Metal Complexes of a Multidentate Cyclophosphazene with Imidazole‐Containing Side Chains for Hydrolyses of Phosphoesters – Bimolecular vs. Intramolecular Dinuclear Pathway

A multidentate imidazole‐containing cyclophosphazene (Im 6 Cpz) ligand was synthesized and its metal complexes (M x Im 6 Cpz; M = Zn II , Cu II , Co II ; x = 1, 2, 3) were prepared and used as phosphoesterase models towards hydrolysis of the model substrates p ‐nitrophenylphosphate (NPP) and bis( p ‐nitrophenyl)phosphate (BNPP) in 75 % DMSO buffer solution at pH = 7–11 at 37 °C. The hydrolysis of BNPP by Cu 3 Im 6 Cpz exhibits enzyme‐like saturation kinetics with k cat = 1.4 × 10 –5 s –1 and k cat / K m = 0.0027 M –1 s –1 . The Cu II complex exhibits a tremendous selectivity toward NPP, showingnearly a stoichiometric binding with k cat = 6.8 × 10 –4 s –1 under saturation conditions and a significant second‐order rate constant k cat / K d = 136 M –1 s –1 , which is 5.0 × 10 4 times higher than that for BNPP hydrolysis. An intramolecular dinuclear pathway was revealed for the complexes Cu 2 Im 6 Cpz andCu 3 Im 6 Cpz; whereas an intermolecular dinuclear pathway was observed for CuIm 6 Cpz. Cu 3 Im 6 Cpz shows an order of magnitude higher activity than the simple Cu II complex of the untethered ligand N ‐methylimidazole, Cu(MeIm) 2 , suggesting a possible contribution from the proximity effect in the Im 6 Cpz complexes. The high catalytic specificity of Cu 3 Im 6 Cpz towards the phosphomonoester NPP suggests that it can serve as a good model system and a blueprint for further exploration of catalytic activity and specificity in phosphoester hydrolysis.