Synthesis, Characterization, and Reaction Studies of Pd(II) Tripeptide Complexes.

The aqueous synthesis of Pd(II) complexes with alkylated tripeptides led to the hydrolysis of the peptides at low pH values and mixtures of complexed peptides were formed. A non-aqueous synthetic route allowed the formation and isolation of single products and their characterization. Pd(II) complexes with α-Asp(OR)AlaGly(OR), ß-Asp(OR)AlaGly(OR), and TrpAlaGly(OR) (R = H or alkyl) as tri and tetradentate chelates were characterized. The tridentate coordination mode was accompanied by a fourth monodentate ligand that was shown to participate in both ligand exchange reactions and a direct removal to form the tetradentate coordination mode. The tetradentate coordination revealed a rare a hemi labile carbonyl goup coordination mode to Pd(II). Reactivity with small molecules such as ethylene, acids, formate, and episulfide was investigated. Under acidic conditions and in the presence of ethylene; acetaldehyde was formed. The Pd(II) is a soft Lewis acid and thiophilic and the complexes abstract sulfur from episulfide at apparent modest catalytic rates. The complexes adopt a square planar geometry according to a spectroscopic analysis and DFT calculations that were employed to evaluate the most energetically favorable coordination geometry and compared with the observed infrared and NMR data.

Directed coordination study of [Pd(en)(H2O)2]2+ with hetero-tripeptides containing C-terminus methyl esters employing NMR spectroscopy.

Alkylation of the C-terminus acids in small peptides allows direction to amine and amide coordination, while changing the peptide composition to form tetradentate κ4[n,5,5], where n = 5-, 6-, 7-, or 8-membered ring coordination geometries, can be achieved. The alkylated tripeptide ligands, TrpAlaGly(OMe), ß-Asp(OtBu)AlaGly(OMe), Asp(OtBu)AlaGly(OMe), and the fully methylated GSH, γ-Glu(OMe)Cys(SMe)Gly(OMe), were synthesized and their coordination properties to [Pd(en)(H2O)2]2+ were studied. pH-dependent coordination was analyzed by NMR spectroscopy and the coordination to the alkylated tripeptides at selected pH values inferred from their NMR spectra. If selective coordination of amine/amide donors results in metal complexation, allowing for flexible and adjustable ligand frameworks, then this strategy could potentially be extended to other metal ions and peptide system.