DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(II) terpyridine complexes

Puchta R, Arsenijević A, Bugarčić ŽD, Rilak A (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Dalton Transactions Royal Society of Chemistry

Book Volume: 45

Pages Range: 4633-4646

Journal Issue: 11

DOI: 10.1039/c5dt04132e

Abstract

In this study, two representatives of previously synthesized ruthenium(II) terpyridine complexes, i.e., [Ru(Cl-tpy)(en)Cl][Cl] (1) and [Ru(Cl-tpy)(dach)Cl][Cl] (2), were chosen and a detailed study of the kinetic parameters of their reactivity toward L-histidine (L-His), using the UV-Vis and 1H NMR techniques, was developed. The inner molecular rearrangement from N3-coordinated L-His to the N1 bound isomer, observable in the NMR data, was corroborated by DFT calculations favoring N1 coordination by nearly 4 kcal mol-1. These two ruthenium(II) terpyridine complexes were investigated for their interactions with DNA employing UV-Vis spectroscopy, DNA viscosity measurements and fluorescence quenching measurements. The high binding constants obtained in the DNA binding studies (Kb = 104-105 M-1) suggest a strong binding of the complexes to calf thymus (CT) DNA. Competitive studies with ethidium bromide (EB) showed that the complexes can displace DNA-bound EB, suggesting strong competition with EB (Ksv = 1.5-2.5 × 104 M-1). In fact, the results indicate that these complexes can bind to DNA covalently and non-covalently. In order to gain insight of the behavior of a neutral compound, besides the four previously synthesized cationic complexes [Ru(Cl-tpy)(en)Cl][Cl] (1), [Ru(Cl-tpy)(dach)Cl][Cl] (2), [Ru(Cl-tpy)(bpy)Cl][Cl] (3) and [Ru(tpy)Cl3] (P2), a new complex, [Ru(Cl-tpy)(pic)Cl] (4), was used in the biological studies. Their cytotoxicity was investigated against three different tumor cell lines, i.e., A549 (human lung carcinoma cell line), HCT116 (human colon carcinoma cell line), and CT26 (mouse colon carcinoma cell line), by the MTT assay. Complexes 1 and 2 showed higher activity than complexes 3, 4 and P2 against all the selected cell lines. The results on in vitro anticancer activity confirmed that only compounds that hydrolyze the monodentate ligand at a reasonable rate show moderate activity, provided that the chelate ligand is a hydrogen bond donor.

Authors with CRIS profile

Ralph Puchta Lehrstuhl für Anorganische und Metallorganische Chemie

Involved external institutions

University of Kragujevac RS Serbia (RS)

How to cite

APA:

Puchta, R., Arsenijević, A., Bugarčić, Ž.D., & Rilak, A. (2016). DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(II) terpyridine complexes. Dalton Transactions, 45(11), 4633-4646. https://doi.org/10.1039/c5dt04132e

MLA:

Puchta, Ralph, et al. "DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(II) terpyridine complexes." Dalton Transactions 45.11 (2016): 4633-4646.

BibTeX: Download