ABSTRACT The antimicrobial resistance crisis underscores the urgent need for innovative antibacterial agents. Silver‐based complexes represent a promising strategy due to their multi‐target mechanisms. In this work, a silver(I) complex with flexible acyclocytidine Ag 2 AcyC (NO 3 ) 2 was synthesized and structurally characterized. Single‐crystal X‐ray diffraction revealed a unique coordination pattern in which silver ions were bridged via N3–Ag–O2 linkages between cytosine bases, diverging from the conventional N3–Ag–N3 mode found in cytidine and 5‐methylcytidine complexes. Additional stabilization came from coordination with oxygen atoms (O4′, O5′) of the acyclic sugar moiety. This novel architecture resulted in a distinct electronic microenvironment around the silver centers. The complex demonstrated superior antibacterial activity against Escherichia coli and Staphylococcus aureus , showing lower MIC/MBC values and a higher inhibition rate—achieving 100% inhibition of E. coli at 40 μM (Ag + equivalent), significantly surpassing AgNO 3 . Crucially, it exhibited markedly reduced hemolytic toxicity and cytotoxicity. Mechanistic investigations confirmed that the complex enhances bacterial membrane disruption and reactive oxygen species (ROS) generation. This work not only presented a highly effective and biocompatible silver‐nucleoside antibacterial agent but also provided a promising strategy for developing novel silver‐based antibacterial agents.
Deng et al. (Fri,) studied this question.