Functional group interactions and substituent effects of o-, m-and p-aminobenzoic acids were examined in a quadruple ion trap by evaluation of proton-transfer a d methylene substitution reactions. An electron-withdrawing carboxylic acid group can enhance or reduce the gas-phase basicity of aniline depending on its location and ability to participate directly in proton bridging. In fact, the gas-phase basicity of o-aminobenzoic acid is enhanced by -7 kcal mol-' relative to the metu and para isomers in which the substituents do not have cooperative functional group interactions. Collisionally activated dissociation studies of deuterium-labeled ions provide evidence of proton migration from the amino group to the carboxylic acid group prior to fragmentation. Results of semi-empirical molecular orbital calculations provided structures for the various protonated aminobenzoic acids. For oaminobenzoic acid, the proton bridges between the acid and amine groups. I N T R O D U C T I O NHydrogen bonding is among the most important types of interactions in organic and biological chemistry. '-'Numerous recent studies have begun to address the significance of hydrogen bonding interactions in gas-phase ions, especially with respect to the influence on gasphase basicities, cluster formation and s~l v a t i o n .~~~' The evaluation of intramolecular hydrogen bonds has become increasingly common recently owing to the advent of electrospray ionization and the formation of multiply protonated molecules, such as proteins. Studies have shown that when two or more functional groups coexist in a compound, the interaction among neighboring functional groups affects the physical properties and chemical rea~tivities,''-'~ such as in the well known ortho effect.' 9-25 Therefore, it is reasonable to predict that the basicity of a compound depends not only on the nature of the functional groups, but also on the relative positions and orientations of the groups within the compound. For example, it is well accepted that diamines typically have greater gas-phase basicities than amines because of the ability of a protonated diamine to undergo cyclization via proton bridging between the two amine groups7 It has been found that the strain energy in cyclic protonated diamines ranges from 2.5 to 10.4 kcal mol-I (1 kcal = 4.184 kJ) depending on the ring size, whereas the formation of the intramolecular hydrogen bonds can stabilize the ions by up to 20 kcal mol-'." Another group reported the cyclization enthalpy resulting from proton bridging between two interacting amine groups to range from -5 to -17 kcal mol-' depending on the geometry of the hydrogen bond. l 6 Additionally, from measurements on the proton-transfer equilibria of a series of polyethers, it was found that basic molecules that could participate in multi-coordination of a proton have enhanced proton affinities but suffer a decrease in entropy owing to the enforced organization of the polyether structures." For instance, the enthalpy of the intramolecular hydrogen bond in protonated poly...