# Rotational Spectroscopy Pinpoints the Tetrahydrate as the Onset of Water Self-Aggregation in Sevoflurane Hydration

## TL;DR

This study uses rotational spectroscopy to show how water molecules start to self-aggregate when forming clusters with the anesthetic sevoflurane.

## Contribution

The study identifies the tetrahydrate as the first stage where water-water interactions dominate over sevoflurane-water interactions.

## Key findings

- Up to four water molecules were added to sevoflurane and characterized using rotational spectroscopy.
- Two isomers of the tetrahydrate were detected, showing a cyclic structure similar to pure water tetramers.
- The tetrahydrate marks a transition where water-water interactions drive the formation of the water network.

## Abstract

Characterizing
the interactions between water and volatile
anesthetics
at a molecular level is crucial for understanding their mechanisms
of action. We employed broadband molecular rotational spectroscopy
(CP-FTMW) and extensive isotopic substitution experiments to generate
and characterize the stepwise addition of up to four water molecules
to the volatile anesthetic sevoflurane, a flexible molecule with multiple
binding sites. The substantial amount of isotopic data enabled the
conclusive derivation of accurate structural information. The observed
structures contain the most stable conformer of the previously identified
monomer, with water clusters favorably interacting with the molecule
to form an open chain with up to three water molecules. Notably, two
isomers were detected for the tetrahydrate, which exhibit a cyclic
structure with either a clockwise or anticlockwise orientation, resembling
that of the pure water tetramer. The four-water marks a transition
where water–water interactions dominate over direct sevoflurane–water
interactions driving the assembly of the water network.