A Supramolecular Interaction of a Ruthenium Complex With Calf-Thymus DNA: A Ligand Binding Approach by NMR Spectroscopy

Author(s)

Crizostomo Kock, Flavio Vinicius ; Costa, Analu Rocha ; de Oliveira, Katia Mara ; Batista, Alzir Azevedo ; Ferreira, Antonio Gilberto ; Venancio, Tiago

• Document type: Journal article
• Source: RONTIERS IN CHEMISTR; v. 7, p. 10-pg., 2019-11-08.

Abstract

Lawsone itself exhibits interesting biological activities, and its complexation with a metal center can improve the potency. In this context a cytotoxic Ru-complex, [Ru(law)(dppb)(bipy)] (law = lawsone, dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2 '-bipyridine), named as CBLAU, was prepared as reported. In this work, NMR binding-target studies were performed to bring to light the most accessible interaction sites of this Ru-complex toward Calf-Thymus DNA (CT-DNA, used as a model), in a similar approach used for other metallic complexes with anti-cancer activity, such as cisplatin and carboplatin. Advanced and robust NMR binding-target studies, among them Saturation Transfer Difference (STD)-NMR and longitudinal relaxometry (T-1), were explored. The H-1 and P-31 -NMR data indicate that the structure of Ru-complex remains preserved in the presence of CT-DNA, and some linewidth broadening is also observed for all the signals, pointing out some interaction. Looking at the binding efficiency, the T-1 values are highly influenced by the formation of the CBLAU-DNA adduct, decreasing from 11.4 s (without DNA) to 1.4 s (with DNA), where the difference is bigger for the lawsone protons. Besides, the STD-NMR titration experiments revealed a stronger interaction (K-D = 5.9 mM) for CBLAU-DNA in comparison to non-complexed lawsone-DNA (K-D = 34.0 mM). The epitope map, obtained by STD-NMR, shows that aromatic protons from the complexed lawsone exhibits higher saturation transfer, in comparison to other Ru-ligands (DPPB and bipy), suggesting the supramolecular contact with CT-DNA takes place by the lawsone face of the Ru-complex, possibly by a spatial pi-pi stacking involving pi-bonds on nucleic acids segments of the DNA chain and the naphthoquinone group. (AU)

• FAPESP's process: 18/19342-2 - Metal complexes with dirivative ligands of lawsone and acylthioureas, with anticancer potential activities: study in vitro and in vivo.
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/16040-5 - Biorational control of Pest-Insect
• Grantee: Flavio Vinicius Crizostomo Kock
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/09145-5 - Characterization of supramolecular complexes by solution and solid state high resolution Nuclear Magnetic Resonance
• Grantee: Tiago Venancio
• Support Opportunities: Regular Research Grants