Low Temperature Syntheses and Reactivity of Cu2O2 Active-Site Models

• Published in: Accounts of chemical research 2015-08, Vol.48 (8), p.2424-2433
• Main Authors: Citek, Cooper, Herres-Pawlis, Sonja, Stack, T. Daniel P
• Format: Article
• Language: English
• ISSN: 0001-4842; 1520-4898
• DOI: 10.1021/acs.accounts.5b00220

Nature’s facility with dioxygen outmatches modern chemistry in the oxidation and oxygenation of materials and substrates for biosynthesis and cellular metabolism. The Earth’s most abundant naturally occurring oxidant isfranklypoorly understood and controlled, and thus underused. Copper-based enzyme metallocofactors are ubiquitous to the efficient consumption of dioxygen by all domains of life. Over the last several decades, we have joined many research groups in the study of copper- and dioxygen-dependent enzymes through close investigation of synthetically derived, small-molecule active-site analogs. Simple copper-dioxygen clusters bearing structural and spectroscopic similarity to dioxygen-activating enzymes can be probed for their fundamental geometrical, electronic, and reactive properties using the tools available to inorganic and synthetic chemistry. Our exploration of the copper-dioxygen arena has sustained product evaluation of the key dynamics and reactivity of binuclear Cu2O2 compounds. Almost exclusively operating at low temperatures, from −78 °C to solution characterization even at −125 °C, we have identified numerous compounds supported by simple and easily accessed, low molecular weight ligandschiefly families of bidentate diamine chelates. We have found that by stripping away complexity in comparison to extended protein tertiary structures or sophisticated, multinucleating architectures, we can experimentally manipulate activated compounds and open pathways of reactivity toward exogenous substrates that both inform on and extend fundamental mechanisms of oxygenase enzymes. Our recent successes have advanced understanding of the tyrosinase enzyme, and related hemocyanin and NspF, and the copper membrane monooxygenases, specifically particulate methane monooxygenase (pMMO) and ammonia monooxygenase (AMO). Tyrosinase, ubiquitously distributed throughout life, is fundamental to the copper-based oxidation of phenols and the production of chromophores by dedicated biosynthesis or incidental oxidative browning. The copper membrane monooxygenases are comparatively new entrants to the copper-dioxygen field. While pMMO mediates the synthetically tantalizing transformation of methane to methanol, AMO catalyzes the first metabolic step in deriving chemical energy from ammoniaa reaction massively represented on a global scale and a critical component of chemical homeostasis on Earth. In this Account, we begin by introduction of the synthetic copper-d