Enantioselective DNA Threading Dynamics by Phenazine-Linked [Ru(phen)2dppz]2+ Dimers
Journal article, 2001

The interactions between the stereoisomers of the chiral bis-intercalator [mu -C4(cpdppz)(2)-(phen)(4)Ru-2](4+) and DNA reveal interesting dynamic discrimination properties. The two enantiomers Delta-Delta and Lambda-Lambda both form very strong complexes with calf thymus DNA with similar thermodynamic affinities. By contrast, they display considerable variations in their binding kinetics. The Delta-Delta enantiomer has higher affinity for calf thymus DNA than for [poly(dA-dT)](2), and the association kinetics of the dimer to DNA, as well as to polynucleotides, requires a multiexponential fitting function. The dissociation reaction, on the other hand, could be described by a single exponential for [poly(dA-dT)](2), whereas two exponentials were required for mixed-sequence DNA. To understand the key mechanistic steps of the reaction, the kinetics was studied at varied salt concentration for different choices of DNA and chirality of the threading complex. The enantiomers were found to have markedly different dissociation rates, the Lambda-Lambda enantiomer dissociating about an order of magnitude faster than the Delta-Delta enantiomer. Also. the salt dependence of the dissociation rate constants differed between the enantiomers, being stronger for the Lambda-Lambda enantiomer than for the Delta-Delta enantiomer. Since the dissociation reaction requires unthreading of bulky parts of the bis-intercalator through the DNA helix, a considerable conformational change of the DNA must be involved, possibly defining the rate-limiting step.

Author

Björn Önfelt

Department of Physical Chemistry

Per Lincoln

Department of Physical Chemistry

Bengt Nordén

Department of Physical Chemistry

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 124 16 3630-3637

Areas of Advance

Nanoscience and Nanotechnology (2010-2017)

Energy

Life Science Engineering (2010-2018)

Materials Science

Subject Categories

Physical Chemistry

Roots

Basic sciences

DOI

10.1021/ja003624d

More information

Created

10/7/2017