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)


 

 
 
 

Webinar “Mobile Phase pH in Liquid Chromatography” on April 29, 2021

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.

Mobile phase pH is the topic of an upcoming webinar “Mobile Phase pH in Liquid Chromatography”, which we will organise on 29.04.2021 at 13:00 – 16:00 (Central European time: France, Germany, …) via the Zoom platform. Registration to the webinar is now open at this registration link.

The topics that we plan to cover are:

— 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

The webinar is organised in the framework of the project 17FUN09 “UnipHied”, 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.

 

 

 

 

 

Acidity scale in acetonitrile: 231 pKa values spanning 30 orders of magnitude

The equilibrium acidity scale (pKa scale) in acetonitrile (MeCN) has been supplemented by numerous new compounds and new ΔpKa measurements and has been published in Eur. J. Org. Chem. 2021, 1407–1419 (Open access). The pKa scale now contains altogether 231 acids – over twice more than published previously – linked by 566 ΔpKa measurements and spans between the pKa values of hydrogen iodide (2.8) and indole (32.57), covering close to 30 orders of magnitude. The acids have wide structural variety, ranging from common families – phenols (e.g. picric acid, alizarin, polyhalogenophenols), carboxylic acids (e.g. acetic, benzoic, retinoic and sorbic acid), sulfonic acids, hydrogen halides) to highly special molecules (chiral BINOL catalysts, bis(benzoxazole-2-yl)methanes, polyfluorinated compounds) and superacids (fluorinated sulfonimides, cyanoform, tetracyanopropenes).

Measurement results acquired over the last 15 years were added to the scale and new least squares treatment was carried out. The treatment yielded revised pKa values for the compounds published previously, with the root mean square difference between revised and previous values 0.04, demonstrating very good stability of the scale.

Correlation equations were developed for estimating pKa values for the studied types of compounds in water, DMSO, DMF and 1,2-dichloroethane on the basis of pKa values in acetonitrile. These equations enable predicting pKa values with an average error around or less than 1 pKa unit, which is a sufficient accuracy for many applications.

The scale is expected to be a useful tool for the widest possible research areas in organic chemistry, electrochemical power sources, catalysis, etc.

Symmetric Potentiometric Cells for the Measurement of Unified pH Values

Recently the UnipHied consortium published a new article – Symmetric Potentiometric Cells for the Measurement of Unified pH Values. Symmetry 2020, 12, 1150, where we compared the performance of different cells and instruments used to measure acidities on the unified pH scale (pHabs). The advantage of the unified pH scale is that it enables expressing the acidities of any systems – non-aqueous, solutions, colloidal systems, etc – via pHabsH2O values, which are directly comparable to the conventional pH values of the aqueous pH scale.

This is the first time unified acidities have been measured outside of our group. Nine partners from Europe – national metrology institutes and universities – have set up systems to measure pHabs and validated them with standard aqueous buffers.

The results show that the method is robust and does not depend on the cell nor the instrument (pH meter, potentiostat, or electrometer). The inherent symmetry of the cell design helps to reduce the experimental workload and improve the accuracy of the obtained results.

The next step is to measure unified acidities of non-aqueous systems, which could be used by routine laboratories to calibrate their pH electrodes.

The UnipHied project is funded from the EMPIR programme (project 17FUN09) co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme.

Our collection of acidity and basicity data in non-aqueous media has been updated!

The collections of experimental acidity and basicity data in non-aqueous media measured by our group are now up to date on our Chair of Analytical Chemistry webpage. 

Both tables include the compounds name, CAS number and SMILES code. The acidity collection contains 190 compounds, where the compounds available experimentally measured pKa in acetonitrile (MeCN) and pKip in 1,2-dichloroethane (DCE) are given. The pKa in DCE is calculated/estimated based on pKip value. 

The basicity data collection includes 353 compounds and their pKip in tetrahydrofuran (THF) and in DCE. The pKa values in MeCN were re-evaluated taking into account all (close to 700) measurements of 279 bases. Therefore, these pKa values can be considered the most reliable pKa values measured in MeCN available!

Our acid-base research at 19th European Symposium on Fluorine Chemistry 2019

On 26.08.19 at 19th European Symposium on Fluorine Chemistry 2019 Ivo Leito gave a talk Acidities of molecules and media: the united pKa-pHabs scale in 1,2-dichloroethane.

For the first time in a low-polarity solvent, the scale has a dual nature, being both a pKa scale of the involved acids (i.e. describing acidity of molecules) and at the same time a pH scale, describing the acidity of the solutions (media).

The scale spans 28 orders of magnitude (pH or pKa units) and is composed of 87 acids of diverse nature. The scale is linked to the unified acidity (pHabs) scale and expressed in values, which makes the acidities of the solutions directly comparable to the conventional aqueous pH scale. This in turn makes the scale a useful tool in future studies of acid-driven processes (reaction mechanisms, catalysis, strong oxidants, etc) in low-polarity media.

This work has been published in: Chem. Sci., 2017, 8, 6964-6973. A unified view to Brønsted acidity scales: do we need solvated protons?.

It is part of a larger endeavor – to promote a wider usage the unified pH scale by the research and technology communities, which is currently in progress via the UnipHied. The project is funded from the EMPIR programme (project 17FUN09) co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme.