Isotopic Probing of Molecular Oxygen Activation at Copper(I) Sites

Abstract

Copper-dioxygen (CuO2) adducts are frequently proposed as intermediates in enzymes, yet their electronic and vibrational structures have not always been understood. [Cu(eta1-O2)TMG3tren]+ (TMG3tren = 1,1,1-tris{2-[N2-(1,1,3,3-tetramethylguanidino)]ethyl}amine) features end-on (eta1) O2 coordination in the solid state. Described here is an investigation of the compound's solution properties by nuclear magnetic resonance spectroscopy, density functional calculations, and oxygen isotope effects. The study yields two major findings. First, [Cu(eta1-O2)TMG3tren]+ is paramagnetic due to a triplet electronic structure; this is in contrast to other copper compounds where O2 is bound in a side-on manner. Second, the oxygen equilibrium isotope effect upon O2 binding to copper(I) (18O EIE [triple bond] K(16O16O)/K(16O18O) = 1.0148 +/- 0.0012) is significantly larger than those determined for iron and cobalt eta1-O2 adducts. This result is suggested to reflect greater ionic (CuII-O2-I) character within the valence bond description. A revised interpretation of the physical origins of the 18O EIEs upon O2 binding to redox metals is also advanced along with experimental data that should be used as benchmarks for interpreting 18O kinetic isotope effects upon enzyme reactions.

Theoretical Exploration of the Oxidative Properties of a [(trenMe1)CuO2]+ Adduct Relevant to Copper Monooxygenase Enzymes: Insights into Competitive Dehydrogenation versus Hydroxylation Reaction Pathways

“…This is in agreement with the experimental data reported for the related [(tren TMG )CuO 2 ] + adduct, which has an O À O distance of 1.280 , [45] and was recently shown to have a triplet fundamental state. [12] Starting from the [(tren…”

“…Nevertheless, subclasses of enzymes that use the same strategies can be identified. Among them, two monooxygenases, [12] namely, peptidylglycine a-hydroxylating monooxygenase (PHM) and dopamine b-hydroxylase (DbH; Figure 1, middle) appear particularly interesting, as both involve a common strategy relying on two noncoupled mononuclear copper centers separated by a solvent cleft (Figure 1, left). Many theoretical investigations have been devoted to these systems and have addressed the capability of various oxygenated intermediates such as copper hydroperoxo ([Cu II A C H T U N G T R E N N U N G ( À OOH)] + ), [13][14][15][16] copper oxyl A C H T U N G T R E N N U N G ([Cu II A C H T U N G T R E N N U N G (OC À )] + ), [15][16][17] or copper oxo ([CuO] 2 + ) [14] moieties to achieve the hydroxylation of aliphatic substrates (Figure 1, right).…”

“…[18][19][20] However, more and more biochemical evidence suggests that the oxidation mechanism proceeds by direct attack on the C À H bond by a copper superoxo intermediate [Cu II A C H T U N G T R E N N U N G (O 2 C À )] + . [12,[21][22][23][24][25][26] This possibility was recently explored by quantum chemistry. + adduct.…”

Copper(I) and Iron(II) Complexes of a Novel Tris(pyridyl)­ethane‐Derived N4 Ligand: Aspects of Redox Behaviour and Bioinorganic Physicochemistry

“…If the reaction is catalytic, the reactivity of [Cu I L(MeCN)]PF 6 (2) is similar to that of peptidylglycine α-hydroxylating monooxygenase (PHM, first reaction in Scheme 3) or copper-containing amine oxidases (second reaction in Scheme 3). [21] …”

Guanidine Metal Complexes for Bioinorganic Chemistry and Polymerisation Catalysis

“…12) [49,52]. The electronic and geometric properties of the superoxoCu(II) unit were characterised by isotopic probing [55], different spectroscopic techniques (i.e. magnetic circular dichroism and resonance Raman) and DFT calculations [56].…”