A nucleotide-copper(II) complex possessing a monooxygenase-like catalytic function.

The de novo design of artificial biocatalysts with enzyme-like active sites and catalytic functions has long been an attractive yet challenging goal. In this study, we present a nucleotide-Cu 2+ complex, synthesized through a one-pot approach, capable of catalyzing ortho -hydroxylation reactions resembling those of minimalist monooxygenases. Both experimental and theoretical findings demonstrate that the catalyst, in which Cu 2+ coordinates with both the nucleobase and phosphate moieties, forms a ternary-complex intermediate with H 2 O 2 and tyramine substrates through multiple weak interactions. The subsequent electron transfer and hydrogen (or proton) transfer steps lead to the ortho -hydroxylation of tyramine, where the single copper center exhibits a similar function to natural dicopper sites. Moreover, Cu 2+ bound to nucleotides or oligonucleotides exhibits thermophilic catalytic properties within the temperature range of 25 °C to 75 °C, while native enzymes are fully deactivated above 35 °C. This study may provide insights for the future design of oxidase-mimetic catalysts and serve as a guide for the design of primitive metallocentre-dependent enzymes.