Synthesis and phosphate ester cleavage properties of copper(II) complexes of guanidinium-bridged bis(1,4,7-triazacyclononane) ligands

The synthesis and characterization of three new bis(1,4,7-triazacyclononane) ligands, L¹, L²and L³, featuring a bridging guanidinium group between two macrocyclic units, is reported. The corresponding binuclear copper(II) complexes have been studied as agents to accelerate the cleavage of P–O bonds within two model phosphodiesters, namely bis(p-nitrophenyl)phosphate (BNPP) and 2-hydroxypropyl-p-nitrophenylphosphate (HPNPP). The results of a comparative study of cleavage rates, using the mononuclear copper(II)–tacn complexes bearing single alkylguanidinium groups as a reference, revealed that the binuclear copper(II) complexes are generally less effective cleavage agents, which may be related to a tendency to form hydrolytically inactive hydroxo-bridged species at near-neutral pH and above. However, at pH 7, these complexes produced 4–18-fold increases in the rate of BNPP hydrolysis compared to the parent complex, [Cu(tacn)(OH₂)₂]²⁺. Likewise, at pH 6, the complexes cleaved HPNP 5–130-fold faster than [Cu(tacn)(OH₂)₂]²⁺, suggesting some degree of cooperative interplay between the two proximal copper(II) centers and the protonated guanidinium bridging group in promoting phosphodiester hydrolysis under these conditions.