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

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish
Pages (from-to)2178-2187
Number of pages10
JournalInorganic Chemistry
Volume60
Issue number4
DOIs
StatePublished - Feb 15 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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