Stereospecific DNA binding of luminescent atropisomeric viologens.
Binding to B-DNA of one enantiomer of dq3pyp, --a member of a novel family of intercalating luminescent viologens derived from N,N'-dialkyl-6-(2-pyridyl)phenanthridine, in which dialkyl is -(CH2)2- (dq2pyp), -(CH2)3- (dq3pyp), or (-CH3)2 (Me2pyp)--, is strongly favored compared to its estable atropisomer. Evidence of the stereospecific interaction has been gained by resolution of a rac-dq3pyp mixture upon dialysis in the presence of DNA, monitored by circular dichroism. Molecular modeling suggests that the S enantiomer of both dq3pyp and dq2pyp is the one preferred for the binding. No similar resolution has been achieved with rac-dq2pyp due to the lower barrier to interconversion of its atropisomers, as shown by 1H-NMR. The identical binding energy of the two modeled diastereoisomeric Me2pyp-DNA complexes discard enantiospecific interaction of this drug. Affinity chromatography on DNA-cellulose allows isolation of the pure enantiomers of dq3pyp.
Bárcena
M
M
Department of Biochemistry, Faculty of Chemistry, Complutense University of Madrid, Spain.
Colmenarejo
G
G
Gutiérrez-Alonso
M C
MC
Montero
F
F
Orellana
G
G
D002942:Circular Dichroism; D003196:Computer Graphics; D004247:DNA / Q000737:chemistry*; D007536:Isomerism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship; D014755:Viologens / Q000737:chemistry*
D014755:Viologens; D004247:DNA