Metalloglycosidase Mimics: Oxidative Cleavage of Saccharides Promoted by Multinuclear Copper Complexes under Physiological Conditions.

Degradation of saccharides is relevant to the design of catalytic therapeutics, the production of biofuels, inhibition of biofilms, as well as other applications in chemical biology. Herein, we report the design of multinuclear Cu complexes that enable cleavage of saccharides under physiological conditions. Reactivity studies with para-nitrophenyl (pNP)-conjugated carbohydrates show that dinuclear Cu complexes exhibit a synergistic effect and promote faster and more robust cleavage of saccharide substrates, relative to the mononuclear Cu complex, while no further enhancement is observed for the tetranuclear Cu complex. The use of scavengers for reactive oxygen species confirms that saccharide cleavage is promoted by the formation of superoxide and hydroxyl radicals through CuII/I redox chemistry, similar to that observed for native copper-containing lytic polysaccharide monooxygenases (LMPOs). Differences in selectivity for di- and tetranuclear Cu complexes are modest. However, these are the first reported small multinuclear Cu complexes that show selectivity and reactivity against mono- and disaccharide substrates and form a basis for further development of metalloglycosidases for applications in chemical biology.

Spectroelectrochemical investigations of nickel cyclam indicate different reaction mechanisms for electrocatalytic CO2 and H+ reduction.

Rising levels of atmospheric carbon dioxide continue to motivate the development of catalysts that can efficiently convert CO2 to useful products in water without substantial amounts of H2 formed as a byproduct. In addition to synthetic efforts, mechanistic investigations on existing catalysts are necessary to understand the molecular factors contributing to activity and selectivity, which can guide rational improvements and increase catalyst robustness. [Ni(cyclam)]2+ (cyclam = 1,4,8,11-tetraazacyclotetradecane) is one such catalyst, known for decades to be capable of selective CO2 reduction to CO in water, but with little mechanistic information experimentally established or catalytic intermediates characterized. To better understand the mechanisms of aqueous H+ and CO2 reduction by [Ni(cyclam)]2+, spectroelectrochemical investigations were performed in conjunction with activity assays. Both large surface area glassy carbon and amorphous graphite rod working electrodes were tested, with the latter found to be significantly more active and selective for CO production. Optical, resonance Raman, and EPR spectroelectrochemical experiments on [Ni(cyclam)]2+ during catalysis under N2, CO2, and CO gases show the appearance of a single species, independent of electrode used. Identical signals are observed under oxidizing potentials. Spectroscopic and electrochemical analysis coupled with density functional theory calculations suggest that the signals observed originate from [Ni(cyclam)(H2PO4)]2+. The generation of a NiIII species under catalytic, reducing conditions suggests an ECCE mechanism for H+ reduction by [Ni(cyclam)]2+, which differs from the proton-coupled, ECEC pathway proposed for CO2 reduction. The divergent mechanisms seen for the two reactions may underlie the differential reactivity of [Ni(cyclam)]2+ towards each substrate, with implications for the design of increasingly selective molecular catalysts. This observation also highlights the substantial impact of buffer and electrode choice when characterizing and benchmarking the catalytic properties of new compounds.