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Intramolecular hydrogen atom transfer (HAT) was examined in homocysteine (Hcy) thiyl radical/alkali metal ion complexes in the gas phase by combination of experimental techniques (ion-molecule reactions and infrared multiple photon dissociation spectroscopy) and theoretical calculations. The experimental results unequivocally show that metal ion complexation (as opposed to protonation) of the regiospecifically generated Hcy thiyl radical promotes its rapid isomerisation into an α-carbon radical via HAT. Theoretical calculations were employed to calculate the most probable HAT pathway and found that in alkali metal ion complexes the activation barrier is significantly lower, in full agreement with the experimental data. This is, to our knowledge, the first example of a gas-phase thiyl radical thermal rearrangement into an α-carbon species within the same amino acid residue and is consistent with the solution phase behaviour of Hcy radical., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Potential consequences of the binding of the anticancer drug cisplatin to various biomolecules in the cell have been investigated by using a combined density functional theory and continuum dielectric model approach. Since the amine ligands remain coordinated at the metal upon formation of the most frequent DNA adducts, whereas they were found to be displaced from the metal upon formation of drug metabolites, we have analyzed the factors governing amine loss from platinum(II) complexes as a possible pathway of cisplatin inactivation. The calculations systematically show the effect of 1) the trans ligand, 2) the charge of complex, 3) the nucleophile, and 4) the environment on the thermodynamic instability and kinetic lability of the platinum-amine bonds. After initial binding of cisplatin hydrolysis products to thioethers or thiols, loss of the amine trans to this sulfur ligand rather than replacement of the sulfur ligand itself by other nucleophiles like guanine-N7 is predicted to be the predominant reaction. The results of this study contribute to an understanding of the modes of cisplatin inactivation prior to DNA binding, for example, by elevated glutathione levels in cisplatin-resistant cancer cells.

The potassium cation affinities (PCAs) of 136 ligands (20 classes) in the gas phase were established by hybrid density functional theory calculations (B3-LYP with the 6-311+G(3df,2p) basis set). For these 136 ligands, 70 experimental values are available for comparison. Except for five specific PCA values-those of phenylalanine, cytosine, guanine, adenine (kinetic-method measurement), and Me(2)SO (by high-pressure mass spectrometric equilibrium measurement)-our theoretical estimates and the experimental affinities are in excellent agreement (mean absolute deviation (MAD) of 4.5 kJ mol(-1)). Comparisons with previously reported theoretical PCAs are also made. The effect of substituents on the modes of binding and the PCAs of unsubstituted parent ligands are discussed. Linear relations between Li+/Na+ and K+ affinities suggest that for the wide range of ligands studied here, the nature of binding between the cations and a given ligand is similar, and this allows the estimation of PCAs from known Li+ and/or Na+ affinities. Furthermore, empirical equations relating the PCAs of ligands with their dipole moments, polarizabilities (or molecular weights), and the number of binding sites were established. Such equations offer a simple method for estimating the PCAs of ligands not included in the present study.