Phenoxazinone Synthase-Like Catalytic Activity of Bi- and Trinuclear Copper(II) Complexes with 2-Benzylethanolamine: Experimental and Theoretical Investigations

The self-assembly reaction of 2-benzylaminoethanol (Hbae) with CuCl₂ or Cu(NO₃)₂ leads to the formation of binuclear [Cu₂(bae)₂(Cl)₂] (1) and [Cu₂(Hbae)₂(bae)₂](NO₃)₂ (2) complexes, while the trinuclear [Cu₃(Hbae)₂(bae)₂(dmba)₂](NO₃)₂ (3) compound was obtained using the auxiliar bulky substituted 2,2-dimethylbutyric acid (Hdmba). Crystallographic studies reveal the molecular structures of 1 and 2 based on the similar {Cu₂(μ-O)₂} core, while the structure of 3 features the {Cu₃(μ-O)₂} core with consecutive arranement of the metal centres, supported by the additional carboxylate bridges. The strong intermolecular hydrogen bonds join the molecular structures into 1D (for 1 and 3) or 2D (for 2) architectures. All three compounds act as catalysts for the aerobic oxidation of 2-aminophenol to the phenoxazinone chromophore (phenoxazinone synthase-like activity) with the maximum reaction rates up to 2.3×10⁻⁸ M s⁻¹. The substrate scope involves methyl-, nitro- and chloro-substituted 2-aminophenols, disclosing the negligible activity of nitro-derivatives, while the 6-amino-m-cresol substrate shows the highest activity with the initial reaction rate of 5.8×10⁻⁸ M s⁻¹. The mechanism of the rate-limiting reaction step (copper-catalysed formation of 2-aminophenoxyl radicals) was investigated at the DFT level. The combined DFT and CASSCF studies of the copper superoxo Cu^II-OO⋅ radical species as possible unconventional reaction intermediates resulted in a rational mechanism of H-atom abstraction, where the activation energies follow the experimental reactivity of substituted 2-aminophenols. The TDDFT and STEOM-DLPNO-CCSD theoretical calculations of the absorption spectra of substrates, phenoxazinone chromophores and putative polynuclear species containing 2-aminophenoxo ligand are reported.