Dinuclear ruthenium(ii) complexes with flexible bridges as non-duplex DNA binding agents.
The stereoisomers of a series of dinuclear ruthenium(ii) complexes [{Ru(phen)(2)}(2)(micro-BL)](4+) (phen = 1,10-phenanthroline) with flexible bridging ligands (BL) bb2 {1,2-bis[4(4'-methyl-2,2'-bipyridyl)]ethane}, bb5 {1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane}, bb7 {1,7-bis[4(4'-methyl-2,2'-bipyridyl)]heptane}, and bb10 {1,10-bis[4(4'-methyl-2,2'-bipyridyl)]decane} have been synthesised. Their binding to a control dodecanucleotide, d(CCGGAATTCCGG)(2), and a tridecanucleotide, d(CCGAGAATTCCGG)(2), which contains a single adenine bulge have been studied using fluorescence displacement assays involving intercalating and groove-binding dyes, equilibrium dialysis and binding affinity chromatography. The fluorescence intercalator displacement (FID) assay indicated that LambdaLambda-[{Ru(phen)(2)}(2)(micro-bb7)](4+) had the greatest binding affinity with all the oligonucleotides, whereas an analogous fluorescence technique using a minor-groove binding dye, equilibrium dialysis and affinity binding chromatography showed that DeltaDelta-[{Ru(phen)(2)}(2)(micro-bb7)](4+) had the strongest binding. An (1)H NMR study of the binding of the DeltaDelta-enantiomer of [{Ru(phen)(2)}(2)(micro-bb7)](4+) to d(CCGAGAATTCCGG)(2) confirmed the selectivity of the metal complex for the bulge site and provided the basis for an energy-minimised binding model of the dinuclear ruthenium complex with the single adenine bulge containing trinucleotide. The binding model demonstrated the ability of the flexibly-linked complex to follow the curvature of the DNA minor groove.
Morgan
Joy L
JL
Discipline of Chemistry, School of Pharmacy & Molecular Sciences, James Cook University, Townsville, Queensland 4811, Australia.
Spillane
Caitriona B
CB
Smith
Jayden A
JA
Buck
Damian P
DP
Collins
J Grant
JG
Keene
F Richard
FR
D001483:Base Sequence; D052160:Benzothiazoles / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004996:Ethidium / Q000737:chemistry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D009942:Organometallic Compounds / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*
D052160:Benzothiazoles; D005456:Fluorescent Dyes; D007211:Indoles; D007364:Intercalating Agents; D009841:Oligonucleotides; D009942:Organometallic Compounds; D010618:Phenanthrolines; D011725:Pyridines; D011804:Quinolines; C051000:thiazole orange; D012428:Ruthenium; D004247:DNA; D004996:Ethidium; C025205:1,10-phenanthroline