The sequence and conformational effects on the gas-phase acidities of peptides have been studied by using two pairs of isomeric cysteine-polyglycine peptides, CysGly 3,4 NH 2 and Gly 3,4 CysNH 2 . The extended Cooks kinetic method was employed to determine the gas-phase acidities using a triple quadrupole mass spectrometer with an electrospray ionization source. The ion activation was achieved via collision-induced dissociation experiments. The deprotonation enthalpies (⌬ acid H) were determined to be 323.9 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 319.2 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 333.8 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 321.9 Ϯ 2.8 kcal/mol (Gly 4 CysNH 2 ), respectively. The corresponding deprotonation entropies (⌬ acid S) of the peptides were estimated. The gas-phase acidities (⌬ acid G) were derived to be 318.4 Ϯ 2.5 kcal/mol (CysGly 3 NH 2 ), 314.9 Ϯ 2.3 kcal/mol (CysGly 4 NH 2 ), 327.5 Ϯ 2.1 kcal/mol (Gly 3 CysNH 2 ), and 317.4 Ϯ 2.8 kcal/mol (Gly 4 CysNH 2 ), respectively. Conformations and energetic information of the neutral and anionic peptides were calculated through simulated annealing (Tripos), geometry optimization (AM1), and single point energy calculations (B3LYP/6-31ϩG(d)), respectively. Both neutral and deprotonated peptides adopt many possible conformations of similar energies. All neutral peptides are mainly random coils. The two C-cysteine anionic peptides, Gly 3,4 (Cys-H) Ϫ NH 2 , are also random coils. The two N-cysteine anionic peptides, (Cys-H) Ϫ Gly 3,4 NH 2 , may exist in both random coils and stretched helices. The two N-cysteine peptides, CysGly 3 NH 2 and CysGly 4 NH 2 , are significantly more acidic than the corresponding C-terminal cysteine ones, Gly 3 CysNH 2 and Gly 4 CysNH 2 . The stronger acidities of the former may come from the greater stability of the thiolate anion resulting from the interaction with the helix-macrodipole, in addition to the hydrogen bonding interactions. (J Am Soc Mass Spectrom 2010, 21, 603-614)

The use of chiral Ni(II)-salen derivatives was examined in mediated electrohydrocyclization (EHC) reactions. Cyclic voltammetry established the existence of a catalytic current. Bulk electrolysis revealed a slight change in the diastereoselectivity of the cyclizations. Density functional theory (DFT) computational studies showed that Ni(II)-salen and Zn(II)-salen were the best metal-salens for electron transfer, while Co(II)-salen and Cu(II)-salen would likely be ineffective for this purpose. Electron transfer was both considerably more thermodynamically and kinetically (whether through an inner or outer sphere pathway) favorable with Ni(II)salen and Zn(II)-salen. Computational data also suggests Ni(II)-salen to be preferred for promoting inner sphere electron transfer, due in part to the ligand-centered reduction of Ni(II)-salen, and thus for affecting stereoselectivity in mediated EHC reactions.

The use of chiral Ni(II)-salen derivatives was examined in mediated electrohydrocyclization reactions. Cyclic voltammetry established the existence of a catalytic current. Bulk electrolysis revealed a slight change in the diastereoselectivity of the cyclizations. Computational studies were conducted that showed that Ni(II) and Zn(II) were the best metals for electron transfer, while the analogous Co(II) and Cu(II) compounds would likely not result in effective electron transfer.