A Stereoselective Tyrosinase Model Compound Derived from an m-Xylyl- l -histidine Ligand

The aim of mimicking enzyme activity
represents an important motivation for the development of
new catalysts. A challenging objective is the development of
chiral complexes for bioinspired enantioselective oxidation
reactions. Herein, we report a new chiral dinuclear copper(II)
complex based on a m-xylyl-bis(histidine) ligand (mXHI) as a
biomimetic catalyst for tyrosinase and catechol oxidase. The
new ligand improves a previous system also containing two
tridentate N3 units derived from L-histidine that were
connected by a short, rigid ethanediamine bridge. In mXHI
the bridge is provided by the more extended m-xylyl moiety. The dicopper(II) complex [Cu2(mXHI)]4+ was studied as a
catalyst for stereoselective oxidations of enantiomeric couples of chiral catechols of biological interest (L/D-dopa, L/D-dopa
methyl ester, and (R/S)-norepinephrine), showing excellent discrimination capability, particularly for the methyl esters of dopa
enantiomers. The catechol oxidation was studied in acetate buffer as slightly acidic medium, and a role of acetate as bridging
ligand between the two coppers, preorganizing the dinuclear center in a more catalytic efficient structure, could be established.
The oxidation of β-naphthol and 3,5-ditertbutylphenol was studied as a model monophenolase reaction. The oxidation proceeds
stoichiometrically, and the partial incorporation of 18O into β-naphthol when the reaction was performed using 18O2 suggests
the existence of two competitive reaction pathways, a genuine monooxygenase mechanism and a radical pathway. However, the
more challenging reaction on derivatives of L-/D-tyrosine did not lead to the desired monooxygenase product but only to
products of radical oxidation. Complex [Cu2(mXHI)]4+ was also used for the catalytic sulfoxidation of thioanisole in the
presence of hydroxylamine as cosubstrate, in a preliminary attempt to model the reaction of external monooxygenases. The
reaction proceeds with 25 turnovers, but the enantiomeric excess of sulfoxide was modest.