Organoplatinum(II) Complexes Self-Assemble and Recognize AT-Rich Duplex DNA Sequences

Giampaolo Barone, José Ruiz, Erin Wachter, Vanesa Fernández-Espín, Ana Zamora, María Vera, Enrique Ortega, David K. Heidary, Edith C. Glazer, Christoph Janiak, Venancio Rodríguez

Risultato della ricerca: Articlepeer review

1 Citazioni (Scopus)

Abstract

The specific recognition of AT-rich DNA sequences opens up the door to promising diagnostic and/or therapeutic strategies against gene-related diseases. Here, we demonstrate that amphiphilic PtII complexes of the type [Pt(dmba)(NΛN)]NO3 (dmba = N,N-dimethylbenzylamine-κN, κC; NΛN = dpq (3), dppz (4), and dppn (5)) recognize AT-rich oligonucleotides over other types of DNA, RNA, and model proteins. The crystal structure of 4 shows the presence of significant π-stacking interactions and a distorted coordination sphere of the d8 PtII atom. Complex 5, containing the largest π-conjugated ligand, forms supramolecular assemblies at high concentrations under aqueous environment. However, its aggregation can be promoted in the presence of DNA at concentrations as low as 10 μM in a process that "turns on"its excimer emission around 600 nm. Viscometry, gel electrophoresis, and theoretical calculations demonstrate that 5 binds to minor groove when self-assembled, while the monomers of 3 and 4 intercalate into the DNA. The complexes also inhibit cancer cell growth with low-micromolar IC50 values in 2D tissue culture and suppress tumor growth in 3D tumor spheroids with a multicellular resistance (MCR) index comparable to that of cisplatin.
Lingua originaleEnglish
pagine (da-a)2178-2187
Numero di pagine10
RivistaInorganic Chemistry
Volume60
Stato di pubblicazionePublished - 2021

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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