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The Thermodynamic Effects of Ligand Structure on the Molecular Recognition of Mono‐ and Biruthenium Polypyridyl Complexes with G‐Quadruplex DNA
Author(s) -
Mikek Clinton G.,
Machha Venkata R.,
White Jake C.,
Martin Logan R.,
West Savannah J.,
Butrin Arseniy,
Shumaker Carmen,
Gwin J. Cole,
Alatrash Nagham,
MacDonnell Frederick M.,
Lewis Edwin A.
Publication year - 2017
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201700789
Subject(s) - chemistry , isothermal titration calorimetry , circular dichroism , crystallography , ruthenium , stereochemistry , g quadruplex , dna , titration , ligand (biochemistry) , catalysis , biochemistry , receptor
Isothermal titration calorimetry (ITC) and circular dichroism (CD) were used to study the thermodynamics of RPC · G‐quadruplex DNA (G4) complex formation. The ruthenium polypyridyl complexes (RPCs) were [Ru(phen) 3 ] 2+ ( 1 2+ ), [Ru(phen) 2 (dppz)] 2+ ( 2 2+ ), [Ru(phen) 2 (tatpp)] 2+ ( 3 2+ ), and [Ru(phen) 2 (tatpp)(phen) 2 Ru] 4+ ( 4 4+ ), and target DNAs were c‐MYC NHE‐III 1 promoter sequence mutants forming 1‐2‐1 and 1‐6‐1 G‐quadruplexes. Formation of the 2:1 RPC · G4 complexes is characterized by entropy driven RPC binding to the top and bottom of G‐tetrad faces. 1 2+ appears to bind very weakly or not at all to G4 DNA. 2 2+ having a dipyridophenazine group to stack on the top and bottom of the G4 core, exhibits an average K a = 6.7 × 10 4 m –1 . 3 2+ , with a larger G4 interactive tetraazatetrapyridopentacene group, binds with significantly higher affinity, K a = 1.1 × 10 6 m –1 . 2 2+ and 3 2+ appear to bind independently of G4 folding topology and RPC conformation. The thermograms for the titration of G4 DNA with rac ‐4 4+ are characterized by two binding modes exhibiting higher and lower affinity ( K a,1 = 3.6 × 10 7 m –1 and K a,2 = 3.2 × 10 5 m –1 ). The two binding modes are attributed to preferential binding of one of the 4 4+ enantiomers (e.g. ΛΛ) over the other isomers (e.g. ΔΔ or ΔΛ). Tighter binding of the preferred 4 4+ enantiomer, in comparison to 3 2+ , is due to additional favorable entropy for locating a second [(phen) 2 Ru–] 2+ moiety in a G4 groove. Weaker binding of the disfavored 4 4+ isomers must be due to a poorer fit of these isomers with the G4 faces.