Effects of Thioether Substituents on the O₂ Reactivity of β-Diketiminate−Cu(I) Complexes:  Probing the Role of the Methionine Ligand in Copper Monooxygenases

Abstract

The activation of dioxygen by dopamine β-monooxygenase (DβM) and peptidylglycine α-hydroxylating monooxygenase (PHM) is postulated to occur at a copper site ligated by two histidine imidazoles and a methionine thioether, which is unusual since such thioether ligation is not present in other O 2 -activating copper proteins. In order to assess the possible role of the thioether ligand in O 2 activation by DβM and PHM, two new ligands comprising β-diketiminates with thioether substituents were synthesized and Cu(I) and Cu(II) complexes isolated. The Cu(II) compounds are monomeric and exhibit intramolecular thioether coordination. While the Cu(I) complexes exhibit a multinuclear topology in the solid state, variable temperature 1 H NMR studies implicate equilibria in solution, possibly including monomers with intramolecular thioether coordination that are structurally defined by DFT calculations. Low temperature oxygenation of solutions of the Cu(I) complexes generates stable 1:1 Cu/O 2 adducts, which on the basis of combined experimental and theoretical studies adopt side-on "η 2 " structures with negligible Cu-thioether bonding and significant peroxo-Cu(III) character. In contrast to previously reported findings with related ligands lacking the thioether group, however, purging the solutions of the thioether-containing adducts with argon results in conversion to bis(μ-oxo)dicopper(III) species. A role for the thioether in promoting loss of O 2 from the 1:1 Cu/O 2 adduct and facilitating trapping of the resulting Cu(I) complex to yield the bis (μ-oxo) species is proposed and the possible relevance of this role to that of the methionine in the active sites of DβM and PHM is discussed.

Mononuclear Cu–O2 Complexes: Geometries, Spectroscopic Properties, Electronic Structures, and Reactivity

“…However, only sideon coordination upon oxygenation of a Cu(I) precursor was indicated by the spectroscopic data [ν(O-O) ) 994 cm -1 ] and by theoretical calculations, which predicted only weak binding of the thioether sulfur atom to copper ( Figure 6). 36 Further ligand perturbations considered with computational modeling involved the introduction of an ancillary ligand whose steric and/or electronic requirements might bias the binding of O 2 in 3 to favor end-on coordination; again, however, no simple, solventlike ligand could be identified that led to the prediction of a thermodynamically stable end-on oxygenated product. 37 Finally, given that the end-on geometry is likely to have more Cu(II)-superoxide character that would be stabilized relative to the Cu(III)-peroxide alternative by a less electron donating supporting ligand, we examined versions of the -diketiminate in 3 with one or two CF 3 replacements for the methyl groups on the backbone.…”

Characterization of the structure and reactivity of monocopper–oxygen complexes supported by β‐diketiminate and anilido‐imine ligands

“…Singlet and triplet states were treated at restricted (RDFT) and unrestricted (UDFT) levels of theory, respectively, in keeping with the established methodology for the types of copper-oxygen complexes described herein. 13,28,29,36,37 In addition, UDFT methods were used for doublets and optimizations of Cu(III)-hydroxide complexes. Basis sets utilized included the lacvp** effective core potential basis for Cu [38][39][40] and the double-plus polarization (DZP) 6-31G** basis for all other atoms.…”

“…Final electronic energies for singlet states for the full ligand systems are obtained by summing the SCF energies from DFT calculations on the full L 1 and L 2 ligand systems with D for the corresponding simplified model. This methodology has proved capable of predicting both the proper singlet-triplet state orderings 28,29,37 and the kinetics of oxygenation in the L 1 system. 28 To facilitate the determination of D along the reaction path for 1:1…”

Copper‐Catalyzed Rearrangement of Tertiary Amines through Oxidation of Aliphatic CH Bonds in Air or Oxygen: Direct Synthesis of α‐Amino Acetals

“…[3,4] After electron-transfer, deprotonation, and electron-transfer processes, iminium ion C is produced. Iminium ion C is then converted into enamine D by deprotonation.…”