New N4-Donor Ligands as Supramolecular Guests for DNA and RNA: Synthesis, Structural Characterization, In Silico, Spectrophotometric and Antimicrobial Studies

The present work reports the synthesis of new N4-donor compounds carrying p-xylyl spacers in their structure. Different Schiff base aliphatic N-donors were obtained synthetically and subsequently evaluated for their ability to interact with two models of nucleic acids: calf-thymus DNA (CT-DNA) and the RNA from yeast Saccharomyces cerevisiae (herein simply indicated as RNA). In more detail, by condensing p-xylylenediamine and a series of aldehydes, we obtained the following Schiff base ligands: 2-thiazolecarboxaldehyde (L1), pyridine-2-carboxaldehyde (L2), 5-methylisoxazole-3-carboxaldehyde (L3), 1-methyl-2-imidazolecarboxaldehyde (L4), and quinoline-2-carboxaldehyde (L5). The structural characterisation of the ligands L1-L5 (X-ray, H-1 NMR, C-13 NMR, elemental analysis) and of the coordination polymers {[CuL1]PF6}(n) (herein referred to as Polymer1) and {[AgL1]BF4}(n,) (herein referred to as Polymer2, X-ray, H-1 NMR, ESI-MS) is herein described in detail. The single crystal X-ray structures of complexes Polymer1 and Polymer2 were also investigated, leading to the description of one-dimensional coordination polymers. The spectroscopic and in silico evaluation of the most promising compounds as DNA and RNA binders, as well as the study of the influence of the 1D supramolecular polymers Polymer1 and Polymer2 on the proliferation of Escherichia coli bacteria, were performed in view of their nucleic acid-modulating and antimicrobial applications. Spectroscopic measurements (UV-Vis) combined with molecular docking calculations suggest that the thiazolecarboxaldehyde derivative L1 is able to bind CT-DNA with a mechanism different from intercalation involving the thiazole ring in the molecular recognition and shows a binding affinity with DNA higher than RNA. Finally, Polymer2 was shown to slow down the proliferation of bacteria much more effectively than the free Ag(I) salt.

Automated summary

This study reports the synthesis of new N4-donor compounds with p-xylyl spacers. Various Schiff base aliphatic N-donors were synthesized and evaluated for their interactions with calf-thymus DNA (CT-DNA) and yeast RNA. The structures of the ligands L1-L5 and coordination polymers Polymer1 and Polymer2 were characterized using X-ray, NMR, and elemental analysis. Spectroscopic analyses suggest that the thiazolecarboxaldehyde derivative L1 has a unique mechanism for binding CT-DNA and exhibits a higher affinity for DNA than RNA. Moreover, Polymer2 was found to be more effective than the free Ag(I) salt in inhibiting bacterial proliferation.