The Spanish Biophysical Society highlights a study by the EHU’s spectroscopy group

Physical Chemistry applies the principles and concepts of physics to understand the basics of chemistry and explain how and why transformations of matter take place on a molecular level. One of the branches of this field focusses on understanding how molecules change in the course of a chemical reaction or process.

Understanding the interactions of chiral molecules with water is crucial, given the central role that water plays in chemical and biological processes. Chiral molecules are those that, despite comprising the same atoms, cannot be superimposed on their mirror image in a way similar to what happens with right and left hands or a pair of shoes.

In this context, the Spectroscopy Group of the University of the Basque Country / Euskal Herriko Unibertsitatea (EHU) and the Biofisika Institute (CSIC/EHU), led by Emilio J. Cocinero, investigated the interactions of prolinol (a chiral catalyst and auxiliary widely used in asymmetric synthesis) with one, two and three water molecules. The study is part of the group's line of research focusing on the structural analysis of relevant molecules using high-resolution spectroscopic techniques, and has recently been highlighted by the Spanish Biophysical Society (SBE).

“This work has made it possible to connect three scales that are normally studied separately: the isolated molecule, microsolvation with a few water molecules, and behaviour in solution,” explained Emilio J. Cocinero, a researcher at the EHU and the Biofisika Institute (CSIC/EHU).

The results show directly that water does not act exclusively as a passive 'medium’, but that it fulfils an active role in the conformation adopted by the molecules. “We observed that just a few water molecules are capable of changing the preferred structure of a chiral molecule completely. This is important because the conformation of a molecule determines how it recognises others, how it reacts or how it functions in a biological or chemical environment,” pointed out Cocinero.

Prolinol is a small, but highly representative molecule. It is widely used as a catalyst and as a building block in chemical synthesis; moreover, it has two key functional groups (an alcohol and an amine) that interact strongly with water. This makes it an ideal model for studying how water competes with the internal bonds of the molecule and can force structural changes. What is more, its flexible structure allows the effects induced by hydration to be clearly observed. “By adding water step by step, we can see that prolinol adopts conformations that under normal conditions would be ‘unfavourable’. The water acts as a true conformational switch,” added the researcher.

The study is also underpinned by an experimental approach that combines ultra-high-resolution rotational spectroscopy with theoretical calculations and studies in solution by means of NMR and simulations. This combination makes it possible to connect in great detail what happens when only a few water molecules interact with prolinol with the actual behaviour of the molecule in solution. “To understand how molecules behave in water, it is sometimes enough to look closely at what just two or three solvent molecules do. We believe that this idea is relevant to many other chemical and biological systems,” he concluded.

Additional information

The study was carried out in collaboration with the Chemistry Department of King’s College London, the Chemistry Department of the University of Virginia, the Institute of General Organic Chemistry (IQOG-CSIC) in Madrid, the Chemistry Department and the Chemistry Research Institute of the University of La Rioja.

END