Study of the physicochemical properties of aqueous dantrolene solutions by differential pulse polarography

Dantrolene is a skeletal-muscle relaxant which exists in three different forms over the pH range 0-14, corresponding to the cation H(2)A(+), neutral species HA and anion A(-). Dantrolene is slightly soluble in water and is polarographically reducible over the whole pH range. The acid dissociation constants of the ionic species were investigated by means of differential pulse polarography (H(2)A(+)/HA equilibrium with pK(a1) = 2.02 +/- 0.05) and potentiometry (HA/pK(a2) = 7.49 +/- 0.05). It was shown that differential pulse polarography is a valid alternative method when the pK(a) values of an electroactive drug cannot be determined by potentiometric or spectrophotometric methods. Polarography was also used to monitor the stability of the drug in acidic media and its extraction by chloroform.     

Spectrophotometric determination of the dissociation constants of n.n'-bis(2-hydroxyethyl)dithio-oxamide

The dissociation constants of N, N'-bis(2-hydroxyethyl)dithio-oxamide were determined by a spectrophotometric method. The dissociation constants were calculated by means of a weighted least squares technique. N, N'-Bis(2-hydroxyethyl)dithio-oxamide was found to be a dibasic acid with a thermodynamic dissociation constant pK1-11/04. At ionic strength μ - 0.5, pK1 - 10.71 and pK2 13.92.     

Potentiometric determination of the dissociation constants of an asymmetric sorbent containing l-proline, and the stability constants of its Cu(II) complexes

The dissociation constants of the carboxyl groups (pK(a1) = 2.2, n = 1.8) and amino groups (pK(a2) = 9.5, n(2) = 1.6) of a sorbent prepared by reacting l-proline with a cross-linked chloromethylated styrene polymer have been determined by potentiometric titration. The potentiometrically measured stability constants of the Cu(II) complexes of the resin (logbeta(1) = 6.9 and log beta(2) = 12.4) were found to be close to the values for the Cu(II) complexes of N-benzyl-l-proline. For complexed resins of alpha-amino-acid type the pH-values of decomplexation do not appear to be directly correlated with the stability constants.     

亚甲基二膦酸为配位体的无氰碱性镀铜

提出一种以亚甲基二膦酸(MDPA, H₄L)为主配位剂的无氰镀铜体系. 采用pH 电位滴定法分别测定MDPA的四级解离常数和MDPA-Cu(II)的稳定常数, 并比较MDPA-Cu(II)和羟基乙叉二膦酸(HEDPA)-Cu(II)的循环伏安曲线和阴极极化曲线. 结果表明: MDPA各级解离常数为, pK₁=1.86, pK₂=2.65, pK₃=6.81, pK₄=9.04;MDPA与Cu²⁺形成分级配合物的稳定常数为, pK_ML=10.65, pK_ML2 = 5.59, pK_ML3 = 2.50; 随着pH升高, 形成的配合物依次为, Cu(H₃L)₂、[Cu(H₃L)(H₂L)]-和[Cu(H₂L)₂]^2-; 当pH在7-10 时, MDPA较HEDPA更易与Cu²⁺配位. 当pH=9 时, MDPA碱性镀铜体系阴极主要发生的是[Cu(H₃L)(H₂L)]^-和[Cu(H₂L)₂]^2-还原生成铜的过程; 在10 °C,MDPA体系的铜配位化合物还原生成铜的电位比HEDPA体系负移, 扩散速度更快.     

Potentiometric determination of aminal stability constants

Potentiometric titration was used to determine the logarithms of the stepwise equilibrium constants for the species formed between morpholine and formaldehyde in aqueous solution, ionic strength 0.5 and 2.5M (KCl) at 25 degrees C. The instrumental and computational techniques developed for metal-ligand stability constant determination were applied. Formaldehyde is equivalent to the metal-ion and is represented by M while neutral morpholine is equivalent to the ligand and is represented by L. The stability constants of the following equilibria were determined by non-linear regression (figures in parentheses are at ionic strength 2.5 M KCl): M + L left arrow over right arrow ML (hemi-aminal) logK(1) = 2.90 +/- 0.02 (2.980 +/- 0.004); ML + L left arrow over right arrow ML(2) (bis-aminal); log K(2) = 1.3 +/- 0.2 (1.41 +/- 0.07); MLH left arrow over right arrow ML + H(+) (protonated hemi-aminal) pK(a) = 5.87 +/- 0.01 (6.411 +/- 0.005); ML(2)H left arrow over right arrow ML(2) + H(+) (protonated bis-aminal) pK(a) = (7.6 +/- 0.2). the pK(a) of the protonated bis-aminal could only be determined at the higher ionic strength. The results are in good agreement with reported values determined using the classic formol titration. The automated titration system acquired the full time course of the pH change upon each titrant addition allowing a kinetic analysis to be performed as well as an equilibrium analysis. The forward and reverse rate constants for M + L left arrow over right arrow ML were 0.77M(-1) sec(-1) and 8.1 x 10(-4) sec(-1). respectively.     

Modeling Pb(II) adsorption onto sandy loam soil

The adsorption of Pb(II) onto hydrous sandy loam soil was investigated with batch equilibrium adsorption experiments. Results show that the amount of Pb(II) adsorbed increases with increasing pH and surface loading. It was demonstrated that the surface acidity of the soil could be determined using electrophoretic mobility measurements. The surface acidity constants, pK(a1)(int) and pK(a2)(int), were 1.57 and 3.43, respectively. A surface complex formation model (SCFM) was employed to describe the adsorption. The intrinsic stability constants, pK(i)(s), for the surface reaction between the Pb species and the ionized soil surface hydroxyl groups were determined from SCFM fitting. The adsorption free energy of Pb2+ and Pb(OH)+ ions ranges from -5.74 to -6.48 kcal/mol and from -9.68 to -10.00 kcal/mol, respectively, for surface loadings between 1.21 x 10(-5) and 2.41 x 10(-4) mol/g. The adsorption binding calculation indicated that the specific chemical interaction is the major mechanism responsible for the adsorption process.     

稀土与多卤代变色酸双偶氮胂类试剂的配合反应研究

本文研究了稀土与卤代变色酸双偶氮胂类试剂的配合反应,测定了配合物的稳定常数,试剂的离解常数和配合物组成,讨论了试剂结构与配合物吸收光谱的关系和β型配合物的生成条件,从而探讨了该类试剂在高酸度下与稀土的配合反应机理.     

Phototautomerism in the lowest excited singlet state of 1-hydroxy-2-carboxyanthraquinone

The dependence of the absorption and fluorescence spectra of 1-hydroxy-2-carboxy-anthraquinone on pH and Hammett acidity have been studied. This compound exhibits phototautomerism in its uncharged and its singly-charged anionic species in aqueous media. Its ground state (pK(a)) and lowest excited singlet-state (pK(a)( *)) dissociation constants have been determined by absorptiometric and fluorimetric titrations and the assignment of the pK(a) and pK( *)(a) values to the equilibria concerned has been carefully considered.     

Multiparametric curve fitting-IX Simultaneous regression estimation of stoichiometry and stability constants of complexes

A chemical model (i.e., the number of complexes, their stoichiometry and stability constants with molar absorptivities) in solution equilibria may be established by (i) the trial-and-error method in which stability constants are estimated for an assumed set of complexes in the mixture and a fitness test is used to resolve a choice of plausible models to find the true one; (ii) the simultaneous estimation of the stoichiometry and stability constants for species divided into "certain" species for which the parameters beta(pqr), (p, q, r) are known and held constant, and "uncertain" species with unknown parameters which are determined by regression analysis. The interdependence of stability constants and particular sets of stoichiometric indices requires that the computational strategy should be chosen carefully for each particular case. The benefits and limitations of both approaches are compared by means of examples of potentiometric titration data analysis by the POLET(84) program and of spectrophotometric data analysis by the SQUAD(84) program. A strategy for efficient computation is suggested.     

Acidity and alkali metal adsorption on the SiO2-aqueous solution interface

The intrinsic deprotonation constant (pK(a(2))(int)) and the intrinsic ion exchange constants (pK(Me(+))(int)) of Li(+), Na(+), and K(+) on SiO(2) were uniquely determined at 30 degrees C by using the potentiometric titration data, the Gouy-Chapman-Stern-Grahame (GSCG) model for the structure of the electrical double-layer (edl) and the double-extrapolation method. The values of these constants were pK(a(2))(int) = 6.57, pK(Li(+))(int) = pK(Na(+))(int) = pK(K(+))(int) = 5.61. The chemical meaning of intrinsic equilibrium constants and the equality in the values of pK(Li(+))(int), pK(Na(+))(int) and pK(K(+))(int) were discussed.     

Equilibrium studies of the diorganotin(IV) complexes with some amino acids and related compounds

The interaction of dimethyltin(IV) and diethyltin(IV) cations with water and some amino acids and related compounds was investigated at 25 degrees C and ionic strength 0.1 M NaNO(3) using a potentiometric technique. The results showed the formation of 11 and 12 (organotin:ligand) complexes and the corresponding stability constants were determined. The participation of different ligand functional groups in binding to organotin is discussed. The effect of the pK(a) value of the respective ligand on the stability constant of its complex species was elucidated. The concentration distribution of the complexes in solution was evaluated.     

Computer calculation of equilibrium concentrations in mixtures of metal ions and complexing species

A method is described for calculating equilibrium concentrations of all species in multi-metal-multi-ligand mixtures from the pH of the solution, the total concentration of each metal and each complexing agent, and the relevant equilibrium constants (pK(a) values and stability constants). No restriction is imposed on types of possible complexes, which can include mixed, hydrolysed, protonated and polynuclear species. Two examples are given. One of these comprises a 10-metal-10-ligand system (195 equilibrium constants). In the second system, mixed complex formation is important. The computer program is given.     

5-Methyl-2-[3-(4-phenylthiazol-2-yl)triazenyl]benzenesulfonic acid as a chromogenic reagent of N-cetylpyridinium chloride Synthesis, mechanism and analytical application

Despite that triazene reagents have been widely used for spectrophotometric determinations of cationic surfactants, the mechanism underlying such applications has yet to be studied. We report the synthesis of a new triazene reagent 5-methyl-2-[3-(4-phenylthiazol-2-yl)triazenyl]benzenesulfonic acid (MPTTBSA) and its interaction with N-cetylpyridinium chloride (CPC). The reagent was synthesized by coupling 4-methyl-2-sulfobenzenediazonium salt with 2-amino-4-phenylthiazole. Spectral evidence suggests that the neutral reagent (H(2)R) exists in a triazenium sulfonate zwitterion form. Two ionizations were detected at weak acidic (H(2)R/HR(-), pK(a1) 2.71+/-0.20) and alkaline pH (HR(-)/R(2-), pK(a2) ca. 13.5), respectively. In the presence of 3.5 equivalents of CPC, a 2.71 unit decrease in pK(a1) and a 3.0 unit decrease in pK(a2) were observed. While the optical properties of H(2)R are essentially unaffected, CPC causes a 53nm red shift and a 31nm red shift in maximum absorption wavelengths (lambda(max)), and a 24% increase and a 29% increase in extinction coefficients (epsilon) of HR(-) and R(2-), respectively. These data suggest that CPC forms ion associates with HR(-) and R(2-), but its interaction with H(2)R is weak. Associations of CPC with HR(-) and R(2-) both follow a 3:1 stoichiometry, and the apparent stability constants of the two associates were estimated as 6.02x10(18) and 2.42x10(22)M(-3), respectively. Consistent with their high stability constants, the two ion associates did not show any changes in optical properties under submicellar and micellar conditions. The strict 3:1 association stoichiometry was interpreted in terms of electrostatic-induced, topology-defined pi-stacking and hydrophobic interactions, which not only change the optical properties of the reagent anions, but also provide the driving force to shift the two ionization equilibria to the right and cause the decreases in pK(a). Compared to the first ionization, perturbation of the second ionization by CPC provides a color reaction that is more sensitive and has a better color contrast, which was used to develop a new protocol for spectrophotometric determination of CPC. This is the first mechanistic study on the interaction between a triazene reagent and a cationic surfactant.     

Potentiometric determination of equilibrium constants of bases and perchlorates of protonated bases in glacial acetic acid using Superquad

The traditional method of calculating equilibrium constants in glacial acetic acid medium was developed by Kolthoff and Bruckenstein in 1957; thenceforth, and even presently, few alternatives have been made available to undertake such studies. This paper presents the results obtained with the use of the program Superquad to assess the equilibrium constants of various bases and their protonated perchlorate salts in glacial acetic media. A model of formation equilibria is proposed and fed into the program, considering the species present during an acid-base titration. The calculations of the equilibrium constants using Superquad for pyridine and diethylamine are statistically in agreement with those reported in the literature, (for pyridine: pK(B)=5.98+/-0.02, pK( PyHClO4)=5.47+/-0.02 and for diethylamine pK(B)=5.52+/-0.04, pK( DietHClO4)=4.52+/-0.07). With the use of Superquad, the values found for the aniline were pK(B)=6.95+/-0.06 and pK( AnilHClO4)=4.89+/-0.06.     

In Process Citation

The proton concentration resulting from the dissociation of a moderately strong dibasic acid can be precisely determined by means of an acid-base indicator by differential spectrophotometry. The dissociation constants are then calculated by linear regression of the appropriate function. The method was tested on the first two dissociation constants of protonated O-phosphoserine in aqueous solution (25 degrees , KNO(3) 0.1M): the values found are pK(1) = 0.72 (3sigma = 0.08) and pK(2) = 2.14(6) (3sigma = 0.01).     

Analysis of the kinetic stability of yttrium chelates by free-ion selective radiotracer extraction (FISRE)

Within this work the analysis of the kinetic stability of a series of yttrium complexes, i.e., Y-citrate, Y-NTA, Y-CDTA as well as Y-humic acid (Y-HA) has been successfully performed by the free-ion selective radiotracer extraction (FISRE) method. FISRE uses ⁹⁰Y with a high specific activity to perform CHELEX extractions in a buffered aqueous solution at pH 6 in two different modes by monitoring the dissociation and association reactions of the corresponding complexes. Whereas in the case of Y-citrate the dissociation profile could be successfully described in terms of (pseudo) first order kinetics, the other complexes tend to form two species with different kinetic properties, although only one species is predicted by speciation calculations. In the batch FISRE method, all (except Y-NTA) corresponding association rate constants were determined by monitoring the formation rate of the yttrium complexes.     

A fast high throughput method for the determination of acidity constants by capillary electrophoresis. 3. Basic internal standards

A set of 25 monoprotic bases is proposed as internal standards for pK(a) determination by capillary electrophoresis. The pK(a) of the bases is determined and compared with available literature data. The capillary electrophoresis internal standard method offers numerous advantages over other typical methods for pK(a) determination, especially of analysis time and buffer preparation. However, it requires disposing of appropriate standards with reference pK(a) value. The set of bases established in this work together with the set of acids previously established provide a reference set of compounds with well-determined acidity constants that facilitate the process of selecting appropriate internal standards for fast pK(a) determination by capillary electrophoresis in high throughput screening of pharmaceutical drugs. In addition, the performance of the method when acidic internal standards are used for the determination of acidity constants of basic internal standards has also been tested. Although higher errors may be expected in this case, good agreement is observed between determined and literature values. These results indicate that in most cases structural similarity between the analyte and the internal standard might not be an essential requirement in the internal standard method.     

A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: effects of fluorine substitution on pKa and binding affinity and evidence for intermolecular C-F...CN interactions

The H-atoms of the phenylamidinium needle of tricyclic thrombin inhibitors, which interacts with Asp189 at the bottom of the selectivity pocket S1 of the enzyme, were systematically exchanged with F-atoms in an attempt to improve the pharmacokinetic properties by lowering the pK(a) value. Both the pK(a) values and the inhibitory constants K(i) against thrombin and trypsin were decreased upon F-substitution. Interestingly, linear free energy relationships (LFERs) revealed that binding affinity against thrombin is much more affected by a decrease in pK(a) than the affinity against trypsin. Surprising effects of F-substitutions in the phenylamidinium needle on the pK(a) value of the tertiary amine centre in the tricyclic scaffold of the inhibitors were observed and subsequently rationalised by X-ray crystallographic analysis and ab initio calculations. Evidence for highly directional intermolecular C-F...CN interactions was obtained by analysis of small-molecule X-ray crystal structures and investigations in the Cambridge Structural Database (CSD).     

Determination of the intrinsic site pK(a) value and cooperativity of the symmetrical hexadentate chelator N,N',N'-tris[2-(3-hydroxy-2-oxo-1,2-dihydropyridin-1-yl)acetamido]ethylamine

The three overlapping pK(a) values of N,N',N'-tris[2-(3-hydroxy-2-oxo-1,2-dihydropyridin-1-yl)acetamido]ethylamine, a tripodal hexadentate chelator formed from three 3-hydroxy-2(1H)-pyridinone moieties amide linked to tris-(2-aminoethyl)amine, were determined by simultaneous spectrophotometric and potentiometric titration. The data was analysed by non-linear regression with constraints to deal with (a) the highly correlated absorptivities and (b) the highly correlated pK(a) values. The three pK(a) values were optimized first from the spectrophotometric data (absorbance vs. pH) by non-linear regression to a model in which the molar absorptivity of the ith species ((i)) was constrained by the correlation equation (i) = epsilon (0) + (epsilon (3) - epsilon (0))i 3 with i = 0, 1, 2, 3, where (3) and (0) represent the molar absorptivities of the most protonated and least protonated species, respectively. The molar absorbitivity of the four species defined by three pK(a) values is, therefore, linearly related to proton stoichiometry. The pK(a) values were then optimized from the potentiometric data (pH vs. titrant volume) by non-linear regression to a model in which the three pK(a) values were constrained by the correlation equation pK(a(i)) = pK(a(int)) + b(i - 1) + (i - 2)log(3) where i = 1, 2 or 3. This expresses the three pK(a) values in terms of only two optimizable parameters, the intrinsic site pK(a) (pK(a(int))) and the interaction energy between sites (b). The fixed term (i - 2)log(3) accounts for the statistical effect on the pK(a) values of three equivalent ionizable sites. The modified analytical derivatives required for optimization of these parameters by the Gauss-Newton-Marquardt algorithm and the merits of optimizing pK(a) values with these two correlation equations are discussed. The optimized pK(a) values were 9.31 +/- 0.01, 8.75 +/- 0.01 and 8.19 +/- 0.01. The separation between pK(a) values is 0.58 comprising 0.477 for the statistical effect and 0.081 for the interaction energy while the intrinsic site pK(a) is 8.672 +/- 0.005. The tertiary amine at the centre of the tripodal backbone has a pK(a) of 5.88 +/- 0.03.     

Stability constants of the ternary complexes of CuDTPA, NiDCTA, CrEDTA, CoHEEDTA, NiHEEDTA and CuHEEEDT Aheedta with OH-

The acid dissociation constants of the metal chelates H(3)CuDTPA, H(2) NiDCTA, HCrEDTA, HCoHEEDTA, HNiHEEDTA and HCuHEEDTA were determined by potentiometric titration. The constants determined at an ionic strength of 0.1 were pK(a,1) = 2.1; pK(a,2) = 2.8 and pK(a,3) = 4.75 for H(3) CuDTPA (296 K), pK(a,1) = 2.16 for HCrEDTA (298 K); pK(a,1) = 1.6 and pK(a,2) = 2.0 for H(2) NiDCTA (298 K); pK(a,1) = 2.24 for HCoHEEDTA, pK(a,1) = 2.47 for HCuHEEDTA and pK(a,1) = 1.73 for HNi-HEEDTA. At high pH the formation of ternary hydroxo-complexes was observed for the chelates CrEDTA(-) (pK(a,1) = 7.35; pK(a,1) = 12.35), CoHEEDTA(-) (pK(a,1) = 11.74), NiHEEDTA(-) (pK(a,2) = 12,44) and CuHEEDTA(-) (pK(a,2) = 10.45).