Synthesis and DNA cleavage studies of rationally designed metallopeptides from N-salicyl-AA-picolamide (SAP) and Cu(ii) ions†

Abstract

Salicylic acid derivatives are key components of many bioactive natural products. Recently developed salicyl-picolamine conjugated peptides, termed N-salicyl-AA-picolamides (SAPs), have exhibited potent anti-quorum sensing activities. This study details the synthesis and structural characterization of novel SAP–Cu(II) complex crystals, exhibiting an unusual distorted square planar and square pyramidal geometry. Notably, the inter-copper distances within these complexes range between 3.4 Å and 3.5 Å, which are shorter than those observed in oxyhemocyanin. The SAP–Cu(II) complexes demonstrate significant catalytic redox potential, enhancing their utility in the development of catalytic metallodrugs that operate via reactive oxygen species (ROS)-mediated oxidation of biomolecules. Furthermore, these complexes have been shown to efficiently cleave supercoiled plasmid DNA when combined with ascorbic acid and H₂O₂. This suggests that SAP peptides are promising candidates for engineering Cu(II) chelating ligands and DNA cleavage agents through the incorporation of diverse amino acids.