EMPIR programme project
17FUN09 “UnipHied





The acidity/basicity of liquid media strongly impacts chemical, biological, environmental and industrial processes. pH is the most widely used acidity measure of solutions/media. However, accurate evaluation of pH is currently possible only in a very limited range of media and pH values in different media are not comparable.

This project will revolutionize pH measurement via putting a novel pH definition into practice, leading to a better understanding and control of a variety of processes crucial in many real-world situations. An experimental absolute/unified pH scale valid in any medium (pHabs scale) and respective measurement methods will be developed that allow rigorous comparison of acidity between any liquid media. pHabs will be applied to 3 separate problems to demonstrate its capabilities: (1) accurate quantification of pH in highly acidic media, (2) evaluation of pH of solvent mixtures used in liquid chromatography, (3) rationalization of acid catalysis in low-polarity solvents.


Unified pH Scale – from Concept to Applications

On April 16, 2024, prof. Ivo Leito presented the topic of “Unified pH Scale – from Concept to Applications” at the 8th Baltic Electrochemistry Conference: Finding New Inspiration 2 (BEChem 2024), held in Tartu, Estonia. 

At the beginning of the presentation, Ivo gave a brief overview of why pH, a widely used value for expressing acidity, has serious limitations. Thus, it cannot be used to compare the acidities of solutions in different solvents, which can hinder the understanding of chemical, biological, environmental, and industrial processes.

A much more practical approach could be the usage of an absolute/universal pH, which would allow the comparison of acidities in different solvents. Thus, the main part of the presentation was focused on the theoretical and practical aspects of unified pH (pHabs). In recent years, our Acid-base Studies workgroup in the Analytical Chemistry Chair has worked extensively with the development and measurement of unified pH values for various systems in different solvents (liquid chromatography modile phases, electrocatalytic mixtures, strongly acidic solutions, etc). A differential potentiometry method for pHabs has been developed in the workgroup to obtain the unified pH values and has been now distributed to a number of groups in Europe in the framework of the UnipHied project.

For now, the unified pH has matured from a concept into a practical tool and has been accepted both by the European metrology community (Euramet) and by IUPAC. The unified pH could be utilized in various applications, such as liquid chromatography, catalytic systems, and acidity at the interfaces between phases. 

The presented research is largely the result of the EMPIR programme project 17FUN09 “UnipHied”.

Dr. Andre Leesment – PhD thesis on the acidity in biphasic systems and gas-phase

Last Friday, June 9th, 2023, Andre Leesment successfully defended his PhD thesis titled Quantitative studies of Brønsted acidity in biphasic systems and gas-phase. The opponent was Prof. Kiyohiko Sugano from the Ritsumeikan University, Japan.

Dr. Andre Leesment (on the right) after his PhD defence with his supervisor Prof. Ivo Leito (on the left).

Experiments for measuring acidity of medicines, catalysts, and other chemicals are almost always performed under monophasic conditions. However, many of them are lipophilic compounds, and in biphasic systems they prefer the nonpolar organic phase, where their properties are much different from their properties in an aqueous phase. Yet the interactions with the organic phase are completely ignored in a typical acidity measurement. It’s like seeing only half of the picture. Why is such an incomplete approach being used for something this important?

Until recently, there was no theoretical basis or experimental method to conduct measurements of acidity under more relevant conditions. Andre’s PhD thesis focuses on providing the tools to measure acidity, and by extension, many other properties of molecules in biphasic systems in a more realistic and accurate way. Hopefully, these tools lead to a more effective drug development, catalyst research, etc.

Congratulations to you, Andre!  


Unified pH – what, why and how?

On March 10, 2023, Ivo Leito presented “Unified pH – what, why and how?” at the Chemistry and Chemical Technology 2023 Vilnius (Lithuania).

Acidity is one of the most critical characteristics of solutions. Its measurement is crucial to understanding and controlling essential processes in fundamental chemistry, industry and living organisms, such as catalysis, extraction, chromatography, processes in micelles/bilayers, etc.

Acidity refers to the activity of the solvated proton and is typically expressed as pH. However, the conventional pH scale is well established only in dilute aqueous solutions at medium pH values. It has severe limitations at extreme values, in other solvents or more complex media where most real-life chemistry occurs. Most importantly, comparing the conventional pH values between different media is impossible because every solvent has its pH scale.

Given the above, a decade ago, the concept of a “unified pH scale” was put forward, defining unified pH via the absolute chemical potential of the solvated proton. The merits of this approach are a strict thermodynamic foundation and direct comparability of values between any media.

In recent years, to a large part thanks to the European Union UnipHied (17FUN09) project, the measurement possibilities have been developed and the concept has now been published as an IUPAC technical report.

The first part of the presentation gave theoretical background and explained the need for unified pH. The second part described the experimental method, and the last part gave an overview of the work done and future perspectives.


Quantifying acidity in heterogeneous systems: Biphasic pKa values

As a result of a recent development in our group, it is now, for the first time, possible to rigorously measure acidity of acids in biphasic systems (aqueous phase at equilibrium with a water-immiscible phase) by using biphasic pKa values (pKaow values). This work has now been published in Analytical Chemistry 2022, 94, 4059–4064.

In this work, the octanol-water biphasic pKaow values have been determined for 35 acids of various structures and chemical properties (carboxylic acids, phenols, diphenylamines, imides, different CH acids) using UV-Vis and NMR (1H, 13C, or 31P) spectrometry.

Biphasic pKa values enable quantifying acid dissociation in biphasic systems in a more realistic and rigorous way than the conventional “mono-phasic” pKa values. The latter completely ignores a large part of the picture – partitioning of the neutrals and the ions between the two phases and ion-pairing in the low-polarity phase. In contrast, pKaow values account for these effects. The ratio of the acid and its conjugate base is measured in the 1-octanol phase, using UV-Vis and/or NMR spectrometric method. The activity of H+ is measured in the aqueous phase with a conventional pH-meter. The pKaow values are obtained at different concentrations and extrapolated to zero concentration.

Biphasic systems are present in many biological and technological systems and processes: cell membranes, solvent extraction, phase-transfer catalysis, sensor membranes, etc. In all such systems, acid-base properties of the participating compounds would be best described using biphasic rather than “mono-phasic” pKa values.

Webinar “Mobile Phase pH in Liquid Chromatography”

On Apr 29, 2021 the webinar “Mobile Phase pH in Liquid Chromatography” took place. Altogether 101 people participated from 41 countries, ranging from Portugal to Philippines and from Peru to Nepal.

It is well known that in liquid chromatography, mobile phase pH is an important parameter, significantly affecting the retention of acidic and basic analytes. Yet, mobile phase pH is tricky to measure because mobile phases are usually aqueous-organic mixtures and in the case of gradient elution mobile phase composition gradually changes during elution. The topics covered during the webinar were:

— Different possibilities to express pH in liquid chromatography (LC)
Unified pH (pHabs): the concept and measurements methods
— The applications and limitations of different pH expressions in LC

Numerous questions were asked by the participants that indicated the importance of the topic and the need for a more robust conceptual framework for handling the topic of pH in liquid chromatography. Contributing to this, via the pHabs concept, is one of the aims of the UnipHied project.

The webinar was organized in the framework of the PRG690 project from the Estonian Research Council and the  UnipHied project (www.uniphied.eu), which  is funded from the EU’s EMPIR programme, co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme. Additional support from: EU Regional Development Fund (TK141 “Advanced materials and high-technology devices for energy recuperation systems”) and Estonian Center of Analytical Chemistry (www.akki.ee)