Sterically Stabilized End-On Superoxocopper(II) Complexes and Mechanistic Insights into Their Reactivity with O–H, N–H, and C–H Substrates

Abstract

Instability of end-on superoxocopper(II) complexes, with respect to conversion to the corresponding peroxobridged complexes, has largely constrained their study to very low temperatures (< -80 C). This limits their kinetic capacity to oxidize substrates. In response, we have developed a series of ligand systems bearing bulky aryl substituents that are primarily directed away from the metal centre, Ar3-TMPA (Ar = tpb, dpb, dtbpb), and used them to support [Cu I (Ar3-TMPA)(NCMe)] + copper(I) complexes. Solutions of all three react with O2 to yield [Cu II ( 1 -O2 )(Ar3-TMPA)] + complexes that are stable against dimerization at all temperatures. Full binding of O2 is observed at sub-ambient temperatures and can be reversed by warming. The onset of oxygenation is ligand dependent, but can be observed at 25 C in the case of Ar = tpb and dpb. Furthermore, all three [Cu II ( 1 -O2 )(Ar3-TMPA)] + complexes are stable against self-decay at temperatures -20 C. This provides a wide temperature window over which these complexes can be studied, which was exploited by performing extensive reaction kinetics measurements for [Cu II ( 1 -O2 )(tpb3-TMPA)] + with a broad range of O-H, N-H, and C-H bond substrates. This includes correlation of second order rate constants (k2 values) versus oxidation potentials (Eox) for a range of phenols (i.e., a Marcus plot), construction of Eyring plots, and temperature-dependent kinetic isotope effect (KIE) measurements. The data obtained indicates that reaction with all substrates proceeds via H-atom transfer (HAT) to [Cu II ( 1 -O2 )(tpb3-TMPA)] + . In addition, evidence suggests that HAT reaction with the phenols studied proceeds with significant charge transfer, and that it involves full tunelling of both H and D atoms in the case of 1,2-diphenylhydrazine (DPH) and 4methoxy-2,6-di-tert-butylphenol (MeO-ArOH). Consistent with expectations for HAT, large entropic barriers ( S ) were measured for the substrates MeO-ArOH, DPH, triphenylhydrazine (TPH), and 1-benzyl-1,4-dihydronicotinamide (BNAH). Despite having the lowest X-H bond dissociation energy (BDE) amongst these substrates, the C-H substrate BNAH exhibits both the largest S and the second largest enthalpic barrier ( H ) to reaction. This is congruent with the expectation that oxidation of C-H bonds is kinetically challenging and the experimental observation that [Cu II ( 1 -O2 )(tpb3-TMPA)] + is only able to oxidize very weak C-H bonds, whereas it can oxidize moderately strong N-H bonds. ASSOCIATED CONTENTInformation. Experimental and synthetic procedures, X-ray crystallographic data collection and structural parameters, additional UV-Vis and resonance Raman spectra, and reaction kinetics data (PDF). Crystal structures of copper(II) complexes (CIF).This material is available free of charge via the Internet at http://pubs.acs.org.

Generation and Aerobic Oxidative Catalysis of a Cu(II) Superoxo Complex Supported by a Redox-Active Ligand

“…For instance, proposed GO enzymatic cycles involve a H-atom transfer to a coordinating modified tyrosyl radical residue along with electron transfer to the Cu center as the active alcohol oxidizing steps, with O 2 serving to regenerate the oxidized active site . Conversely, studies of lytic polysaccharide monooxygenase (LPMO) active sites implicate a more direct substrate oxidizing role for O 2 -derived species such as Cu oxyl or Cu hydroxo species. , While several Cu–superoxo complexes have been shown to initiate the oxidation of moderately strong C–H and O–H bonds (BDEs of ∼70–83 k cal –1 mol –1 ), most model systems have not been able to mimic the reactivity of monooxygenase enzymes, which commonly activate C–H bonds with strengths of up to 87 k cal –1 mol –1 . − …”

A caged tris(2-pyridylmethyl)amine ligand equipped with a Ctriazole–H hydrogen bonding cavity

“…2 Many efforts have been dedicated to the development of artificial Cu ligands able to generate and stabilize such metastable intermediates. Among them, the tris(2-pyridylmethyl)amine ( TPA ) ligand has been widely used as a scaffold for mimicking the first coordination sphere in the structural and functional models of copper, 3 but also iron, 4 mono-oxygenases. Interestingly, incorporating intramolecular H-bonding secondary spheres into the TPA ligand was reported as an efficient strategy to stabilize mononuclear hydroperoxo [(L)Cu II –OOH] + , 5 binuclear peroxodicopper [{(L)Cu II } 2 (O 2 2− )], 6 or end-on superoxo [(L)Cu II –O 2 ˙ − ] 7 copper–dioxygen intermediates.…”

Electrostatic Contributions to the Stability of an End-on Cupric Superoxide

“…A commonly invoked intermediate in enzymatic copper oxidases [1][2][3] and oxygenases 1,[4][5][6] is the end-on (η 1 ) cupric superoxide (Cu II -O2 •1-), which activates substrates through initial hydrogen atom transfer (HAT) reactions. This broad biological basis of reactivity has inspired the synthesis of molecular Cu II -O2 •1species, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] but the study and use of these complexes is complicated by their instabilities with respect to formation of di(cupric)-μ-1,2-peroxides (Figure 1). The development of strategies for improving the lifetimes of Cu II -O2 •1complexes, while maintaining their oxidizing capacity, is expected to lead to the development of new catalysts based on the reactive superoxide moiety.…”

“…In the earliest studies, short-lived Cu II -O2 •1were detected by stopped-flow UV-vis spectroscopy under cryogenic conditions (-80 to -120 °C). 8,9,21 Strategies developed since then for increasing the lifetimes of these complexes have focused on i) increasing the steric bulk in the secondary coordination spheres, 12,13,15,16,18,20 ii) cathodically shifting the Cu I /Cu II redox potentials, 9 and iii) incorporating intramolecular hydrogen bonding residues into the secondary coordination spheres (Figure 1). 7,19 Molecular-scale electrostatic effects are gaining attention for their ability to meaningfully impact the chemistry of organic, transition metal, and enzymatic systems.…”

“…precluding the formation of di(cupric)-µ-peroxides (decreasing k2 in Figure 1), which has allowed for their observation at higher temperatures but not necessarily with higher binding affinities. 12,13,15,16,18,20 Alternatively, several studies have successfully imparted increased binding affinity of O2 (Keq in Figure 1). Derivatized TMPA ligands containing H-bonding moieties in the secondary coordination spheres were able to support cupric superoxides that were found to be persistent at -135 °C (t1/2 > 30 h).…”