Zn(ii)/Ag(i) bi-heterometallic-based assemblies with unexpectedly high catalytic activity for the hydrolysis of phosphodiesters

Abstract

Almost all reported artificial phosphodiesterases with high catalytic efficiency are based on binuclear homometallic models, typically involving two Zn²⁺ ions or two adjacent Zn²⁺ centers forming a catalytic pocket within multivalent assemblies (e.g., Au nanoparticles). However, bi-heterometallic artificial phosphodiesterases remain largely unexplored, representing significant research potential in this field. In this work, we synthesized a series of TACN-based derivatives, in which a 1,4,7-triazacyclononane (TACN) group was linked to a succinimide moiety (containing an imide unit) via an alkyl chain of varying lengths (C_n, n = 7, 14, and 18). This connection was achieved through a thiol–alkene click reaction, creating TACN derivatives denoted as TACN-C_n-S-succinimide, featuring a terminal TACN and a terminal imide group. Upon the addition of equimolar Zn²⁺ and Ag⁺ ions to aqueous solutions of TACN-C_n-S-succinimide, Zn²⁺·TACN-C_n-S-succinimide·Ag⁺ assemblies were formed through selective coordination: Zn²⁺ binding to TACN and Ag⁺ associating with the succinimide moiety due to their distinct coordination preferences. When the concentration of Zn²⁺·TACN-C_n-S-succinimide·Ag⁺ reached the critical aggregation concentration (CAC), assemblies were generated to offer multivalent systems, beneficial for biomimetic catalysis. Notably, unlike the relatively low catalytic activities observed in the di-homometallic Zn²⁺/Zn²⁺ and Ag⁺/Ag⁺ systems, the heterometallic Zn²⁺/Ag⁺ assemblies, specifically Zn²⁺·TACN-C₁₄-S-succinimide·Ag⁺ and Zn²⁺·TACN-C₁₈-S-succinimide·Ag⁺, exhibited significantly enhanced catalytic activity in the hydrolysis of the RNA model substrate 2-hydroxypropyl-p-nitrophenyl phosphate (HPNP). This remarkable catalytic performance is unexpected. The pronounced difference in catalytic efficiency between the Zn²⁺/Ag⁺ system and its di-homometallic counterparts is likely attributed to the contrasting Lewis acid softness between Ag⁺ and Zn²⁺. This hypothesis is supported by density functional theory (DFT) calculations, which reveal a reduced energy barrier between the second intermediate and transition state in the Zn²⁺/Ag⁺ system.