Impact of the zinc complexation of polytopic polyaza ligands on the interaction with double and single stranded DNA/RNA and antimicrobial activity

Metal complexes have gained a huge interest in the biomedical research in the last decade because of the access to unexplored chemical space with regards to organic molecules and to present additional functionalities to act simultaneously as diagnostic and therapeutic agents. Herein, we evaluated th...

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Published in:Dalton transactions : an international journal of inorganic chemistry 2023-05, Vol.52 (17), p.5478-5485
Main Authors: González-García, Jorge, Galiana, Carolina, Dea-Ayuela, M. Auxiliadora, Radi Stojkovi, Marijana, López-Molina, Sonia, Galiana-Roselló, Cristina, Blasco, Salvador, Piantanida, Ivo, García-España, Enrique
Format: Article
Language:English
Subjects:
Anti-Infective Agents - chemistry
Antiinfectives and antibacterials
Antimicrobial agents
Binding
Coordination Complexes - chemistry
Coordination compounds
Deoxyribonucleic acid
Dichroism
DNA
DNA - chemistry
DNA, Single-Stranded
E coli
Escherichia coli
Fluorimetry
Gene sequencing
Ligands
Organic chemistry
Pharmacology
Reagents
Ribonucleic acid
RNA
RNA - chemistry
Staphylococcus aureus
Thermal denaturation
Zinc
Zinc - chemistry
Zinc compounds
Zinc coordination
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Summary:Metal complexes have gained a huge interest in the biomedical research in the last decade because of the access to unexplored chemical space with regards to organic molecules and to present additional functionalities to act simultaneously as diagnostic and therapeutic agents. Herein, we evaluated the interaction of two polytopic polyaza ligands and their zinc complexes with DNA and RNA by UV thermal denaturation, fluorescence and circular dichroism spectroscopic assays. The zinc coordination was investigated by X-ray diffraction and afforded the structure of the binuclear zinc complex of PYPOD . Thermal denaturation of DNA and RNA and fluorimetry analysis revealed preferential binding of the zinc- PHENPOD complexes towards GC-containing DNA in contrast to the free ligands. On the other hand, PYPOD metal complexes, compared to the free ligand, stabilized AT-based DNA (B-form) better than AU-RNA (A-form). With regards to single stranded RNA, the binuclear complex of PHENPOD and the free ligand can efficiently identify polyadenylic acid (poly A) among other RNA sequences by circular dichroism spectroscopy. The antimicrobial activity in S. aureus and E. coli bacteria showed the highest activity for the free ligands and their trinuclear zinc complexes. This work can provide valuable insights into the impact of the nuclearity of polytopic polyaza ligands in the binding to DNA/RNA and the antimicrobial effect. Two polytopic ligands and their zinc complexes show a high interaction with DNA/RNA and different recognition abilities of the nucleic acids depending on the base composition. The antimicrobial activity is higher for the free ligands.
ISSN:1477-9226
1477-9234
DOI:10.1039/d3dt00395g