Stepwise Hydration Reveals Conformational Switching in Chiral Prolinol.

Area of Science:

• Physical Chemistry
• Chemical Physics
• Molecular Interactions

Background:

• Water's role in chemical and biological processes necessitates understanding chiral molecule interactions.
• Prolinol is a key chiral auxiliary in asymmetric synthesis, making its hydration behavior significant.

Purpose of the Study:

• Investigate the interactions between the chiral amino alcohol prolinol and 1-3 water molecules.
• Determine how water influences prolinol's conformation and hydrogen bonding in different hydration states.

Main Methods:

• Broadband rotational spectroscopy was used to study prolinol-(H2O)n complexes (n=1-3).
• Nuclear Magnetic Resonance (NMR) studies and molecular dynamics simulations were employed for bulk water analysis.

Main Results:

• Bare prolinol exists in low-energy conformations with an O-H---N hydrogen bond.
• One water molecule forms addition and insertion structures without altering prolinol's conformation.
• Two or three water molecules induce prolinol to adopt high-energy conformations (N-H---O hydrogen bond), acting as a conformational switch.
• In bulk water, prolinol exists as a flexible ensemble, lacking stable intramolecular hydrogen bonds and sampling conformations similar to the di- and tri-hydrated states.

Conclusions:

• Stepwise hydration profoundly changes the conformational landscape of flexible chiral molecules like prolinol.
• Water's ability to act as a conformational switch is demonstrated, with implications for solvation-induced processes.
• Findings provide a basis for future research on solvation effects in chiral chemistry and biology.