Märt Lõkov works in our group focusing on investigations of acid-base equilibria – first of all, determination of acidity and basicity constants (pK_a values) of molecules – in nonaqueous solutions. This is a core research direction in our group and he is one of the key people in advancing it.

He has made significant contributions to the self-consistent acidity scale and self-consistent basicity scale in acetonitrile, containing pK_a values 231 acids and pK_aH values of 279 bases, respectively. Because of how these values have measured (“multiple overlapping” relative spectrophotometric measurements), these scales are widely regarded as the most reliable sets of pK_a values in acetonitrile. Thus, assembling those scales was to a large extent also a revision of existing pK_a values for many compounds and assigning new values to them.

Märt has mastered the art of pK_a measurements in nonaqueous media to the highest degree and is right now one of the most skilful people on planet Earth in performing nonaqueous pK_a measurements. Besides doing these measurements himself, he has supervised and is supervising numerous master’s and doctoral students who measure pK_a values in their degree projects. Thus, indirectly, via the supervised students, his contribution is even larger.

Perhaps the most ambitious endeavour that Märt is now engaged in is a large-scale re-evaluation and revision of pK_a values of carboxylic acids in three nonaqueous solvents – acetonitrile, DMSO, dimethylformamide. The analysis of available pK_a data that we have carried out in the framework of the IUPAC project 2015-020-2-500 Critical compilation of acid pK_a values in polar aprotic solvents reveals that the non-aqueous pK_a values available in the literature for this very important compound class are often significantly in error, sometimes by several orders of magnitude. The revision will involve measurements and analysis of literature data. Märt has assembled a group of people involving several students and the expected outcome will be a large amount of high-quality nonaqueous pK_a data of carboxylic acids.

These contributions have been noticed by the International Union of Pure and Applied Chemistry (IUPAC) and Märt has been awarded the Balarew Award for an Outstanding Young Scientist working in the field of critical evaluation of solubility and/or related chemical equilibria!

Märt, please accept our warm congratulations!

(A part of this research was supported by grant PRG690 from the Estonian Research Council)

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!