the interactions and co-conformations of both enantiomers of 2-PPA with β-CyD were explained and es-timated using spectroscopic variations upon complexation. The results indicated a change in the physicochemical prop-erties of 2-PPAs upon complexation and highlighted the enantioselective binding of β-CyD as a function of pH. The charge on the vip molecule and its stereochemistry are of great importance in regulating the stability of the vip/β-CyD complexes;hence the bioavailability of drugs. This work elucidates 2-PPAs/β-CyD binding interactions and highlights the effect of β-CyD on drugs with an effective novel method for binding titration and the potential of the simultaneous measurements of absorbance and CD in future chiral drug interactions studies.展开更多
The thermodynamic properties of the most important NaOH-NaAI（OH）4-H20 system in Bayer process for alumina production were investigated. A theoretical model for calculating the equilibrium constant of gibbsite dissol...The thermodynamic properties of the most important NaOH-NaAI（OH）4-H20 system in Bayer process for alumina production were investigated. A theoretical model for calculating the equilibrium constant of gibbsite dissolved in sodium hydroxide solution was proposed. New Pitzer model parameters and mixing parameters for the system NaOH-NaAI（OH）4-H20 were yielded and tested in the temperature range of 298.15-373.15 K. The results show that the proposed model for calculating the equilibrium constant of gibbsite dissolution is applicable and accurate. The obtained Pitzer model parameters of β（0）（NaAl（OH）4）、β（1）（NaAl（OH）4）和CΦ（NaAl（OH）4）,Al（OH）4 for NaAI（OH）4, the binary mixing parameter of θ（OH-Al（OH）4-） with OH-, and the ternary mixing parameter of ψ（Na＋OH-Al（OH）4-） for AI（OH）4- with OH- and Na＋ are temperature-dependent. The prediction of the equilibrium solubility of gibbsite dissolved in sodium hydroxide solution was feasible in the temperature range of 298.15-373.15 K.展开更多
Structural characteristics and proton binding properties of sub-fractions（FA3–FA13） of fulvic acid（FA）, eluted stepwise by pyrophosphate buffer were examined by use of fluorescence titration combined with fluores...Structural characteristics and proton binding properties of sub-fractions（FA3–FA13） of fulvic acid（FA）, eluted stepwise by pyrophosphate buffer were examined by use of fluorescence titration combined with fluorescence regional integration（FRI） and differential fluorescence spectroscopy（DFS）. Humic-like（H-L） and fulvic-like（F-L） materials, which accounted for more than 80% of fluorescence response, were dominant in five sub-fractions of FA. Based on FRI analysis, except the response of F-L materials in FA9 and FA13, maximum changes in percent fluorescence response were less than 10% as pH was increased from 2.5 to 11.5.Contents of carboxylic and phenolic groups were compared for fluorescence peaks of FA sub-fractions based on pH-dependent fluorescence derived from DFS. Static quenching was the dominant mechanism for binding of protons by FA sub-fractions. Dissociation constants（p Ka） were calculated by use of results of DFS and the modified Stern-Volmer relationship. The p Kaof H-L, F-L, tryptophan-like and tyrosine-like materials of FA subfractions exhibited ranges of 3.17–4.06, 3.12–3.97, 4.14–4.45 and 4.25–4.76, respectively, for acidic pHs. At basic pHs, values of p Ka for corresponding materials were in ranges of 9.71–10.24, 9.62–10.99, 9.67–10.31 and 9.33–10.28, respectively. At acidic pH, protein-like（P-L）materials had greater affinities for protons than did either H-L or F-L materials. The dicarboxylic and phenolic groups were likely predominant sites of protonation for both H-L and F-L materials at both acidic and basic pHs. Amino acid groups were significant factors during proton binding to protein-like materials of FA sub-fractions at basic pH.展开更多
Equilibrium constants are essential for understanding and predicting the behavior of chemical systems across various scientifc disciplines.Traditionally,these constants are computed via nonlinear regression of reactio...Equilibrium constants are essential for understanding and predicting the behavior of chemical systems across various scientifc disciplines.Traditionally,these constants are computed via nonlinear regression of reaction isotherms,which show the depend-ence of the unreacted fraction of one reactant on the total concentration of another reactant.However,while these equilibrium constants can be precise(with small random errors),they may also be grossly inaccurate(with large systematic errors),leading to potential misinterpretations.Although some statisticalmethods exist for assessing the accuracy of nonlinear regression,their limitedpracticality for molecular scientists has resulted in their neglect by this research community.The objective of this work is to develop a practical method for quantitatively assessing the accuracy of equilibrium constants that could be easily understood and immediately adopted by researchers routinely determining these constants.Our approach integrates error-propagation and regression-stability analyses to establish the accuracy confidence interval(ACI)-a range within which the true value of the computed parameter lies with a defined probability.In a proof-of-principle study,we applied this approach to develop a workflow for determining the ACI of the equilibrium dissociation constant(K_(d))of affinity complexes from a single binding isotherm.We clearly explained how the input parameters for this workflow can be determined,and finally,we have implemented this workflow in a user-friendly web application(https://aci.sci.yorku.ca)to facilitate its immediate adoption by molecular scientists,regardless of their mathematical and computer proficiency.We further conducted three case studies exemplifying the use of the ACI in the context of simultaneous assessment of precision and accuracy of determined K_(d)values.By understanding the ACI of equilibrium constants and other parameters computed through nonlinear regression,researchers can avoid misconceptions that arise from relying solely on precision.展开更多
The binding constant（KDOM） of pyrene onto different molecular weight（Mw） fractions of a dissolved organic matter（DOM） extract from an estuarine sediment was measured via a fluorescence quenching method,and the p...The binding constant（KDOM） of pyrene onto different molecular weight（Mw） fractions of a dissolved organic matter（DOM） extract from an estuarine sediment was measured via a fluorescence quenching method,and the possible binding mechanisms were discussed.The influence of water chemical parameters on pyrene binding was studied to elucidate the effects of DOM steric conformation.DOM fraction with larger M w（14000） showed a greater KDOM（2.02×10 5） than that with smaller Mw did,and the KDOMs were 1.16×105 and 1.13×105 for the fractions with M w of 1000―14000 and 1000,respectively.The K DOM s of different M w DOM fractions were correlated positively with the atomic ratio of C/H and absorbance at 280 nm;while a negative correlation existed between K DOM and（O＋C）/N（atomic ratio）,and K DOM and O-containing groups.These correlations indicate the positive influence of aromatic structure and the negative effect of polarity on DOM binding capacity.Infrared spectroscopy revealed that specific interactions existed between pyrene and the DOM fraction with larger M W besides hydrophobic partition,i.e.,NH-π interaction in DOM moiety（1000―14000） and π-π electron donor acceptor（EDA） forces in DOM moiety（14000）.KDOM varied in a complex pattern with increasing cation concentration and pH,which could be explained by the change in DOM steric conformation.Formed aggregates favored the lipophilic partition of pyrene.However,the accessibility to some interior binding sites became low when the aggregate was too large,leading to a reduced KDOM.展开更多
Soil-water characteristics of Gaomiaozi(GMZ)Ca-bentonite at high suctions(3–287MPa)are measured by vapour equilibrium technique.The soil-water retention curve(SWRC)of samples with the same initial compaction states i...Soil-water characteristics of Gaomiaozi(GMZ)Ca-bentonite at high suctions(3–287MPa)are measured by vapour equilibrium technique.The soil-water retention curve(SWRC)of samples with the same initial compaction states is obtained in drying and wetting process.At high suctions,the hysteresis behaviour is not obvious in relationship between water content and suction,while the opposite holds between degree of saturation and suction.The suction variation can change its water retention behaviour and void ratio.Moreover,changes of void ratio can bring about changes in degree of saturation.Therefore,the total change in degree of saturation includes changes caused by suction and that by void ratio.In the space of degree of saturation and suction,the SWRC at constant void ratio shifts to the direction of higher suctions with decreasing void ratio.However,the relationship between water content and suction is less affected by changes of void ratio.The degree of saturation decreases approximately linearly with increasing void ratio at a constant suction.Moreover,the slope of the line decreases with increasing suction and they show an approximately linear relationship in semi-logarithmical scale.From this linear relationship,the variation of degree of saturation caused by the change in void ratio can be obtained.Correspondingly,SWRC at a constant void ratio can be determined from SWRC at different void ratios.展开更多
The geometry and binding interaction of M+CO2 (M represents the firstrow transition metals) were studied using ab initio methods. In some cases the frequency calculations and basis set superposition error corrections ...The geometry and binding interaction of M+CO2 (M represents the firstrow transition metals) were studied using ab initio methods. In some cases the frequency calculations and basis set superposition error corrections were included. For all the complexes under the study, the linear structures were found to be the equilibrium structure. The distances of M+—O in R(M+—O) in which M has 4s electrons are obvious longer than those in which M has no 4s electrons, and from Sc to Zn the change trend is decreased, accompanied with some oscillation. The binding energy has an opposite change trend to that of the R(M+—O). Linear M+CO2 has the same spin as M+, while Tshape structures may have different spins. The static electronic interaction was found to be about 80% of the total binding energy.展开更多
The interaction of baicalein with bovine serum albumin（BSA） was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of...The interaction of baicalein with bovine serum albumin（BSA） was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of 10~5 M^（-1） from fluorescence quenching studies.Negative ΔH°（-5.66 ＋ 0.14 kJ/mol） and positive（ΔS°）（＋ 79.96 ＋ 0.65J/mol K） indicate the presence of electrostatic interactions along with the hydrophobic forces that result in a positive ΔS°.The hydrophobic association of baicalein with BSA diminishes in the presence of sodium dodecyl sulfate（SDS） due to probable hydrophobic association of baicalein with SDS,resulting in a negative ΔS°（-40.65 ＋ 0.87 J/mol K）.Matrix-assisted laser desorption ionization/time of flight（MALDI-TOF） experiments indicate a 1：1 complexation between baicalein and BSA.The unfolding and refolding phenomena of BSA were investigated in the absence and presence of baicalein using steady-state and fluorescence lifetime measurements.It was observed that the presence of urea ruptured the non-covalent interaction between baicalein and BSA.The presence of metal ions（Ag~＋,Mg^（2＋）,Ni^（2＋）,Mn^（2＋）,Co^（2＋） and Zn^（2＋）） increased the binding affinity of ligand towards BSA.The changes in conformational aspects of BSA after ligand binding were also investigated using circular dichroism（CD） and Fourier transform infrared（FT-IR） spectroscopic techniques.Site selectivity studies following molecular docking analyses indicated the binding of baicalein to site 1（subdomain MA） of BSA.展开更多
The parasite Plasmodium falciparum is responsible for the major world scourge malaria, a disease that affects 3.3 billion people worldwide. The development of new drugs is critical because of the diminished effectiven...The parasite Plasmodium falciparum is responsible for the major world scourge malaria, a disease that affects 3.3 billion people worldwide. The development of new drugs is critical because of the diminished effectiveness of current antimalarial agents mainly due to parasitic resistance, side effects and cost. Molecular docking was used to explore structural motifs responsible for the interactions between triose phosphate isomerase (TPI), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and aldolase (ALD) from human and Plasmodium cells with 8 novel sufonylamide derivatives. All the ligands modeled, interact with all three enzymes in the micromolar range. The top ligand (sulfaE) shows a 70-fold increase in selective binding to pfTPI compared to hTPI (dissociation constant-KI of 7.83 μM and 0.177 μM for hTPI and pfTPI respectively), on par with antimalarial drug chloroquine.ALD and GAPDH form complexes with similar binding sites, comprising amino acids of similar chemical properties and polarities. Human TPI and pfTPI bind sulfonamide derivatives using two distinct binding sites and residues. Key residues at the dimer interface of pfTPI (VAL44, SER45, TYR48, GLN64, ASN65, VAL78) form a tight pocket with favorable polar contacts. The affinity with TPI is the most specific, stable, and selective suggesting pfTPI is a candidate for development of antimalarial drugs.展开更多
The thermal analysis of precise thermophysical data for pure fluids from electronic databases is developed to investigate the molecular interaction mechanisms and parameters and the structural features of heterogeneit...The thermal analysis of precise thermophysical data for pure fluids from electronic databases is developed to investigate the molecular interaction mechanisms and parameters and the structural features of heterogeneities in fluids. The method is based on the series expansion of thermophysical values by powers of the monomer fraction density. Unlike the virial expansion by powers of the total density, the series expansion terms in this method directly reflect properties of the corresponding cluster fractions. The internal energy had been selected among thermophysical properties as the most informative for this method. The thermal analysis of its series expansion coefficients permits to estimate the temperature dependence of the pair bond parameters, the clusters’ bond energies and equilibrium constants, the structural transitions between dominating isomers of clusters. The application of method to different pure fluids, including noble and molecular gases with van der Waals and polar molecular interactions, brings unknown clusters’ characteristics for the fluids under investigation. The thermal analysis of the ordinary and heavy Water vapors points on no trivial isotopic effects. The unpredictable growth of the pair bond energy with temperature in Alkanes points on existence in hydrocarbons of some unknown molecular interaction forces in addition to dispersion forces.展开更多
The equilibrium of Mg-S in Ni melt was studied by the method of vapour equilibrium in a sealed chamber.At 1530℃ the equilibrium constant of the reaction MgS_(s)=Mg_(Ni)+S_(Ni)and the activity interaction coefficient ...The equilibrium of Mg-S in Ni melt was studied by the method of vapour equilibrium in a sealed chamber.At 1530℃ the equilibrium constant of the reaction MgS_(s)=Mg_(Ni)+S_(Ni)and the activity interaction coefficient were determined as K_(MgS)=6.76×10^(-5)and e_S^(Mg)=-9.1.展开更多
文摘Drug-receptor interaction plays an important role in a series of biological effects, such as cell pro- liferation, immune response, tumor metastasis, and drug delivery. Therefore, the research on drug-re- ceptor interaction is growing rapidly. The equilibrium dissociation constant （KD） is the basic parameter to evaluate the binding property of the drug-receptor. Thus, a variety of analytical methods have been established to determine the KD values, including radioligand binding assay, surface plasmon resonance method, fluorescence energy resonance transfer method, affinity chromatography, and isothermal ti- tration calorimetry. With the invention and innovation of new technology and analysis method, there is a deep exploration and comprehension about drug-receptor interaction. This review discusses the differ- ent methods of determining the KD values, and analyzes the applicability and the characteristic of each analytical method. Conclusively, the aim is to provide the guidance for researchers to utilize the most appropriate analytical tool to determine the KD values.
文摘The binding of Tb 3+ to chicken apoovotransferrin was studied by monitoring the fluorescent intensity of Tb 3+ at 549 nm. The conditional equilibrium constants for the complexation of Tb 3+ by chicken apoovotransferrin in 0 1 mol/L hepes, at pH 7 4 and room temperature were measured. The successive macroscopic binding constants are lg K 1=9 08±0 12 and lg K 2=7 36±0 22. The molar fluorescence enhancement of Tb 3+ apoovotransferrin complex is (2 06±0 14)×10 4 mol -1 ·L. The fluorescence quenching experiment and the titration of N terminal monoferric ovotransferrin showed that Tb 3+ has a preference for being bound to the N terminal binding site of apoovotransferrin.
基金This work was supported by the National Science Foundation of China （No. 30860366） Guizhou Province Municipal Science and Technology Project （No. 2007-6010）.
文摘A simple and selective ultra performance liquid chromatography--electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） assay was developed for the determination of the human plasma protein binding of four bioactive ftavonoids （such as orientin and vitexin） in Polygonum orientale. Protein precipitation was used for sample preparation. Equilibrium dialysis technique was applied to determine the plasma protein binding under physiological conditions. The separation was achieved through a Waters C i s column with a mobile phase composed of 0.1% formic acid in acetonitrile and 0.1% aqueous formic acid using step gradient elution at a flow rate of 0.35 mL/min. A Waters ACQUITYTM TQD system was operated under the multiple reaction monitoring （MRM） mode of positive electrospray ionization. All of the recovery, precision, accuracy and stability of the method met the requirements. Good correlations （r 〉 0.99） of the four compounds were found, which suggested that these compounds can be simultaneously determined with acceptable accuracy. Results showed that the plasma protein bindings of the four bioactive flavonoids were in the range of 74-89% over the six concentrations studied. The binding parameters containing protein binding affinity, protein binding dissociation constant, and protein binding site were studied. The maximum ability to bind with protein was also determined in the assay in order to understand the drug-protein binding of each compound better.
文摘Sevelamer Carbonate is a crossolinked polymeric amine, it is the active ingredient in Renvela Tablets. Sevelamer Carbonate is indicated for the control of hyperphosphatamiea in patients with end-stage renal disease. The binding parameter constants of Sevelamer Carbonate were determined using the Langmuir approximation for the dosage form at pH 4.0 and 7.0 by Ion Chromatography. An Ion Chromatogrpahy method has been developed to estimate free phosphate in in-vitro phosphate binding study of Sevelamer Carbonate Tablets. The method is selective and capable of detecting phosphate in the presence of placebo matrix. The method has been validated with a lower limit of quantitation of 0.2 mM for Phosphate. A linear response function was established in the range of concentrations 0.2 - 30.0 mM (r > 0.99) for Phosphate. The intra and inter day precision values for Phosphate met the acceptance as per Food and Drug Administrations guidelines. Phosphate was stable in the set of stability studies viz. bench-top and autosampler. The developed method was applied to in-vitro phosphate binding studies of Sevelamer Carbonate Tablets.
文摘Sevelamer Hydrochloride is a crossolinked polymeric amine;it is the active ingredient in Renagel Tablets. Sevelamer Hydrochloride is indicated for the control of hyperphosphatamiea in patients with end-stage renal disease. The binding parameter constants of Sevelamer Hydrochloride were determined using the Langmuir approximation for the dosage form at pH 4.0 and 7.0 by Inductively Coupled Plasma-Optical Emission Spectrometry. An ICP-OES method has been developed to estimate free phosphate in In-Vitro phosphate binding study of Sevelamer HCl Tablets. The method is selective and capable of detecting phosphate in the presence of placebo matrix. The method has been validated with a lower limit of quantitation of 0.2 mM for Phosphate. A linear response function was established for the range of concentrations 0.2 - 25.0 mM (r > 0.99) for Phosphate. The intra and inter day precision values for Phosphate met the acceptance as per Food and Drug Administrations guidelines. Phosphate was stable in the set of stability studies viz. bench-top and autosampler. The developed method was applied to in-vitro phosphate binding studies of Sevelamer HCl Tablets.
文摘A new method is proposed for determining the composition and stability constant of coordination compounds of the form M m R n ; it can be used to differentiate mono and poly nuclear coordination compounds. The equation derived is lg( A i/(A max - A i) m)=n lg c′ R+lg( m·β(c M/A max ) ( m -1) ). The method is based on Bent French limited logarithm method. The demonstration of the proposed method has yielded correct results for Sc 3+ chlorophosphonazo Ⅲ system and Fe 3+ Chromazurol S system.
文摘Mixed rare earth nitrates （REi（NO3）3） in the aqueous solution was mixed with tri-n-butyl phosphate （TBP, （n-C4H9O）3PO） dissolved in kerosene for the formation of their corresponding complexes （REi（NO3）3·ni（n-C4H9O）3PO） at 303 K. The effects of initial concentrations of both TBP and mixed rare earth nitrates on the equilibrium constants of their complex formations were investigated. The complexes were formed almost immediately after mixing. The simultaneous formations reached their chemical equilibria within a few minutes by shaking the mixture at 200 r/min. The chemical equilibrium constants of the complex formations were independent of the initial TBP concentrations. However, they were decreased by reducing the concentration of REi（NO3）3. All equilibrium constants of the simultaneous complex formations were less than 0.7, while the average molar ratio of TBP to REi（NO3）3 of the complexes varied between 1.0 and 1.6. The chemical equilibrium constant for the formation of La（NO3）3·（n-C4H9O）3PO was 0.09, while that of Dy（NO3）3·（n-C4H9O）3PO was 0.68. The ascending sequence of chemical equilibrium constants for the simultaneous formations was La, Ce, Pr, Nd, Eu, Y, Sm, Gd, and Dy.
文摘An idea on interfacial equilibrium-potential differences () which are generated for the extraction of univalent metal picrate (MPic) and divalent ones (MPic2) by crown ethers (L) into high-polar diluents was improved. These potentials were clarified with some experimental extraction-data reported before on the M = Ag(I), Ca(II), Sr(II) and Ba(II) extraction with 18-crown-6 ether (18C6) and benzo-18C6 into 1,2-dichloroethane (DCE) and nitrobenzene (NB). Consequently, it was demonstrated that the? values from the extraction-experimentally obtained logKD,Pic ones are in agreement with or close to those calculated from charge balance equations in many cases, where the symbol, KD,Pic, denotes an individual distribution constant of Pic﹣ into the DCE or NB phase. Also, it was experimentally shown that extraction constants based on the overall extraction equilibria do not virtually contain the? terms in their functional expressions.
基金financial supports of“the Fundamental Research Funds for the Central Universities”(DUT22YG218),NSFC(22278053,22078041)China Postdoctoral Science Foundation(2022M710578)“the Dalian High-level Talents Innovation Support Program”(2021RQ105).
文摘Binding kinetic properties of protein–ligand complexes are crucial factors affecting the drug potency.Nevertheless,the current in silico techniques are insufficient in providing accurate and robust predictions for binding kinetic properties.To this end,this work develops a variety of binding kinetic models for predicting a critical binding kinetic property,dissociation rate constant,using eight machine learning(ML)methods(Bayesian Neural Network(BNN),partial least squares regression,Bayesian ridge,Gaussian process regression,principal component regression,random forest,support vector machine,extreme gradient boosting)and the descriptors of the van der Waals/electrostatic interaction energies.These eight models are applied to two case studies involving the HSP90 and RIP1 kinase inhibitors.Both regression results of two case studies indicate that the BNN model has the state-of-the-art prediction accuracy(HSP90:R^(2)_(test)=0:947,MAE_(test)=0.184,rtest=0.976,RMSE_(test)=0.220;RIP1 kinase:R^(2)_(test)=0:745,MAE_(test)=0.188,rtest=0.961,RMSE_(test)=0.290)in comparison with other seven ML models.
文摘Although enantiomers of 2-phenylpropionic acids (2-PPAs), or profens are important group of nonsteroidal anti-inflammatory drugs (NSAIDs) and have been in clinical use for many years, there is no literature covering its binding interaction in particular with cyclodextrins. NSAIDs are marketed as racemates, chiral discrimination and knowledge of enantiomeric bioavailability is essential. Circular dichroism (CD) spectroscopy is the technique of choice for elucidating chirality and monitoring and characterizing molecular recognition phenomena in solution. Methods em-ploying the fundamentals of the simultaneous measurements of absorbance and CD and a novel efficient titration method have been developed to study the binding of β-Cyclodextrin (β-CyD) and the two enantiomers of 2-PPA as a function of pH. The effect on physicochemical properties and bioavailability was investigated. The binding constant, stoichiometry and pKa for both the free and the bound drugs were determined using a Levenburg-Marquadt non-linear equation. The exact nature of the enantiomer discriminating interactions by cyclodextrins (CyDs) is not well understood. In this work, the interactions and co-conformations of both enantiomers of 2-PPA with β-CyD were explained and es-timated using spectroscopic variations upon complexation. The results indicated a change in the physicochemical prop-erties of 2-PPAs upon complexation and highlighted the enantioselective binding of β-CyD as a function of pH. The charge on the vip molecule and its stereochemistry are of great importance in regulating the stability of the vip/β-CyD complexes;hence the bioavailability of drugs. This work elucidates 2-PPAs/β-CyD binding interactions and highlights the effect of β-CyD on drugs with an effective novel method for binding titration and the potential of the simultaneous measurements of absorbance and CD in future chiral drug interactions studies.
基金Project (2005CB6237) supported by the National Basic Research Program of China
文摘The thermodynamic properties of the most important NaOH-NaAI（OH）4-H20 system in Bayer process for alumina production were investigated. A theoretical model for calculating the equilibrium constant of gibbsite dissolved in sodium hydroxide solution was proposed. New Pitzer model parameters and mixing parameters for the system NaOH-NaAI（OH）4-H20 were yielded and tested in the temperature range of 298.15-373.15 K. The results show that the proposed model for calculating the equilibrium constant of gibbsite dissolution is applicable and accurate. The obtained Pitzer model parameters of β（0）（NaAl（OH）4）、β（1）（NaAl（OH）4）和CΦ（NaAl（OH）4）,Al（OH）4 for NaAI（OH）4, the binary mixing parameter of θ（OH-Al（OH）4-） with OH-, and the ternary mixing parameter of ψ（Na＋OH-Al（OH）4-） for AI（OH）4- with OH- and Na＋ are temperature-dependent. The prediction of the equilibrium solubility of gibbsite dissolved in sodium hydroxide solution was feasible in the temperature range of 298.15-373.15 K.
基金supported by the National Natural Science Foundation of China(Nos.41173084,41521003,41573130,41630645,41703115 and 41503104)the Beijing Natural Science Foundation(No.8162044)the Canada Research Chair program,Einstein Professor Program of the Chinese Academy of Sciences,and the High Level Foreign Experts Program(#GDT20143200016)
文摘Structural characteristics and proton binding properties of sub-fractions（FA3–FA13） of fulvic acid（FA）, eluted stepwise by pyrophosphate buffer were examined by use of fluorescence titration combined with fluorescence regional integration（FRI） and differential fluorescence spectroscopy（DFS）. Humic-like（H-L） and fulvic-like（F-L） materials, which accounted for more than 80% of fluorescence response, were dominant in five sub-fractions of FA. Based on FRI analysis, except the response of F-L materials in FA9 and FA13, maximum changes in percent fluorescence response were less than 10% as pH was increased from 2.5 to 11.5.Contents of carboxylic and phenolic groups were compared for fluorescence peaks of FA sub-fractions based on pH-dependent fluorescence derived from DFS. Static quenching was the dominant mechanism for binding of protons by FA sub-fractions. Dissociation constants（p Ka） were calculated by use of results of DFS and the modified Stern-Volmer relationship. The p Kaof H-L, F-L, tryptophan-like and tyrosine-like materials of FA subfractions exhibited ranges of 3.17–4.06, 3.12–3.97, 4.14–4.45 and 4.25–4.76, respectively, for acidic pHs. At basic pHs, values of p Ka for corresponding materials were in ranges of 9.71–10.24, 9.62–10.99, 9.67–10.31 and 9.33–10.28, respectively. At acidic pH, protein-like（P-L）materials had greater affinities for protons than did either H-L or F-L materials. The dicarboxylic and phenolic groups were likely predominant sites of protonation for both H-L and F-L materials at both acidic and basic pHs. Amino acid groups were significant factors during proton binding to protein-like materials of FA sub-fractions at basic pH.
基金supported by a York University grant to the Catalyzing Interdisciplinary Research Cluster“Technologies for Identification and Control of Infectious Diseases”and an NSERC Discovery Grant(RGPIN-2022-04563)to S.N.KAdditional support was provided by an NSERC Undergraduate Student Research Award(USRA-582491-2023)to J.La University of Münster visiting fellowship to S.N.K.We extend our gratitude to Prof.Howard A.Levin and Dr.Yeon-Jung Seo from Iowa State University and Prof.Jianhong Wu from York University for their valuable assistance in refining the manuscript.
文摘Equilibrium constants are essential for understanding and predicting the behavior of chemical systems across various scientifc disciplines.Traditionally,these constants are computed via nonlinear regression of reaction isotherms,which show the depend-ence of the unreacted fraction of one reactant on the total concentration of another reactant.However,while these equilibrium constants can be precise(with small random errors),they may also be grossly inaccurate(with large systematic errors),leading to potential misinterpretations.Although some statisticalmethods exist for assessing the accuracy of nonlinear regression,their limitedpracticality for molecular scientists has resulted in their neglect by this research community.The objective of this work is to develop a practical method for quantitatively assessing the accuracy of equilibrium constants that could be easily understood and immediately adopted by researchers routinely determining these constants.Our approach integrates error-propagation and regression-stability analyses to establish the accuracy confidence interval(ACI)-a range within which the true value of the computed parameter lies with a defined probability.In a proof-of-principle study,we applied this approach to develop a workflow for determining the ACI of the equilibrium dissociation constant(K_(d))of affinity complexes from a single binding isotherm.We clearly explained how the input parameters for this workflow can be determined,and finally,we have implemented this workflow in a user-friendly web application(https://aci.sci.yorku.ca)to facilitate its immediate adoption by molecular scientists,regardless of their mathematical and computer proficiency.We further conducted three case studies exemplifying the use of the ACI in the context of simultaneous assessment of precision and accuracy of determined K_(d)values.By understanding the ACI of equilibrium constants and other parameters computed through nonlinear regression,researchers can avoid misconceptions that arise from relying solely on precision.
基金Supported by the National Natural Science Foundation of China(Nos.20737002,41073087)
文摘The binding constant（KDOM） of pyrene onto different molecular weight（Mw） fractions of a dissolved organic matter（DOM） extract from an estuarine sediment was measured via a fluorescence quenching method,and the possible binding mechanisms were discussed.The influence of water chemical parameters on pyrene binding was studied to elucidate the effects of DOM steric conformation.DOM fraction with larger M w（14000） showed a greater KDOM（2.02×10 5） than that with smaller Mw did,and the KDOMs were 1.16×105 and 1.13×105 for the fractions with M w of 1000―14000 and 1000,respectively.The K DOM s of different M w DOM fractions were correlated positively with the atomic ratio of C/H and absorbance at 280 nm;while a negative correlation existed between K DOM and（O＋C）/N（atomic ratio）,and K DOM and O-containing groups.These correlations indicate the positive influence of aromatic structure and the negative effect of polarity on DOM binding capacity.Infrared spectroscopy revealed that specific interactions existed between pyrene and the DOM fraction with larger M W besides hydrophobic partition,i.e.,NH-π interaction in DOM moiety（1000―14000） and π-π electron donor acceptor（EDA） forces in DOM moiety（14000）.KDOM varied in a complex pattern with increasing cation concentration and pH,which could be explained by the change in DOM steric conformation.Formed aggregates favored the lipophilic partition of pyrene.However,the accessibility to some interior binding sites became low when the aggregate was too large,leading to a reduced KDOM.
基金the National Natural Sciences Foundation of China (No. 41102163)
文摘Soil-water characteristics of Gaomiaozi(GMZ)Ca-bentonite at high suctions(3–287MPa)are measured by vapour equilibrium technique.The soil-water retention curve(SWRC)of samples with the same initial compaction states is obtained in drying and wetting process.At high suctions,the hysteresis behaviour is not obvious in relationship between water content and suction,while the opposite holds between degree of saturation and suction.The suction variation can change its water retention behaviour and void ratio.Moreover,changes of void ratio can bring about changes in degree of saturation.Therefore,the total change in degree of saturation includes changes caused by suction and that by void ratio.In the space of degree of saturation and suction,the SWRC at constant void ratio shifts to the direction of higher suctions with decreasing void ratio.However,the relationship between water content and suction is less affected by changes of void ratio.The degree of saturation decreases approximately linearly with increasing void ratio at a constant suction.Moreover,the slope of the line decreases with increasing suction and they show an approximately linear relationship in semi-logarithmical scale.From this linear relationship,the variation of degree of saturation caused by the change in void ratio can be obtained.Correspondingly,SWRC at a constant void ratio can be determined from SWRC at different void ratios.
文摘The geometry and binding interaction of M+CO2 (M represents the firstrow transition metals) were studied using ab initio methods. In some cases the frequency calculations and basis set superposition error corrections were included. For all the complexes under the study, the linear structures were found to be the equilibrium structure. The distances of M+—O in R(M+—O) in which M has 4s electrons are obvious longer than those in which M has no 4s electrons, and from Sc to Zn the change trend is decreased, accompanied with some oscillation. The binding energy has an opposite change trend to that of the R(M+—O). Linear M+CO2 has the same spin as M+, while Tshape structures may have different spins. The static electronic interaction was found to be about 80% of the total binding energy.
基金Department of Science and Technology(DST,Project no.SR/SO/BB-54/2007),Government of India for financial support
文摘The interaction of baicalein with bovine serum albumin（BSA） was investigated with the help of spectroscopic and molecular docking studies.The binding affinity of baicalein towards BSA was estimated to be in order of 10~5 M^（-1） from fluorescence quenching studies.Negative ΔH°（-5.66 ＋ 0.14 kJ/mol） and positive（ΔS°）（＋ 79.96 ＋ 0.65J/mol K） indicate the presence of electrostatic interactions along with the hydrophobic forces that result in a positive ΔS°.The hydrophobic association of baicalein with BSA diminishes in the presence of sodium dodecyl sulfate（SDS） due to probable hydrophobic association of baicalein with SDS,resulting in a negative ΔS°（-40.65 ＋ 0.87 J/mol K）.Matrix-assisted laser desorption ionization/time of flight（MALDI-TOF） experiments indicate a 1：1 complexation between baicalein and BSA.The unfolding and refolding phenomena of BSA were investigated in the absence and presence of baicalein using steady-state and fluorescence lifetime measurements.It was observed that the presence of urea ruptured the non-covalent interaction between baicalein and BSA.The presence of metal ions（Ag~＋,Mg^（2＋）,Ni^（2＋）,Mn^（2＋）,Co^（2＋） and Zn^（2＋）） increased the binding affinity of ligand towards BSA.The changes in conformational aspects of BSA after ligand binding were also investigated using circular dichroism（CD） and Fourier transform infrared（FT-IR） spectroscopic techniques.Site selectivity studies following molecular docking analyses indicated the binding of baicalein to site 1（subdomain MA） of BSA.
文摘The parasite Plasmodium falciparum is responsible for the major world scourge malaria, a disease that affects 3.3 billion people worldwide. The development of new drugs is critical because of the diminished effectiveness of current antimalarial agents mainly due to parasitic resistance, side effects and cost. Molecular docking was used to explore structural motifs responsible for the interactions between triose phosphate isomerase (TPI), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and aldolase (ALD) from human and Plasmodium cells with 8 novel sufonylamide derivatives. All the ligands modeled, interact with all three enzymes in the micromolar range. The top ligand (sulfaE) shows a 70-fold increase in selective binding to pfTPI compared to hTPI (dissociation constant-KI of 7.83 μM and 0.177 μM for hTPI and pfTPI respectively), on par with antimalarial drug chloroquine.ALD and GAPDH form complexes with similar binding sites, comprising amino acids of similar chemical properties and polarities. Human TPI and pfTPI bind sulfonamide derivatives using two distinct binding sites and residues. Key residues at the dimer interface of pfTPI (VAL44, SER45, TYR48, GLN64, ASN65, VAL78) form a tight pocket with favorable polar contacts. The affinity with TPI is the most specific, stable, and selective suggesting pfTPI is a candidate for development of antimalarial drugs.
文摘The thermal analysis of precise thermophysical data for pure fluids from electronic databases is developed to investigate the molecular interaction mechanisms and parameters and the structural features of heterogeneities in fluids. The method is based on the series expansion of thermophysical values by powers of the monomer fraction density. Unlike the virial expansion by powers of the total density, the series expansion terms in this method directly reflect properties of the corresponding cluster fractions. The internal energy had been selected among thermophysical properties as the most informative for this method. The thermal analysis of its series expansion coefficients permits to estimate the temperature dependence of the pair bond parameters, the clusters’ bond energies and equilibrium constants, the structural transitions between dominating isomers of clusters. The application of method to different pure fluids, including noble and molecular gases with van der Waals and polar molecular interactions, brings unknown clusters’ characteristics for the fluids under investigation. The thermal analysis of the ordinary and heavy Water vapors points on no trivial isotopic effects. The unpredictable growth of the pair bond energy with temperature in Alkanes points on existence in hydrocarbons of some unknown molecular interaction forces in addition to dispersion forces.
文摘The equilibrium of Mg-S in Ni melt was studied by the method of vapour equilibrium in a sealed chamber.At 1530℃ the equilibrium constant of the reaction MgS_(s)=Mg_(Ni)+S_(Ni)and the activity interaction coefficient were determined as K_(MgS)=6.76×10^(-5)and e_S^(Mg)=-9.1.
