Copper(ii) complexes of dipica and its derivatives as biomimetic models for phenoxazinone synthase: probing the effect of central N-cycloalkyl rings on reactivity

Abstract

A series of copper(II) complexes 1–4 of the type [Cu(L1–L4)Cl₂] incorporating tridentate 3N donor ligands L1–L4 were synthesized and evaluated as biomimetic models for phenoxazinone synthase enzyme (PHS). The ligands employed are bis(pyridin-2-ylmethyl)amine (L1, dipica), N,N-bis(pyridin-2-ylmethyl)cyclopropanamine (L2), N,N-bis(pyridin-2-ylmethyl)cyclopentanamine (L3), and N,N-bis(pyridin-2-ylmethyl)cycloheptanamine (L4). All the ligands and their copper(II) complexes were characterized by various spectroscopic and analytical methods. Out of the four complexes, complexes 2–4 are isostructural and exhibit a trigonal bipyramidal distorted square-based pyramidal geometry (TBDSBP) (τ₅: 2a, 0.25, 2b, 0.296; 3, 0.399; 4, 0.209), encompassing a CuN₃Cl₂ chromophore around the copper(II) centre, as revealed by single-crystal X-ray diffraction analyses. The solution-state EPR studies of complexes showed g_‖ = 2.23–2.25 and A_‖ = 180–200 × 10⁻⁴ cm⁻¹ values, and absorption spectral analysis (675–700 nm) clearly deduced the presence of square-based geometry in the solution state. All the complexes exhibit quasireversible Cu(II)/Cu(I) redox behavior and the E_1/2 value of 3 (−0.143 V) is less negative than that of 1 (−0.224 V), 2 (−0.156 V) and 4 (−0.172 V) in aqueous solutions. Complexes 1–4 serve as the small-molecule models of PHS by catalyzing the conversion of 2-aminophenol into phenoxazinone in an aqueous medium and display significant k_cat values of 1810–4210 h⁻¹ in H₂O. Interestingly, the turnover number of 3 is significantly higher than that of 1, 2 and 4 in an aqueous solution. Indeed, complex 3, appended with the conformationally less flexible and sterically demanding cyclopentyl group, forces the basal plane donor atoms to move away from the central copper(II) ion, shows enhanced Lewis acidity of the Cu(II) ion, which, in turn, promotes the Cu^II/Cu^I redox process during the catalytic cycle, and brings a higher turn-over number (4210 h⁻¹) in PHS-mimicking catalysis.