Carboxamides are simple model compounds for peptides and proteins all sharing the polar amide group. The capability of this group to participate in hydrogen bonding is well known and is responsible for the tertiary structures of proteins. However, until now only the proton affinities (PA) of a few simple aliphatic amides are known.

Protonated amides cluster efficiently even in the diluted gas phase by formation of proton bound heterodimers with other bases. This has been used to determine the PAs of aliphatic primary amides and diamides and of the tertiary N,N-dimethyl derivatives by the "kinetic method". By this method, the unimolecular fragmentation of proton bound heterodimers of compound M with a series of bases B is observed by tandem mass spectrometry. During the decomposition of metastable [M··H⁺··B] the proton stays dominantly with the more basic component, which can be used to bracket the PA of M. To evaluate the effect of the acyl group on the PA the primary and tertiary amides of some typical aliphatic carboxylic acids with linear, branched and cyclic acyl groups were studied. As expected the PA of a tertiary N,N-dimethylamide is generally 46±1 kJ/mol greater than the PA of the corresponding primary amide. In both series the PA increases with the number of C atoms of the acyl group and approaches rather quickly limiting values of 887 kJ/mol and 933 kJ/mol.

The PA of the primary and tertiary diamides of linear aliphatic dicarboxylic acids were determined to examine the effect of an intramolecular H⁺ bridge on the PA. The ability to form an intramolecular hydrogen bond on protonation increases distinctly the PA. This effect is seen clearly for all saturated open chain diamides with the exception of malondiamide, and becomes most obvious from the PA of the diamide of succinic acid, maleic acid (both PA 930 kJ/mol) and fumaric acid (PA 865 kJ/mol). Only the former protonated diamides form a proton bridge of similar geometry. The maximum value observed for the primary and tertiary diamides in this series is 949 kJ/mol and 967 kJ/mol.

Finally, the PA of the stereoisomers of the primary and tertiary diamides of cyclopentane- and cyclohexane dicarboxylic acids were determined. Again, the PA of these diamides is dominated by the formation of a proton bridge between the two amide groups. In the case of the rather rigid diamides of cyclopentane dicarboxylic acids this is only possible for the cis-isomers, which accordingly exhibit increased PA. Similar effects are observed for the diamides of the more flexible cyclohexane dicarboxylic acids. Here, a proton bridge is formed even in the case of the cis-isomers of the 1,3- and 1,4-diacids in spite of the unfavorable 1,3-diaxial orientation or boot conformation of the cyclohexane ring necessary for a proton bridge between the two amide groups.