This study explores the self-assembly of water-lean solvents into tetrameric clusters, enabling novel CO₂ capture chemistry. Single-component water-lean solvents, such as N-(2-ethoxyethyl)-3-morpholinopropan-1-amine (EEMPA), self-assemble into tetrameric clusters that facilitate CO₂ capture through the formation of carbamate anhydrides and carbamic acid. These clusters exhibit hydrogen-bonded internal cores, similar to enzymatic active sites, which enable the formation of CO₂-containing molecular species. The study combines experimental and modeling approaches to elucidate the mechanism of CO₂ capture, revealing a two-stage process involving cooperative binding and thermodynamic features. The self-assembly of these clusters enhances CO₂ capture efficiency and enables the formation of carbamate anhydrides, which can act as initiators for future oligomerization or polymerization of CO₂. The research highlights the potential of water-lean solvents for CO₂ capture, offering a pathway to materials with higher CO₂ storage capacity and novel chemical functionalities. The findings suggest that the unique properties of these tetrameric clusters could lead to more efficient and sustainable CO₂ capture technologies, with implications for carbon capture, utilization, and storage. The study also provides insights into the thermodynamics and kinetics of CO₂ capture, demonstrating the potential for designing new materials with tailored properties for CO₂ capture and conversion.This study explores the self-assembly of water-lean solvents into tetrameric clusters, enabling novel CO₂ capture chemistry. Single-component water-lean solvents, such as N-(2-ethoxyethyl)-3-morpholinopropan-1-amine (EEMPA), self-assemble into tetrameric clusters that facilitate CO₂ capture through the formation of carbamate anhydrides and carbamic acid. These clusters exhibit hydrogen-bonded internal cores, similar to enzymatic active sites, which enable the formation of CO₂-containing molecular species. The study combines experimental and modeling approaches to elucidate the mechanism of CO₂ capture, revealing a two-stage process involving cooperative binding and thermodynamic features. The self-assembly of these clusters enhances CO₂ capture efficiency and enables the formation of carbamate anhydrides, which can act as initiators for future oligomerization or polymerization of CO₂. The research highlights the potential of water-lean solvents for CO₂ capture, offering a pathway to materials with higher CO₂ storage capacity and novel chemical functionalities. The findings suggest that the unique properties of these tetrameric clusters could lead to more efficient and sustainable CO₂ capture technologies, with implications for carbon capture, utilization, and storage. The study also provides insights into the thermodynamics and kinetics of CO₂ capture, demonstrating the potential for designing new materials with tailored properties for CO₂ capture and conversion.