Acid Dissociation Constant pKa Research Articles

Streaming Potentials of Hyaluronic Acid Hydrogel Films.

The streaming potentials of hyaluronic acid (HA) hydrogel films are measured and theoretically interpreted by systematically varying the HA concentration and the streaming electrolyte pH and ionic strength. While Donnan potentials are expected to vanish with sufficient added salt, apparent ζ-potentials from the Helmholtz-Smoluchowski interpretation remain of the order -20 mV. To theoretically interpret these data, we derived an electrokinetic model (valid in the Debye-Hückel regime) that accounts for ionic and hydrodynamic permeability of the gels. The films could then be ascribed an effective acid dissociation constant pKa ≈ 4.2, specific HA charge ≈-0.1e mmol g-1, and Brinkman/hydrodynamic permeability ∼ S1/3, where is the Brinkman length for HA solutions in the as-prepared reference state and S is the hydrogel swelling ratio. At an ionic strength of 10 mmol L-1, for example, the HA surface potentials are only ψD/2 ≈ -8 mV, where ψD is the Donnan potential, considerably lower than ζ-potentials furnished by the Helmholtz-Smoluchowski interpretation. This insight significantly changes how the films are expected to interact with other surfaces and colloids via Derjaguin-Landau-Vervey-Overbeek-type forces. Our analysis furnishes formulas for the swelling ratio S and hydrodynamic permeability , expressed explicitly as simple power-law functions of the as-prepared HA concentration cha (wt %), consistent with independent assessments of the HA solution permeability and polyelectrolyte-hydrogel swelling theory. These may prove valuable for extrapolating the results to other combinations of ionic strength, pH, and HA and cross-linking concentrations.

Direct assessment of the acidity of individual surface hydroxyls.

The state of deprotonation/protonation of surfaces has far-ranging implications in chemistry, from acid-base catalysis1 and the electrocatalytic and photocatalytic splitting of water2, to the behaviour of minerals3 and biochemistry4. An entity's acidity is described by its proton affinity and its acid dissociation constant pKa (the negative logarithm of the equilibrium constant of the proton transfer reaction in solution). The acidity of individual sites is difficult to assess for solids, compared with molecules. For mineral surfaces, the acidity is estimated by semi-empirical concepts, such as bond-order valence sums5, and increasingly modelled with first-principles molecular dynamics simulations6,7. At present, such predictions cannot be tested-experimental measures, such as the point of zero charge8, integrate over the whole surface or, in some cases, individual crystal facets9. Here we assess the acidity of individual hydroxyl groups on In2O3(111)-a model oxide with four different types of surface oxygen atom. We probe the strength of their hydrogen bonds with the tip of a non-contact atomic force microscope and find quantitative agreement with density functional theory calculations. By relating the results to known proton affinities of gas-phase molecules, we determine the proton affinity of the different surface sites of In2O3 with atomic precision. Measurements on hydroxylated titanium dioxide and zirconium oxide extend our method to other oxides.

Open-source QSAR models for pKa prediction using multiple machine learning approaches

BackgroundThe logarithmic acid dissociation constant pKa reflects the ionization of a chemical, which affects lipophilicity, solubility, protein binding, and ability to pass through the plasma membrane. Thus, pKa affects chemical absorption, distribution, metabolism, excretion, and toxicity properties. Multiple proprietary software packages exist for the prediction of pKa, but to the best of our knowledge no free and open-source programs exist for this purpose. Using a freely available data set and three machine learning approaches, we developed open-source models for pKa prediction.MethodsThe experimental strongest acidic and strongest basic pKa values in water for 7912 chemicals were obtained from DataWarrior, a freely available software package. Chemical structures were curated and standardized for quantitative structure–activity relationship (QSAR) modeling using KNIME, and a subset comprising 79% of the initial set was used for modeling. To evaluate different approaches to modeling, several datasets were constructed based on different processing of chemical structures with acidic and/or basic pKas. Continuous molecular descriptors, binary fingerprints, and fragment counts were generated using PaDEL, and pKa prediction models were created using three machine learning methods, (1) support vector machines (SVM) combined with k-nearest neighbors (kNN), (2) extreme gradient boosting (XGB) and (3) deep neural networks (DNN).ResultsThe three methods delivered comparable performances on the training and test sets with a root-mean-squared error (RMSE) around 1.5 and a coefficient of determination (R2) around 0.80. Two commercial pKa predictors from ACD/Labs and ChemAxon were used to benchmark the three best models developed in this work, and performance of our models compared favorably to the commercial products.ConclusionsThis work provides multiple QSAR models to predict the strongest acidic and strongest basic pKas of chemicals, built using publicly available data, and provided as free and open-source software on GitHub.

Elusive pKa’ of aminoferrocene determined with voltammetric methods in buffered and unbuffered systems and practical aspects of such experiments

Redox behaviour of aminoferrocene (FcNH2) in buffered and unbuffered systems has been studied. In unbuffered solutions with background electrolyte only, two discrete redox pairs of unprotonated and protonated forms were evident. On the other hand, in buffered systems only one redox centre was visible continuously shifting with pH.If one wants to determine the apparent acid dissociation constant pKa’ of ferrocene with protonatable side group, buffered environment will be the first choice. Throughout the electrochemical experiments at such conditions, the most limiting factor was the type of the electrode – gold, platinum, glassy carbon and boron-doped diamond electrodes were probed. We found that the influence of the surface of the electrode was so significant that either the determination of pKa’ was not possible at aqueous conditions or observed differences among the determined values were up to five units. In that case, elusive constants were determined. On the other hand, titrations performed in unbuffered systems appeared to be useable despite inconsistences and deficiencies that can be expected. Determined pKa's agreed well with that quantified using spectrophotometry. Although, experimental work at unbuffered conditions can be considered as incorrect or misleading at the first sight, interesting facts and unexpected mechanisms can be revealed. Especially, when one is aware of the possible risks, and the measurement in different (even unbuffered) media and with different tools are done simultaneously. Finally, a method for estimation of pKa’ of unstable compounds without their separation and isolation was introduced.

ФИЗИКО-ХИМИЧЕСКИЕ СВОЙСТВА N-(2,2-ДИМЕТИЛПРОПАНОИЛ)-N'-П-ТОЛУОЛСУЛЬФОНИЛГИДРАЗИНА

The physico-chemical properties (solubility, propensity to foaming, surface activity, acid-base properties, acid dissociation constant pKa) of N-(2,2-dimethylpropanoyl)--N'-p-toluenesulfonylhydrazine were studied.Acid dissociation constant values: pKa1=8,31±0,05 andpKa2=13,34±0,10. The reagent does not show surface activity in alkaline solutions.

Prediction of acid dissociation constants of organic compounds using group contribution methods

In this paper, group contribution (GC) property models for the estimation of acid dissociation constants (Ka) of organic compounds are presented. Three GC models are developed to predict the negative logarithm of the acid dissociation constant pKa: (a) a linear GC model for amino acids using 180 data-points with average absolute error of 0.23; (b) a non-linear GC model for organic compounds using 1622 data-points with average absolute error of 1.18; (c) an artificial neural network (ANN) based GC model for the organic compounds with average absolute error of 0.17. For each of the developed model, uncertainty estimates for the predicted pKa values are also provided. The model details, regressed parameters and application examples are highlighted.

Equilibrium partitioning of naphthenic acids and bases and their consequences on interfacial properties

This article aims to create a model to accurately predict the equilibrium partitioning of naphthenic acids and basic crude oil components between the oil and water phase. The model was tested on 2 acids and 2 bases. After a review of the properties of crude oil acids and bases, the equilibrium partitioning of acids and bases with different molecular weight was analyzed over a pH interval using heptane as the oil phase and 3.5wt.% NaCl as the water phase. Phenylacetic acid would represent the low molecular weight acid while 4-heptylbenzoic acid was chosen to represent the high molecular weight one. Likewise, 4-ethylaniline and 4-decylaniline were chosen as corresponding bases. The partitioning of the two acids and the low molecular weight base was successfully modelled by considering the acid dissociation constant pKa in aqueous phase and the partition ratio Pwo of the non-ionized species between oil and aqueous phase. The high molecular weight base did not significantly partition into the aqueous phase at the pH range studied. The results show that acid species are more water soluble than basic species of similar molecular weight. In presence of calcium the partitioning of acids is successfully modelled by accounting for the precipitation of naphthenate soap with a solubility constant Ks. The kinetic interfacial tension between heptane and 3.5% NaCl aqueous buffer was also analyzed with oils that contained single compounds, two bases, two acids and all four components over a pH interval to identify any interfacial acid-base interactions. No significant interfacial interaction could be identified, mostly due to similar pKa values.

Formation Constants of Copper(II) Complexes with Tripeptides Containing Glu, Gly, and His: Potentiometric Measurements and Modeling by Generalized Multiplicative Analysis of Variance

We report a systematic study of the effects of types and positions of amino acid residues of tripeptides on the formation constants logβ, acid dissociation constants pKa, and the copper coordination modes of the copper(II) complexes with 27 tripeptides formed from the amino acids glutamic acid, glycine, and histidine. logβ values were calculated from pH titrations with l mmol L(-1):1 mmol L(-1) solutions of the metal and ligand and previously reported ligand pKa values. Generalized multiplicative analysis of variance (GEMANOVA) was used to model the logβ values of the saturated, most protonated, monoprotonated, logβ(CuL) - logβ(HL), and pKa of the amide group. The resulting model of the saturated copper species has a two-term model describing an interaction between the central and the C-terminal residues plus a smaller, main effect of the N-terminal residue. The model supports the conclusion that two copper coordination modes exist depending on the absence or presence of His at the central position, giving species in which copper is coordinated via two or three fused chelate rings, respectively. The GEMANOVA model for pKamide, which is the same as that for the saturated complex, showed that Gly-Gly-His has the lowest pKamide values among the 27 tripeptides. Visible spectroscopy indicated the formation of metal-ligand dimers for tripeptides His-His-Gly and His-His-Glu, but not for His-His-His, and the formation of multiple ligand bis compexes CuL2 and Cu(HL)2 for tripeptides (Glu/Gly)-His-(Glu/Gly) and His-(Glu/Gly)-(Glu/Gly), respectively.

Synthesis, Tautomeric Structure, Dyeing Characteristics, and Antimicrobial Activity of Novel 4-(2-Arylazophenyl)-3-(2-hydroxyphenyl)-1-phenyl-2-pyrazolin-5-ones

Novel azopyrazolin-5-one dyes 4a-f were synthesized by the regioselective reaction of phenylhydrazine with 2,3,4-chromantrione-3-arylhydrazones 2a-f. The acid dissociation constants pKa for the series prepared were determined and correlated by the Hammett equation. The results of such correlation together with the spectral data indicated that the studied compounds exist predominantly in the hydrazone keto structure, (D) as the Z-configuration. The dyes were applied to polyester fabrics, affording orange-yellow shades and assessments of their dyeing performance are considered. Further, the compounds 4a-f were screened for their antimicrobial activity against various microorganisms.

Fluorescence Analysis of Acridine Orange Adsorbate at the Water/ N -Heptane Interface, Bulk and Interface

The amphiphilic nature of 3, 6-bisdimethylaminoacridine (trivial name, acridine orange) can be used to characterize (polar/nonpolar) interfaces. This paper studies the properties of acridine orange and its dodecyl derivative at a solvent interface by internal reflection and tension determinations. In the case of absorbance measurements of crystallized acridine orange, the potenz value of the conventional acid dissociation constant pK a was found to be 9.6. A clear isosbestic point could be obtained after purification at a unique pH for different concentrations. In contrast, in the absorbance measurements of acridine orange dodecyl, no isosbestic point was observed; this was attributed to the free long dodecyl chain. The overlap in the absorbance spectrum and the normalized fluorescence spectrum was found in many solvents around 500 nm. Neutral species were more likely to transfer into organic phase upon shaking. For fluorescence measurements both steady-state and time-resolved spectra were investigated. Results showed that at the interface a bathochromic shift happened to the maxima. This means that chromophore species aggregated at the interface as the dimer or trimer or the macro oligomer. Fluorescence polarization in bulk was calculated and found to be ca. 0.4. For interfacial measurements a dynamic volume method was applied to obtain the interfacial tension. An extrapolated Gibbs plot was obtained. Increasing bulk concentration increased the concentration at the interface to a finite value representing saturation.

UV and MO study on the deprotonation of some 2‐aryl‐Δ2‐1,3,4‐oxadiazoline‐5‐thiones

AbstractSubstituent effects on the deprotonation processes of a series of 2‐aryl‐Δ2‐1,3,4‐oxadiazoline‐5‐thione (1) derivatives have been studied experimentally as well as theoretically. The acid dissociation constants pKa have been determined spectrophotometrically in ethanol‐water solutions (7.5‐92.5%) and vary between 3.76 and 5.80. Semiempirical molecular orbital (MO) calculations (AM1 and PM3) were used for the investigation of the existence of possible tautomeric thione and thiol forms of the studied compounds. Strong correlation between the pKa values and the deprotonation enthalpies were evaluated.

Redox reactivity of the type 1 (blue) copper protein amicyanin from Thiobacillus versutus with inorganic complexes

Electron-transfer reactions of the type 1 copper protein amicyanin from Thiobacillus versutus with [Co(terpy)2]2+(terpy = 2, 2′:6′, 2″-terpyridine) as a reductant for AmCuII, and [Fe(CN)6]3– and [Co(phen)3]3+(phen = 1, 10-phenanthroline) as oxidants for AmCuI have been explored by stopped-flow kinetic studies at 25 °C, I= 0.100 M (NaCl). The reaction with [Co(terpy)2]2+ is a straightforward single-stage process, whereas both the oxidaltions give biphasic kinetics. The first stages of the latter exhibit an active-site ‘switch-off’ mechanism previously assigned as a protonation (and dissociation) of the His-96 ligand of AmCuI. From the studies with [Co(phen)3]3+ an acid dissociation constant pKa of 6.6 and rate constant at the higher pH of 7.1 × 103 M –1 s–1 are obtained. The reaction with [Fe(CN)6]3–gives similar behaviour with a pKa, of 6.6, and from the fitting procedure adopted, a rate constant at the higher pH of 8.3 × 1 06 M–1s–1, which is at the upper limit of the stopped-flow range. The second stage of the reaction is explained by the formation of a less-reactive form of AmCuI in amounts of between 5 and 40% depending on the pH. The rate law in the case of [Co(phen)3]3+ is independent of oxidant concentration, shows little dependence on pH and gives rate constants (a) in the range 0.07–0.12 s–1. For the more reactive [Fe(CN)6]3– the rate equation is k2obs=a+b[Fe(CN)63–], with a varying between 0.1 3 and 0.1 5 s–1 and b= 680 M–1s–1. The similar values of a for the two reactions are consistent with a common rate-controlling intramolecular isomerisation step. The bimolecular rate constant b is ≈ 104 times smaller than the rate constant for the first stage of the [Fe(CN)6]3– oxidaltion at pH ≈ 8. The nature of the structural differences between the two forms of AmCuI is considered.

Kinetic studies on 1 : 1 electron-transfer reactions involving blue copper proteins. Part 12. Reactions of spinach plastocyanin with inorganic redox partners

Reactions of spinach plastocyanin have been studied at 25 °C, I= 0.10 M (NaCl), and a comparison is made with the previously studied parsley plastocyanin, which has 31 different residues in a single polypeptide chain of 99 amino-acid residues. Active-site protonations leading to a switch-off in reactivity of PCu (I) are notably different, as indicated by the acid dissociation constants pKa for spinach (4.9 average) and parsley (5.5). Protonation of PCu(II) at the east-face binding site, which incorporates Tyr 83, gives similar pKa′ values of 5.6 (spinach) and 5.8 (parsley). A number of other features are similar, including rate constants at pH 7.5 with [Fe(CN)6]3–, [Co(phen)3]3+(phen = 1, 10-phenanthroline), and [Co(dipic)2]–(dipic = dipicolinate) as oxidants for PCu(I), and [Ru(NH3)5(py)]2+(py = pyridine) and [Co(terpy)2]2+(terpy = 2, 2′:6′2″-terpyridyl) as reductants for PCu(II), which are all within ±33% of those for parsley plastocyanin, suggesting conservation of binding sites, reduction potential, and mechanism of electron transfer. With [Fe(CN)6]3– as oxidant, reaction is assigned to the His 87 (north) site, whereas with [Co(phen)3]3+ reaction occurs at two (or more) binding sites with (from the effect of H+)ca. 70% of reaction at the Tyr 83 site. The oxidant [Ru(NH3)5(CH3CN)]3+ has been used for the first time. Blocking with redox inactive [(NH3)5Co(NH2)Co(NH3)5]5+(KB= 6 300 M1, pH 7.5) suggests that 91 % of this reaction is at the Tyr 83 site. From similar blocking experiments with [Co(phen)3]3+ as oxidant the corresponding value is 80%(61% for parsley). Only mild association and blocking is observed with Mg2+(K≈ 38 M–1).

The influence of the structure of chelating agents on the complexity and distribution constants of thorium complexes

AbstractThis paper deals with results obtained by the distribution method described in the preceding paperMargareta Dyrssen, The application of solvent extraction to the study of chelate complexes of thorium, p. 748. . This work still being in progress and new data may considerably change the present picture. For those interested in the chemistry of coordination compounds the value of the acid dissociation constants pka and the mean complexity constants a of ThA4 are of the greatest interest. For those interested in metal extraction log K is very importantDefinitions of the complexity constants ka, a, and K: cf. M. Dyrssen, p. 750, eqs (8), (2), (11) respectively. .It has been generally recognised that when comparing the reaction of a series of chelate ligand ions A− with hydrogen ion and with a metal ion MN+ the respective equilibrium constants ka and k1 show the same trend; i.e. there appears to be a correlation between acid strength and chelate stabilityH. Rossotti, this volume page 763. . Furthermore it has been observed that 5‐membered chelate rings are more stable than 6‐ or 4‐membered ones. Such generalisations are however not sufficient to explain the behaviour of so different chelating agents as e.g. oxine, cupferron and acetylacetone. Some properties which at the present time seem relevant to the stability of the chelate‐complexes of H+ and Th4+ will be discussed here.