Using NMR spectroscopy, the conformational studies of two fluoroethylsulfonamides (N-(2-fluoroethyl)-p-tolylsulfonamide (1) and N-(2-fluoroethyl)trifluoromethanesulfonamide (2)) revealed that fluorine gauche effects are a function of ionization. While acids 1 and 2 exhibited gauche effects (with gauche populations of 87% and 92% in DMSO-d6, respectively), their anions, on the other hand, preferred the anti conformer (with gauche populations of 35% and 55%, respectively). The ability of these compounds to undergo conformational changes as a function of ionization enabled their application as molecular probes (standards) for determining the acidity (pKa) of organic compounds in DMSO, which was achieved with the aid of the equation Krel = [(3JAH - 3Jobs)/(3Jobs - 3JA)]2, where Krel is the ratio of ionization constants of two acids (standard and test acids), 3JAH and 3JA are the proton-fluorine vicinal coupling constants of the standard acid and its anion, respectively, and 3Jobs represents the proton-fluorine vicinal coupling constant observed at the midpoint of an acid-base equilibrium. As a means of demonstrating its utility, this equation accurately calculated the ionization constants (Ka) of several organic compounds in DMSO. Taking advantage of fluorine's unique gauche effect as a strategy for molecular design has the potential to open a new frontier in structural chemistry.