Cyclamic acid sweetener: a pulsed laser ablation rotational study

Cyclamic acid is a common non-caloric artificial sweetener, but the exact molecular mechanisms behind its interaction with sweet taste receptors have been obscured by environmental disturbances in condensed phases. To reveal its inherent structure-activity relationship, we present the first gas-phase structural analysis of neutral cyclamic acid using Laser Ablation Chirped-Pulse Fourier Transform Microwave (LA-CP-FTMW) spectroscopy combined with computational modeling. Three distinct conformers were experimentally detected and definitively identified as two equatorial and one axial structure. We show that the dominance of the equatorial forms aligns with the AH–B–γ “sweetness triangle” and fits the bioactive shape required by the T1R2/T1R3 receptor. This natural pre-organization could prevent a thermodynamically costly induced-fit adaptation. This fact could explain cyclamate's strong sweet taste at a molecular level, highlighting gas-phase spectroscopy as a vital tool for designing new flavor enhancers.