Copper-based bioinspired oxygenation and glyoxalase-like reactivity

Re-engineered, structurally abbreviated models of metalloenzymes may extend their biomimetic functionality to bioinspired reactivity. The oxygenation of external substrates, in particular, remains an important objective of biomimetic and bioinspired catalysis. We report that the reaction of [(Cu(I)TpCF3,CH3)2] with excess acetone in air produces [CuTpCF3,CH3)(lactate)] in over 95% yield at ambient conditions, without any noticeable ligand decomposition. This chemically unprecedented one-pot conversion of acetone to lactate occurs as a multistep process in the gluconeogenic pathway catalyzed by P450 isozyme 3a and Ni- or Zn-based glyoxalases. On the basis of the structure of the [CuTpCF3,CH3)(lactate)] product and oxygenation experiments using isotopically labeled acetone and water, an inner-sphere oxidation/isomerization mechanism is proposed.