Positive mode electrospray mass spectrometry was used to investigate complexes of cysteine and selenocysteine with the metallo-drug Auranofin and the analogous chlorotriethylphosphine gold. Evidence for all the complexes, with the exception of the Auranofin–selenocysteine complex, was obtained. Several fragmentation products were examined and their proposed structures reported. Structural details of many experimentally observed ions including [Auranofin + H]+, [(CH3CH2)3P–Au–cysteine]+ and [(CH3CH2)3P–Au–methylselenocysteine]+ were examined by means of hybrid density functional theory at the B3LYP/DZVP level. Structural information and relative free energies are presented for several isomers of each ion considered.Formation and fragmentation of Auranofin complexes with cysteine and seleocysteine.

The complexes of Ag+ with the peptides MetGly, ProGly, GlyPro, GlyHis and GlyProAla were investigated using hybrid density functional theory at the B3LYP/DZVP level. The silver ion binding free energies at 298 K to each of these peptides was calculated to be 60.8, 52.0, 54.3, 71.2 and 63.3 kcal mol−1, respectively. Structural information and relative free energies are presented for several isomers for each of the five complexes. Each of the global minima found for the five complexes is a charge-solvated ion. An important finding is that the Ag+–ProGly is the only complex where a salt bridge structure is energetically favored occurring at 4.0 kcal mol−1 higher in free energy than the global minimum. The Ag+ ion in this salt bridge structure is attached to the carboxylate anion of zwitterionic ProGly in which the terminal amino nitrogen is protonated. For all the other complexes studied, the salt bridge structure occurs at much higher energies. All the dipeptide complexes with Ag+, but one, exhibit a di- or tri-coordinate metal where the sites of attachment are amino and carbonyl groups. However, the highest coordination numbers are not always the global minima due to steric costs. The global minimum of the Ag+–GlyProAla complex is the only structure found in this study where the metal is tetra-coordinated, binding to the terminal amino nitrogen and all three carbonyl oxygen atoms. Silver binding to sulphur and imidazole nitrogen atoms of MetGly and GlyHis, respectively, are present in the three most energetically favored species in each of these cases.The complexes of Ag+ with five peptides were investigated using B3LYP/DZVP. Silver ion affinity and binding free energy at 298 K is presented for to each of these peptides. Structural information and relative free energies are presented for several isomers for each of the five complexes.