Substituent effects in picolinic acid-derived silver(I) and zinc(II) complexes: Structure, stability, DNA interactions and therapeutic potential.

3-substituted derivatives of picolinic acid, 3-methylpicolinic acid (3-MePicH) and 3-hydroxypicolinic acid (3-OHPicH), were used to investigate their complex-forming, structural, spectral, and thermal properties toward biologically active silver(I) and zinc(II) ions. In the case of the 3-MePicH ligand, potentiometric and 1H NMR titrations confirmed the formation of complex species [Ag(3-MePic)], [Zn(3-MePic)]+, and [Zn(3-MePic)₂]. In contrast, the 3-OHPicH ligand was incorporated into the coordination sphere of the Ag(I) and Zn(II) central atoms only in the form of protonated complex species. Under ecofriendly conditions, the complexes were isolated in solid state; their IR, NMR, thermal analyses, molar conductivity and for the zinc(II) complex with the 3-methylpicolinate ligand also single-crystal analysis confirmed their composition: [Ag(3-MePic)]·0.5H₂O (Ag3-MePic), [Zn(3-MePic)₂(H₂O)] (Zn3-MePic), [Ag(3-OHPic)] (Ag3-OHPic), [Zn(3-OHPic)₂(H₂O)₂] (Zn3-OHPic). The stability of the investigated complexes in biologically relevant solvents made it possible to evaluate their antimicrobial and anticancer activity. Compared with AgPic (the analogous silver(I) complex with picolinic acid), a more significant antibacterial and antifungal activity for Ag3-OHPic was confirmed, as well as higher cytotoxicity for both pyridine-substituted silver(I) complexes against A549 (36.3 μM) and Jurkat (37.8 μM) cells. The interactions of the silver(I) complexes with human serum albumin and calf thymus DNA were also investigated, followed by an evaluation of their potential inhibitory effects on human topoisomerases I and II. Among the tested compounds, Ag3-MePic exhibited the most pronounced inhibitory activity against Topoisomerase II at a concentration of 0.5 μM.