The relative silver(I) ion binding energies of 19 ␣-amino acids have been measured by means of the kinetic method. In general, they are similar to the relative copper(I) ion binding energies of corresponding amino acids although there are differences that can be accounted for by differences in silver(I) and copper(I) chemistry. The correlation with proton basicities is comparatively poorer. Again, the differences between silver(I) and proton binding can be attributed to differences in silver(I) and proton chemistry. The relative silver(I) binding energies measured are best described as relative basicities or ⌬⌬G°A g 's. The observed internal consistency during construction of a silver(I) ion basicity ladder implies that ⌬⌬S°A g is approximately zero except when histidine and lysine are involved. For 16 ␣-amino acids, their relative silver(I) ion basicities Ϸ relative silver(I) ion affinities or ⌬⌬G°A g Ϸ ⌬⌬H°A g . (J Am Soc Mass Spectrom 1998, 9, 760 -766) © 1998 American Society for Mass Spectrometry T he bio-inorganic chemistry of the silver(I) ion is rich and fascinating. The silver(I) ion has long been used as a bactericide in the form of eye drops for newborns [1,2]. Some of its complexes display remarkable antimicrobial activities [3,4]. The metallothioneins, a class of small proteins believed to be responsible for heavy-metal detoxification in mammals, exhibit very high affinity for Ag(I) [5][6][7]. The silver(I) ion binds relatively strongly to peptides and proteins; collision-induced dissociation of these complexes in the gas phase yields abundant Ag(I)-bound product ions [8].We report in this article the first measurement of the relative gas-phase silver(I) ion binding energies of 19 essential ␣-amino acids. Measurements of gas-phase binding energies, especially affinities, of biological ligands for small ions, including protons [9 -23], alkalimetal ions [24], and recently Cu(I) [25], are often made with the desire to know the fundamental, intrinsic binding in the absence of water-an environment which approximates that in the interior of proteins. The kinetic method, developed by Cooks and co-workers [26 -30], is a particularly effective method for measuring relative ion binding energies of amino acids and peptides because it does not require generating a population of nonvolatile neutral ligands in the gas phase. It is based on measuring the logarithm of the relative abundance of the product ions arising from the dissociation of an ion-bound heterodimer of the ligands, which is proportional to the logarithm of the relative rate of dissociation of the two reaction channels, to estimate the relative binding energies of the two ligands for the ion:where M is the central ion, B i is a reference base whose binding energy to M is known, and B is the unknown base whose binding energy is being measured. AccordAddress reprint requests to Dr.