Insights into Structure and Biological Activity of Copper(II) and Zinc(II) Complexes with Triazolopyrimidine Ligands

In an attempt to increase the biological activity of the 1,2,4-triazolo[1,5-a]pyrimidine scaffold through complexation with essential metal ions, the complexes trans-[Cu(mptp)(2)Cl-2] (1), [Zn(mptp)Cl-2(DMSO)] (2) (mptp: 5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine), [Cu-2(dmtp)(4)Cl-4]center dot 2H(2)O (3) and [Zn(dmtp)(2)Cl-2] (4) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized as new antiproliferative and antimicrobial species. Both complexes (1) and (2) crystallize in the P2(1)/n monoclinic space group, with the tetrahedral surroundings generating a square-planar stereochemistry in the Cu(II) complex and a tetrahedral stereochemistry in the Zn(II) species. The mononuclear units are interconnected in a supramolecular network through pi-pi interactions between the pyrimidine moiety and the phenyl ring in (1) while supramolecular chains resulting from C-H center dot center dot center dot pi interactions were observed in (2). All complexes exhibit an antiproliferative effect against B16 tumor cells and improved antibacterial and antifungal activities compared to the free ligands. Complex (3) displays the best antimicrobial activity against all four tested strains, both in the planktonic and biofilm-embedded states, which can be correlated to its stronger DNA-binding and nuclease-activity traits.

Automated summary

In an attempt to enhance the biological activity of the 1,2,4-triazolo[1,5-a]pyrimidine scaffold, complexes were synthesized and characterized as new antiproliferative and antimicrobial species. These complexes showed improved activities compared to the free ligands.