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Polypyridyl‐Based Copper Phenanthrene Complexes: A New Type of Stabilized Artificial Chemical Nuclease
Author(s) -
Zuin Fantoni Nicoló,
Molphy Zara,
Slator Creina,
Menounou Georgia,
Toniolo Gianluca,
Mitrikas George,
McKee Vickie,
Chatgilialoglu Chryssostomos,
Kellett Andrew
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201804084
Subject(s) - chemistry , nuclease , electron paramagnetic resonance , copper , stereochemistry , phenazine , bipyridine , dna , combinatorial chemistry , crystallography , organic chemistry , nuclear magnetic resonance , biochemistry , crystal structure , physics
The building of robust and versatile inorganic scaffolds with artificial metallo‐nuclease (AMN) activity is an important goal for bioinorganic, biotechnology, and metallodrug research fields. Here, a new type of AMN combining a tris‐(2‐pyridylmethyl)amine (TPMA) scaffold with the copper(II) N , N′ ‐phenanthrene chemical nuclease core is reported. In designing these complexes, the stabilization and flexibility of TPMA together with the prominent chemical nuclease activity of copper 1,10‐phenanthroline (Phen) were targeted. A second aspect was the opportunity to introduce designer phenazine DNA intercalators (e.g., dipyridophenazine; DPPZ) for improved DNA recognition. Five compounds of formula [Cu(TPMA)( N , N ′)] 2+ (where N , N ′ is 2,2‐bipyridine (Bipy), Phen, 1,10‐phenanthroline‐5,6‐dione (PD), dipyridoquinoxaline (DPQ), or dipyridophenazine (DPPZ)) were developed and characterized by X‐ray crystallography. Solution stabilities were studied by continuous‐wave EPR (cw‐EPR), hyperfine sublevel correlation (HYSCORE), and Davies electron–nuclear double resonance (ENDOR) spectroscopies, which demonstrated preferred geometries in which phenanthrene ligands were coordinated to the copper(II) TPMA core. Complexes with Phen, DPQ, and DPPZ ligands possessed enhanced DNA binding activity, with DPQ and DPPZ compounds showing excellent intercalative effects. These complexes are effective AMNs and analysis with spin‐trapping scavengers of reactive oxygen species and DNA repair enzymes with glycosylase/endonuclease activity demonstrated a distinctive DNA oxidation activity compared to classical Sigman‐ and Fenton‐type reagents.