Lech Chmurzyński

A potentiometric study of acid-base equilibria of substituted pyridines in acetonitrile

Abstract Acid dissociation, as well as cationic homo- and heteroconjugation equilibria have been studied by potentiometric titration for pyridine and a variety of its mono- and di-substituted derivatives in the polar protophobic aprotic solvent, acetonitrile. The heteroconjugation equilibria were investigated in several BH + /B 1 systems without proton transfer in which the p K a values of the protonated form of the proton acceptor were lower than those of the proton donor. The p K a values of acids conjugated with the heterocyclic N-bases determined in acetonitrile fall within the p K a range of 4.5–18.5 and are on an average 8–9 orders of magnitude higher than corresponding p K a s of these species in water. The ranking order of the p K a values of the protonated amines is the same in both solvents, thus providing the basis for establishing linear correlations of these values. Moreover, the results of potentiometric measurements have also shown that cationic homoconjugation equilibria are present in the BH + /B systems studied. The homoconjugation constants are relatively small falling in the log K BHB + range between 1 and 2. Further, the acidity and cationic homoconjugation constant values in acetonitrile were compared with those determined in another polar protophobic aprotic solvent, propylene carbonate. It has been concluded that acetonitrile better differentiates between the strengths of cationic acids and is more favourable for attaining cationic homoconjugation equilibria than propylene carbonate. Furthermore, it has been found that cationic heteroconjugation equilibria are not attained in the majority of the amine systems studied. The heteroconjugation constant could be determined in one system studied only and was of the order of two on the logarithmic scale.

Ionic equilibria of pyridine N-oxide perchlorates in acetonitrile

Abstract Ionic association constants of pyridine N-oxide perchlorate and semiperchlorate have been determined conductometrically as well as limiting molar conductances of PyOH+ and PyOHOPy+ cations in acetonitrile. The acid dissociation constant of the protonated pyridine N-oxide and the cationic homoconjugation constant of pyridine N-oxide with conjugated cationic acid have been found from potentiometric measurements. On the bass of determined values of the equilibrium constants, a scheme of fundamental ionic equilibria in the acetonitrile solutions of the perchlorates has been suggested.

Acid-base equilibria in systems involving substituted pyridines in polar aprotic protophobic media and in the amphiprotic methanol

Abstract Acid dissociation, as well as cationic homo- and heteroconjugation constants have been determined by potentiometric titration in systems involving substituted pyridines and conjugate cationic acids in the polar protophobic aprotic solvent acetone and in polar amphiprotic methanol. The values of the constant were compared with those previously determined in other polar protophobic aprotic solvents, acetonitrile, nitromethane and propylene carbonate. The p K a values of the protonated pyridine derivatives in acetone range between 2.69 and 12.69 and are on average 2–3 orders of magnitude higher than those determined in water. The p K a values in methanol vary between 1.02 and 10.37, and are only slightly higher than those in water, the difference not exceeding one order of magnitude. A comparison of the acid dissociation constants determined in all the non-aqueous solvents considered shows that the strength of the cationic acids increases on going from acetonitrile through nitromethane, propylene carbonate and acetone to methanol. In almost all systems of the type: a pyridine derivative its conjugate acid, the cationic homoconjugation equilibrium is present in acetone (1.60 K BHB + K BHB + N -bases and the conjugate cationic acids increases in the solvents studied as follows: propylene carbonate K BHB 1 + =2.13). In methanol, the tendency towards heteroconjugation in the systems studied is markedly greater. As a matter of fact, the heteroconjugation constants are lower (1.58 K BHB 1 +

Acid-base equilibria of substituted pyridine N-oxides in methanol

Acid dissociation constants in methanol for eight substituted pyridine N-oxides having a wide range of acid-base properties, [quinoline N-oxide (bi-cyclic amine N-oxide) and pyridine (heterocyclic amine)] have been determined using the potentiometric titration method. A linear correlation between ourmethanol data and aqueous pKa values from the literature has been found. As in polar aprotic solvents cationic homoconjugation phenomenon has been found to be present for sufficiently basic N-oxides. The tendency of substituted pyridine N-oxides towards cationic homoconjugation in methanol is weaker than in polar aprotic solvents and increases with increasing basicity of N-oxides. It has also been found that, in contrast to polar aprotic solvents, the cationic homoconjugation phenomenon in methanol is much more pronounced for heterocyclic amines than their N-oxides.

Acid–base and hydrogen-bonding equilibria in aliphatic amine and carboxylic acid systems in non-aqueous solutions

Abstract Acid–base and hydrogen-bonding equilibria in acetic acid – acetate, n-butylammonium cation – n-butylamine and acetic acid (acetate) – n-butylamine (n-butylammonium cation) systems were studied in five polar non-aqueous solvents with varying prototropic and dielectric properties: acetonitrile, acetone, dimethyl sulfoxide, methanol, and propylene carbonate using the potentiometric-titration technique. These systems were designed to model the acid–base and hydrogen-bonding phenomena that involve acid and basic amino-acid side chains in proteins. The obtained order of p K a values of acetic acid and n-butylamine is consistent with the variation of prototropic, basic, dielectric, and hydrogen-bonding properties of the solvents used. The homoconjugation and heteroconjugation constant values decrease with increasing basicity of the solvents; they turn out to be indeterminable in dimethyl sulfoxide (the most basic solvent) for cationic homoconjugation and in methanol (the second most basic solvent) for anionic homoconjugation and heteroconjugation.

Studies on correlations of acid-base properties of substituted pyridine N-oxides in solutions. Part 1. Correlations of the pKa values in non-aqueous solvents and water

Abstract The strength of cationic acids conjugated with substituted pyridine N -oxides has been compared in a number of polar non-aqueous media including aprotic (protophilic and protophobic), as well as amphiprotic solvents. The solvents studied have been arranged in the following sequence of increasing acid strength of the protonated N -oxides: acetonitrile N , N -dimethylformamide K a values of the cationic acids in these solvents has been found to be the same as in water. Based on this observation linear relationships between the aqueous and non-aqueoues p K a values were established. Values of correlation coefficients r provided a criterion for the classification of the media into two classes. The first class involved those solvents in which a high accuracy of determination of the acid-base equilibrium constants could be achieved, while the other one encompassed the media which limited significantly the precision of results. Interpretation of the slope a and intercept b in these correlations has been given as well. Application of the parameters a and b as a criterion for differentiation of aprotic solvents (as protophilic and protophobic ones) has been suggested. Some examples for using the correlation of this type to the indirect determination of aqueous p K a values based on the non-aqueous ones have been presented. It has been concluded that the good correlations between the p K a values in aqueous and non-aqueous solutions enables the estimation of chosen value (aqueous or non-aqueous) with satisfactory accuracy even in cases when the experimental limitations make their precise determination impossible.

Zinc(II) complexation by some biologically relevant pH buffers.

The isothermal titration calorimetry (ITC) technique supported by potentiometric titration data was used to study the interaction of zinc ions with pH buffer substances, namely 2‐(N‐morpholino)ethanesulfonic acid (Mes), piperazine‐N,N′‐bis(2‐ethanesulfonic acid) (Pipes), and dimethylarsenic acid (Caco). The displacement ITC titration method with nitrilotriacetic acid as a strong, competitive ligand was applied to determine conditional–independent thermodynamic parameters for the binding of Zn(II) to Mes, Pipes, and Caco. Furthermore, the relationship between the proposed coordination mode of the buffers and the binding enthalpy has been discussed. Copyright

Analysis of Fluorescence Quenching of Coumarin Derivatives by 4-Hydroxy-TEMPO in Aqueous Solution

The fluorescence quenching of different coumarin derivatives (7-hydroxy-4-methylcoumarin, 5,7-dimethoxycoumarin, 7-amino-4-methyl-3-coumarinylacetic acid, 7-ethoxy-4-methylcoumarin, 7-methoxycoumarin, 7-hydroxycoumarin, 7-hydroxy-4-methyl-3-coumarinylacetic acid and 7-amino-4-methylcoumarin) by 4-hydroxy-TEMPO in aqueous solutions at the room temperature was studied with the use of UV–Vis absorption spectroscopy as well as a steady-state and time-resolved fluorescence spectroscopy. In order to understand the mechanism of quenching the absorption and fluorescence emission spectra of all coumarins along with fluorescence decays were recorded under the action of 4-hydroxy-TEMPO. The Stern-Volmer plots (both from time-averaged and time-resolved measurements) displayed no positive (upward) deviation from a linearity. The fluorescence quenching mechanism was found to be entirely dynamic, what was additionally confirmed by the registration of Stern-Volmer plots at different temperatures. The Stern-Volmer quenching constants and bimolecular quenching rate constants were obtained for all coumarins studied at the room temperature. The findings demonstrate the possibility of developing an analytical method for the quantitative determination of the free radicals’ scavenger, 4-hydroxy-TEMPO.

Influence of charge and size of terminal amino‐acid residues on local conformational states and shape of alanine‐based peptides

We present results of conformational studies by Circular dichroism and NMR spectroscopy, differential scanning calorimetry, and molecular dynamics, of three alanine‐based peptides: Ac‐KK‐(A)7‐KK‐NH2 (KAK), Ac‐OO‐(A)7‐DD‐NH2 (OAD), and Ac‐KK‐(A)7‐EE‐NH2 (KAE), where A, K, O, D, and E, denote alanine, lysine, ornithine, aspartic acid, and glutamic acid residues, respectively. For OAD and KAE, canonical MD simulations with time‐averaged NMR‐derived restraints demonstrate the presence of an ensemble of structures with a variety of conformational states (polyproline II, α‐helical, α′, and extended, turn); for KAK the conformational states are predominantly polyproline II and extended. The OAD peptide exhibits a bent shape with its ends close to each other, whereas KAK and KAE are more extended. The bent shape was also observed in our earlier study of the Ac‐XX‐(A)7‐OO‐NH2 (XAO) peptide, where X denotes the diaminobutyric acid residue; therefore, the shape seems to depend on the size of the charged side chains at the ends of the alanine sequence and not on their kind. This suggests that the bent shape of the alanine sequence is formed to enable screening of this nonpolar sequence from the solvent by sufficiently short charged side chains. As in our previous study of the XAO peptide, no long polyproline II segments were observed.

Acidic‐basic properties of three alanine‐based peptides containing acidic and basic side chains: Comparison between theory and experiment

The purpose of this work was to evaluate the effect of the nature of the ionizable end groups, and the solvent, on their acid‐base properties in alanine‐based peptides. Hence, the acid‐base properties of three alanine‐based peptides: Ac‐KK‐(A)7‐KK‐NH2 (KAK), Ac‐OO‐(A)7‐DD‐NH2 (OAD), Ac‐KK‐(A)7‐EE‐NH2 (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid, lysine, and ornithine, respectively, were determined in water and in methanol by potentiometry. With the availability of these data, the ability of two theoretical methods to simulate pH‐metric titration of those peptides was assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3 force field and the Poisson‐Boltzmann approach to compute solvation energy (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field and the Generalized Born model (MD/GB/pH). For OAD and KAE, pKa1 and pKa2 correspond to the acidic side chains. For all three compounds in both solvents, the pKa1 value is remarkably lower than the pKa of a compound modeling the respective isolated side chain, which can be explained by the influence of the electrostatic field from positively charged ornithine or lysine side chains. The experimental titration curves are reproduced well by the MD/GB/pH approach, the agreement being better if restraints derived from NMR measurements are incorporated in the conformational search. Poorer agreement is achieved by the EDMC/PB/pH method.