Complex Formation and Redox Reactions in Copper–Pterin Cofactor Systems. Possible Relevance to Phenylalanine Hydroxylase

Abstract

Abstract With a view to understanding better the redox reactions between the metal center and the pterin cofactor in phenylalanine hydroxylase (PAH) and the effects of possible sulfur coordination to the metal center, we isolated model copper(II) complexes of 2,2′-bis(2-pyridylmethyl)amine (dpa), S-ethyl-N-(2-pyridylmethyl)aminoethanethiol (pat), and pterin-6-carboxylate (ptc), [Cu(dpa)(ptc)]·H2O·CH3OH (1), [Cu(pat)(Cl)]Cl·H2O (2), and [Cu(pat)(ptc)]·3H2O (3), of which 1 and 3 contained ptc as a cofactor model. These binary and ternary Cu(II) complexes were studied by X-ray diffraction, spectroscopic, and electrochemical methods. Redox reactions between Cu(II) complexes ([Cu(dpa)]2+ or 1) and tetrahydropterins (5,6,7,8-tetrahydro-6,7-dimethylpterin (h4dmp) or 5,6,7,8-tetrahydropterin-6-carboxylate (h4ptc)) were also investigated by time-resolved spectroscopic methods. The molecular structures of 1, 2, and 3 showed that dpa and pat occupy three equatorial positions and that ptc in 1 and 3 is vertically coordinated. Complexes 2 and 3 exhibited relatively high redox potentials due to thioether sulfur coordination (E1/2 = −0.06 and −0.18 V vs. Ag/AgCl, respectively) in contrast to [Cu(dpa)]2+ and 1 (E1/2 = −0.32 and −0.39 V, respectively). Coordination of h4dmp and h4ptc to the Cu(II) center of [Cu(dpa)]2+ and 2 to form ternary complexes was detected by the ESR spectra with the use of the rapid mix-freeze-quenching technique; subsequent redox reactions were concluded from the absorption spectral changes.