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

Catalytic Cooperativity, Nuclearity, and O2/H2O2 Specificity of Multi‐Copper(II) Complexes of Cyclen‐Tethered Cyclotriphosphazene Ligands in Aqueous Media

“…However, the rate of oxidation of 6‐mM catechol by Cu 1 L1 is 6.8‐fold lower than that by Cu 2 L1 , suggesting that the mononuclear Cu 1 L1 complex does not contain the same structural motif as Cu 2 n L complexes for an effective catalysis that presumably follows a dinuclear pathway. Since the substrate‐bound intermediate [Cu L ]–S in Equation (1) is the catalytically active form, the mechanistically important stoichiometry of the intermediate can be determined by means of the “mechanistic Job plot”, [46b], to reveal the nuclearity during the catalysis. The oxidation of catechol by Cu 2 L1 , Cu 4 L2 , and Cu 6 L3 exhibit a maximum at X Cu L ≈ 0.5 (■, Figure ), 0.33 (○), and 0.25 (●) in their mechanistic Job plots, affording the Cu L /catechol ratios of 0.5:0.5, 0.33:0.67, and 0.25:0.75 (i.e., 1:1, 1:2, and 1:3), respectively.…”

“…The complexes herein possess all these properties. Moreover, the Cpz core is quite versatile for (a) systematic studies of the nature of the ligands (such as imidazole and cyclen‐containing arms herein), (b) assembling various di‐Cu centers (such as Cu 2 L1 , Cu 4 L2 , and Cu 6 L3 ), (c) building substrate specificity (described herein and the specific phosphomonoester recognition and hydrolysis), (d) rendering catalytic cooperativity in oxidation (Figure A) and hydrolysis, (e) exhibiting more specific oxidation reactions by O 2 than by H 2 O 2 (Table ), (f) possibly building a potential substrate recognition site in the proximity of the metal center, and (g) exploration of other activities by various metal complexes of Cpz‐containing ligands in the future.…”

“…The stoichiometry of a metal complex M–L n in the equilibrium M + n L ⇄ M–L n can be determined by means of the Job plot, wherein the total concentration [M] + [L] is kept constant while the metal‐to‐ligand ratio is varied and the optical density of the complex is monitored . Likewise, the presence of the pre‐equilibrium Cu L + S ⇄ S–Cu L in the catalysis of catechol oxidation allows the use of the “mechanistic Job plot, ” to determine the stoichiometry of the substrate‐bound complex S–Cu L in the reaction mechanism by monitoring the reaction rate that directly reflects the concentration of the intermediate (i.e., rate = k cat [S–Cu L ]), analogous to the optical density of the complex in the conventional Job plot. In this case, the total concentration ([Cu L ] + [S]) is kept constant while the ratio [Cu L ]/[S] varies and the oxidation rate of the substrate S is monitored.…”

“…The complexes of Cpz‐containing ligands with tethered imidazole or other N ‐heterocyclic groups exhibit activities toward cleavage of plasmid DNA under physiological conditions . The Cu complexes of the imidazole derivatives exhibit significantly more effective and specific hydrolytic activity toward a phosphomonoester ( K d = 5 µ m ) than a phosphodiester, showing significant cooperativity with θ = 1.5 for a maximum of 2 for two potential binding sites and following a dinuclear mechanism that mimics alkaline phosphatase …”

Synthesis and Characterization of Side Group-Modified Tetradentate Cyclotriphosphazene Derivatives

“…Different side-group structures affect the chemical and physical properties of ring systems and high polymers based on a phosphazene skeleton. [4][5][6][7][8][9][10][11] Recently, we reported some polydentate cyclotriphosphazene ligands, [12][13][14] which showed good nuclease activity with hydrolytic cleavage mechanism. To obtain more insight into the selective recognition and efficient cleavage of DNA by different metal complexes of cyclotriphosphazene, in this work we synthesized a series of novel tetradentate cyclotriphosphazene derivatives in good yield via convenient reactions.…”