Switching Site Selectivity in Alkoxyamine Hydration: From Lone-Pair Direction to Solvent Network Dominance
Filippo Baroncelli1, Luca Evangelisti1,2, Juan Carlos López3
1Department of Chemistry G. Ciamician, University of Bologna, I-40129 Bologna, Italy.
Journal of the American Chemical Society
|July 7, 2026
Summary
Predicting solvation in complex molecules is hard. This study shows N,N-diethylacetyloxyamine (DEAcA) hydration shifts from nitrogen to oxygen as water clusters grow, revealing a transition in molecular recognition.
Area of Science:
- Chemical Physics
- Molecular Spectroscopy
- Computational Chemistry
Background:
- Predicting solvation site selectivity in multifunctional organic molecules is challenging.
- Understanding early-stage solvation is crucial for molecular recognition and reaction mechanisms.
- N,N-diethylacetyloxyamine (DEAcA) presents competing nitrogen and oxygen acceptor sites.
Purpose of the Study:
- To investigate the hydration landscape of N,N-diethylacetyloxyamine (DEAcA).
- To determine the site selectivity of water molecule binding at different hydration levels.
- To elucidate the transition from localized molecular interactions to collective solvent network stabilization.
Main Methods:
- High-resolution rotational spectroscopy to probe molecular structure and interactions.
- Quantum-chemical calculations to model hydration structures and energies.
- Analysis of 14N nuclear quadrupole coupling (NQC) constants to confirm nitrogen site interactions.
Main Results:
- The isolated DEAcA monomer favors a syn configuration.
- Microsolvation (n=1-3 water molecules) shows exclusive preference for the nitrogen acceptor site.
- At n=4 water molecules, a structural transition occurs, with solvation shifting to the carbonyl oxygen via a cyclic water tetramer.
- 14N NQC constants provide experimental evidence for cooperative polarization in water chains.
Conclusions:
- Solvation behavior of DEAcA transitions from nitrogen-centered interactions to collective stabilization by a cyclic water tetramer at the carbonyl oxygen.
- The study highlights a critical point where localized stereoelectronic control yields to bulk-like solvent network effects.
- The findings offer a benchmark for computational models predicting solvation in complex organic systems.
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