Polyhedron | 2019
Potentiometric and spectroscopic studies of the complex formation between copper(II) and Gly-Leu-Phe or Sar-Leu-Phe tripeptides
Abstract
Abstract Metal complexes involving a chelation between copper(II) and the tripeptides, sarcosyl- l -leucyl-phenylalanine (Sar-Leu-Phe) and glycyl- l -leucyl-phenylalanine (Gly-Leu-Phe), have been identified as potential therapeutic drugs for rheumatoid arthritis. However, in solution the speciation and exact coordination of these tripeptides to copper(II) is unknown and as a result this was investigated using glass electrode potentiometry, ultraviolet–visible spectrophotometry, infrared spectroscopy and 1H NMR and CW EPR spectroscopies. The same basicity was found for the terminal amine of both tripeptides, but the methyl group on Sar decreased the copper(II) complex stability constants by 0.38–1.67\u202flog units. Four species: ML, MLH-1, ML2H-1 and MLH-2 were found for both tripeptides in the pH range 2–11. The dissociated protons are from the amide groups. Room temperature and frozen solution EPR spectra support the existence of MLH-1, MLH-2 and ML2H-1 (a large excess was required for the ML2H-1 species). The two species, MLH-2 and ML2H-1, have a CuN3O equatorial chromophore, which therefore produce similar room temperature EPR spectra, with similar magnetic parameters. Frozen solution EPR spectra revealed different anisotropic magnetic parameters in axial symmetry, thus suggesting the presence of two different geometries. The lower g|| and the higher A|| values indicate that the geometry of the MLH-2 complexes tends more towards square planar, instead of the usual expected tetragonally elongated octahedral geometry. Copper(II) could coordinate to each tripeptide via an amine-N, two amide-Ns, two carbonyl-Os and a carboxyl-O. The proposed coordination modes were validated using quantum mechanical calculations.