Wrapping an Ester with CO ₂ ─Until Water Breaks In

Esters are key components in CO₂-based solvents and reactions, yet their microscopic interactions with CO₂ remain poorly defined. Using high-resolution rotational spectroscopy combined with quantum-chemical analysis, we directly observed how CO₂ binds and organizes around methyl formate, the simplest ester. Three dimer isomers were detected, revealing competing carbonyl- and ether-based binding motifs with population ratios of 87:10:3. As more CO₂ molecules attach, they form a cage-like network that progressively encapsulates the carbonyl site. Remarkably, a single water molecule can replace CO₂, forming cooperative H₂O<b>···</b>CO₂ interactions and redirecting the aggregation pathway. By bridging binary and ternary clusters, this work establishes the first direct insights for ester-CO₂ recognition and demonstrates how the delicate balance between dispersion-biased encapsulation and hydrogen bonding competition by water dictates molecular organization, offering a molecular-level framework for understanding solvation, selectivity, and reactivity in CO₂-rich environments.