At the recent Balticum Organicum Syntheticum conference Ivo Leito made a presentation titled How to make maximum use of the available pKa data in non-aqueous solvents? (Photo on the left)

The presentation started with how acid and base strengths, typically expressed as pK_a values (acids) or pK_aH values (bases), depend on solvation of the proton, as well as of the neutral and ionized forms of the acid/base. Every solvent has different solvation properties. Thus, the pK_a values for the same acid/base in different solvents are also different (often dramatically different).

In principle, whenever using pK_a values for predicting or rationalizing chemical processes, the pK_a values determined in the same solvent should be used. In some solvents, e.g. water, DMSO or acetonitrile large bodies of pK_a data exist, while in most solvents either very few pK_a values are available or none at all. This leads to the frequent need of estimating pK_a values in one solvent from the data in other solvent(s) (Picture on the right). An additional consideration is the (often problematic) quality of pK_a data in the literature.

When estimating pK_a values in one solvent based on the data in another solvent it is important to clearly define the aim. Is it needed to have the absolute pK_a value or is it rather necessary to have the acidity/basicity differences (or acidity/basicity order) within a set of compounds? Perhaps the question is just “can base B deprotonate acid A in solvent S”? If absolute pK_a value is needed then what accuracy is necessary? Depending on the aim, there are different possibilities of estimating pK_a and pK_aH values in a solvent on the basis of data in other solvents.

The presentation gave an overview to what extent such estimates can be usefully done, highlighting both successes and failures, as well as how to recognize clearly erroneous pK_a data. The presentation also highlighted the IUPAC project Critical compilation of acid pKa values in polar aprotic solvents that is nearing completion. The critically evaluated pK_a data of acids in dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, pyridine, acetone, propylene carbonate, tetrahydrofuran are available from Ivo Leito on request.

The presentation turned out to be highly interesting for the participants, receiving a large amount of questions, which extended well into the coffee break!

(This research was supported by grant PRG690 from the Estonian Research Council)

On 7th of August, 2024, Kerli Martin successfully defended her PhD dissertation titled Recognition of carboxylates by synthetic receptors – from structure-affinity studies to solid-contact anion-selective electrode prototyping.

This dissertation begins with the observation that while polymer membrane ion-selective electrodes (ISEs) have been well known and widely used for decades to detect small cations, determining organic anions with ISEs remains a challenge, essentially without a solution. The dissertation presents a journey starting with the study of the interactions between small monocarboxylates and numerous anion receptors – potential new ionophores.

By measuring the binding constants of eight carboxylates (formate, acetate, pivalate, lactate, ibuprofen, ketoprofen, glucuronate, and benzoate) to 44 synthetic receptor molecules using nuclear magnetic resonance, Kerli constructed eight binding affinity scales where all the binding affinities are comparable. These results were then assembled into a large overall map of the receptor-anion binding constants (Figure on the right). The results revealed that the selected synthetic hydrogen-bond donor receptors can distinguish between carboxylates with different structures.

As a result of this binding study, a 1,3-bis(carbazolyl)urea derivative (receptor 13 in the Figure on the right) was selected as the hydrogen-bonding ionophore to create prototypes of ion-selective electrodes that can detect acetate. The electrodes built by Kerli displayed a unique selectivity pattern for different anions. The addition of this ionophore to the electrode membrane significantly (by up to several orders of magnitude) reduced the interference from other common ions such as chloride, bromide and nitrate. Kerli’s work is an important step forward in designing ionophores that can specifically bind carboxylates and building sensitive and selective ion-selective electrodes for different anions.

The defence procedure itself was quite a battle for Kerli! It started with the detailed questioning by the opponent prof. Claudia Caltagirone (University of Cagliari, Italy) on all the aspects of the thesis. Particularly interesting and difficult were some of her highly technical questions regarding the fluorescence measurement of binding affinities. Then there was a long string of questions from the defence committee members. The topics of Kerli’s thesis ranged from receptor-anion binding to computational chemistry and from materials science to hard-core electrochemistry. Thus, most committee members found something familiar and worth asking about. Kerli managed nicely with all the questions and left a very good impression on everybody in the room!

Please accept our warm congratulations, Kerli!

During recent years, we have been engaged in extensive investigations of the unified pH (pH_abs) values of reversed-phase liquid chromatography (RPLC) mobile phases. The pH_abs scale has the advantage over the conventional pH scale because pH_abs values express acidity in terms of the thermodynamic activity of the solvated proton. Therefore, pH_abs values are directly comparable between solvents/media of different compositions. At the same time, pH_abs is convenient to use, as pH_abs values of aqueous solutions are equal to the respective conventional pH values.

This comparability is especially useful in RPLC, as mobile phases are mixtures of water with organic solvents in different ratios. Thus, it can be said that pH_abs is the best way of expressing pH if a rigorous comparison of pH between solutions in different solvents is needed.

As a result of our work, we have carefully measured the pH_abs values of 78 mobile phases commonly used in RPLC, using around 300 individual ΔpH_abs measurements between different mobile phases (see the “ladder” scheme below). This is, to the best of our knowledge, the most comprehensive collection of rigorous pH_abs values of RPLC mobile phases and has now been published as A. Heering, M. Lahe, M. Vilbaste, J. Saame, J. P. Samin, I. Leito. Improved pH measurement of mobile phases in reversed-phase liquid chromatography. Analyst 2024.

The ΔpH_abs values were measured by differential potentiometry, using potential differences in a symmetric cell with two glass electrode half-cells (see figure above) and almost ideal ionic liquid triethylamylammonium bis((trifluoromethyl)sulfonyl)imide [N₂₂₂₅][NTf₂] salt bridge with multiple overlapping measurements. The system of altogether 300 ΔpH values, pictured in the “ladder” scheme below, was anchored to the pH value of standard pH 7.00 aqueous buffer solution.

In addition, a simpler measurement method that uses double junction reference or double junction combined electrodes was tested and was found suitable for routine laboratories. The results show that the design of the junction is an important factor in deciding if the electrode can be used for unified acidity measurements. This is the first successful use of double junction combined electrodes filled with ionic liquid for the measurement of pH_abs values.

The article is featured in the themed collection Analyst HOT Articles 2024.

(This research was supported by grant PRG690 from the Estonian Research Council)