Neutral-to-zwitterionic transition in protonated glycine clusters drives magic number stability

Molecular clusters in the gas phase often exhibit “magic numbers,” corresponding to enhanced abundances at specific cluster sizes, typically attributed to particularly stable geometric arrangements. Here, we combine electrospray ionization mass spectrometry (ESI-MS) with quantum chemical calculations to investigate the structure and stability of protonated glycine clusters. The experimental mass spectrum reveals pronounced magic numbers at cluster sizes n = 3 and n = 6. To elucidate their origin, we performed a systematic computational investigation of glycine clusters up to n = 7, including global structure searches, high-level electronic structure calculations, and thermal stability simulations. Our calculations show that clusters with n = 2, 4, and 5 are predominantly composed of canonical glycine molecules; the n = 7 clusters are composed of both neutral and zwitterionic glycine molecules, whereas the hexamer is the first cluster size for which fully zwitterionic structures become thermodynamically preferred. This neutral-to-zwitterionic transition gives rise to a highly cooperative hydrogen-bonding network and is accompanied by a pronounced increase in thermal stability, providing a natural explanation for the exceptional abundance of the hexamer. In contrast, the enhanced abundance of the trimer is consistent with kinetic stabilization under electrospray ion-source conditions rather than with the thermodynamic stability of its global free-energy minimum. These findings provide molecular-level insight into the emergence of magic numbers in glycine clusters and the onset of zwitterionic stabilization in finite molecular assemblies.