Impact of ligand steric hindrance on the phenoxazinone synthase-like reactivity and antibacterial activity of cobalt(iii) complexes of N2O donor ligands†

Abstract

In the present work, we have synthesized four new mono- and binuclear cobalt(III) complexes [Co(HL1)(L1)](NO₃)₂1, [Co(HL2)(L2)](NO₃)₂2, [Co(HL3)(L3)](NO₃)₂3 and [Co₂(L4)₂(NO₃)₂H₂O]·(NO₃)H₂O 4 composed of N₂O donor ligands (HL1 = 2-((pyridin-2-ylmethyl)amino)ethan-1-ol), HL2 = (1-((pyridin-2-ylmethyl)amino)propan-2-ol), HL3 = (3-((pyridin-2-ylmethyl)-amino)propan-1-ol) and HL4 = (2-methyl-2-((pyridin-2-ylmethyl)-amino)propan-1-ol)) and characterized them by various analytical methods. X-ray crystallographic analysis of complex cations [Co^III (HL1)(L1)]²⁺ and [Co^III (HL2)(L2)]²⁺ reveals that the Co(III) ion is in a distorted octahedral environment constructed by facial coordination of two equivalents of tridentate ligands (HL1/HL2). Interestingly, one equivalent of the ligand acts as an anionic donor, while neutral behaviour was noticed for the second equivalent. Complex 4 crystallises as a binuclear entity wherein the two cobalt centres communicate via a bis-μ-alkoxide bridge in the solid state. Both cobalt centres possess distorted octahedral geometry (Co1: the Co(III) ion is chelated to the N₄O₂ chromophore; Co2: the Co(II) ion is in an oxygen-rich O₆ environment). The ESI-MS profile of 4 in water shows that the mononuclear Co(III) species (m/z = 418.173) exists in the solution state. Furthermore, the spin and oxidation state of 1–4 in solution are assessed by the ¹H NMR spectroscopic data. All the complexes mimic the function of the phenoxazinone synthase enzyme with impressive turnover numbers (242.10–1424.95 h⁻¹) in water. From kinetic experiments, it is observed that complex 2 with a methyl substituted ligand moiety exhibits rapid PHS-like activity, and the reactivity of the catalysts follows the order: 2 > 3 > 4 > 1. The antibacterial activity of ligands (HL1–HL4), Co(NO₃)₂ and complexes 1–4 was tested individually against two Gram-positive and two Gram-negative bacteria and their minimum inhibitory concentration (MIC) was determined. Complexes 1–3 exhibited up to 92% inhibition of the growth of Klebsiella pneumoniae at a concentration of 100 μg mL⁻¹.