Experimental validation of theoretical potassium and sodium cation affinities of amides by mass spectrometric kinetic method measurements

In this study the theoretical Gaussian‐2 K + /Na + binding affinities (enthalpies) at 0 K (in kJ mol −1 ) for six amides in the order: formamide (109.2/138.5) <  N ‐methylformamide (117.7/148.6) < acetamide (118.7/149.5) <  N,N ‐dimethylformamide (123.9/156.4) <  N ‐methylacetamide (125.6/157.7) <  N,N ‐dimethylacetamide (129.2/162.6), reported previously (Siu et al ., J. Chem. Phys. 2001; 114: 7045–7051), were validated experimentally by mass spectrometric kinetic method measurements. By monitoring the collision‐induced dissociation (CID) of K + /Na + ‐bound heterodimers of the amides, the relative affinities were shown to be accurate to within ±2 kJ mol −1 . With these six theoretical K + /Na + binding affinities as reference values, the absolute K + /Na + affinities of imidazole, 1‐methylimidazole, pyridazine and 1,2‐dimethoxyethane were determined by the extended kinetic method, and found to be consistent (to within ±9 kJ mol −1 ) with literature experimental values obtained by threshold‐CID, equilibrium high‐pressure mass spectrometry, and Fourier transform ion cyclotron resonance/ligand‐exchange equilibrium methods. A self‐consistent resolution is proposed for the inconsistencies in the relative order of K + /Na + affinities of amides reported in the literature. These two sets of validated K + and Na + affinity values are useful as reference values in kinetic method measurements of K + /Na + affinity of model biological ligands, such as the K + affinities of aliphatic amino acids. Copyright © 2004 John Wiley & Sons, Ltd.