Canonical DNA minor groove insertion of bisbenzamidine-Ru(ii) complexes with chiral selectivity

resumo

We report the first Ru(ii) coordination compounds that interact with DNA through a canonical minor groove insertion mode and with selectivity for A/T rich sites. This was made possible by integrating a bis-benzamidine minor groove DNA-binding agent with a ruthenium(ii) complex. Importantly, one of the enantiomers (Delta-[Ru(bpy)(2)b4bpy](2+), Delta-4Ru) shows a considerably higher DNA affinity than the parent organic ligand and the other enantiomer, particularly for the AATT sequence, while the other enantiomer preferentially targets long AAATTT sites with overall lower affinity. Finally, we demonstrate that the photophysical properties of these new binders can be exploited for DNA cleavage using visible light.

palavras-chave

MOLECULAR LIGHT SWITCH; METAL-COMPLEXES; RUTHENIUM(II) COMPLEXES; POLYPYRIDYL COMPLEXES; BINDING GEOMETRIES; LINEAR DICHROISM; BINDERS; LIGAND; PHOTOOXIDATION; INTERCALATION

categoria

Chemistry

autores

Sanchez, MI; Rama, G; Calo-Lapido, R; Ucar, K; Lincoln, P; Lopez, MV; Melle-Franco, M; Mascarenas, JL; Vazquez, ME

nossos autores

agradecimentos

Financial support from the Spanish grants CTQ2015-70698-R, SAF2016-76689-R and Orfeo-cinqa network CTQ2016-81797-REDC; the Ministerio de Ciencia, Innovacion y Universidades of Spain, RTI2018-099877-B-I00; the Xunta de Galicia (2015-CP082, ED431C 2017/19, Centro singular de investigacion de Galicia accreditation 2016-2019, ED431G/09), the European Union (European Regional Development Fund - ERDF), and the European Research Council (Advanced Grant No. 340055) are gratefully acknowledged. We also acknowledge the support from the Portuguese Foundation for Science and Technology, FCT, (IF/00894/2015) and CICECO - Aveiro Institute of Materials, FCT Ref. UID/CTM/50011/2019, financed by national funds through the FCT/MCTES. M. E. V. also acknowledges the support of the Fundacion Asociacion Espanola Contra el Cancer (AECC) (IDEAS197VAZQ grant). We also thank A. Arda and J. Jimenez-Barbero (CIC bioGUNE) for carrying out the preliminary spectroscopic characterization.

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