Anion-cation contrast of small molecule solvation in salt solutions.

Stefan Hervø-Hansen,Jan Heyda,Nobuyuki Matubayasi,Mikael Lund

doi:10.1039/d1cp04129k

Abstract

The contributions from anions and cations from salt are inseparable in their perturbation of molecular systems by experimental and computational methods, rendering it difficult to dissect the effects exerted by the anions and cations individually. Here we investigate the solvation of a small molecule, caffeine, and its perturbation by monovalent salts from various parts of the Hofmeister series. Using molecular dynamics and the energy-representation theory of solvation, we estimate the solvation free energy of caffeine and decompose it into the contributions from anions, cations, and water. We also decompose the contributions arising from the solute–solvent and solute-ions interactions and that from excluded volume, enabling us to pin-point the mechanism of salt. Anions and cations revealed high contrast in their perturbation of caffeine solvation, with the cations salting-in caffeine via binding to the polar ketone groups, while the anions were found to be salting-out via perturbations of water. In agreement with previous findings, the perturbation by salt is mostly anion dependent, with the magnitude of the excluded-volume effect found to be the governing mechanism. The free-energy decomposition as conducted in the present work can be useful to understand ion-specific effects and the associated Hofmeister series.

Highlights

Due to the previously mentioned reasons, and due to caffeine possessing a chemical structure related to the purine nucleobases of DNA and RNA, the physical properties of caffeine has been exhaustively investigated by a great variety of methodologies, including experimental, computational, and theoretical methods
E-mail: nobuyuki@cheng.es.osaka-u.ac.jp; Fax: +81-6-6850-6343; Tel: +81-6-6850-6565 † Electronic supplementary information (ESI) available: An electronic Jupyter notebook can be found at https://zenodo.org/record/5836851 allowing the results presented to be reproduced
The ratio of the solubilities at equilibrium is related to the difference in the solvation free energy upon addition of co-solvent DDGsol[48]

Summary

Introduction

Due to the previously mentioned reasons, and due to caffeine possessing a chemical structure related to the purine nucleobases of DNA and RNA, the physical properties of caffeine has been exhaustively investigated by a great variety of methodologies, including experimental, computational, and theoretical methods. In neutron scattering experiments, caffeine has been found to possess a selfassociation equilibrium, forming highly ordered oligomers characterised by the face-to-face stacking of the xanthine motif,[7,8,9,10] similar to the stacking of the nucleobases found in DNA and RNA.[11] the formation of larger aggregates has been reported, in which the oligomers are branched at the methyl groups.[12] The mentioned equilibria; the partitioning of caffeine in the aqueous and organic phases, and the self-association of caffeine are all subject to modulation by osmolytes such as sugars,[13,14,15] and salts..

Methods

Results

Conclusion