title: Supramolecular approach to enantioselective DNA recognition using enantiomerically resolved cationic 4-amino-1,8-naphthalimide-based Tröger's bases.
abstract: The synthesis and photophysical studies of two cationic Tröger's base (TB)-derived bis-naphthalimides 1 and 2 and the TB derivative 6, characterized by X-ray crystallography, are presented. The enantiomers of 1 and 2 are separated by cation-exchange chromatography on Sephadex C25 using sodium (-)-dibenzoyl-l-tartarate as the chiral mobile phase. The binding of enantiomers with salmon testes (st)-DNA and synthetic polynucleotides are studied by a variety of spectroscopic methods including UV/vis absorbance, circular dichroism, linear dichroism, and ethidium bromide displacement assays, which demonstrated binding of these compounds to the DNA grooves with very high affinity (K ∼ 10(6) M(-1)) and preferential binding of (-)-enantiomer. In all cases, binding to DNA resulted in a significant stabilization of the double-helical structure of DNA against thermal denaturation. Compound (±)-2 and its enantiomers possessed significantly higher binding affinity for double-stranded DNA compared to 1, possibly due to the presence of the methyl group, which allows favorable hydrophobic and van der Waals interactions with DNA. The TB derivatives exhibited marked preference for AT rich sequences, where the binding affinities follow the order (-)-enantiomer > (±) > (+)-enantiomer. The compounds exhibited significant photocleavage of plasmid DNA upon visible light irradiation and are rapidly internalized into malignant cell lines.
authors.affiliation: School of Chemistry and Trinity Biomedical Sciences Institute, University of Dublin , Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Swagata
authors.initials: S
authors.lastname: Banerjee
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Bright
authors.forename: Jayden A
authors.initials: JA
authors.lastname: Smith
authors.forename: Jeremy
authors.initials: J
authors.lastname: Burgeat
authors.forename: Miguel
authors.initials: M
authors.lastname: Martinez-Calvo
authors.forename: D Clive
authors.initials: DC
authors.lastname: Williams
authors.forename: John M
authors.initials: JM
authors.lastname: Kelly
authors.forename: Thorfinnur
authors.initials: T
authors.lastname: Gunnlaugsson
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002412:Cations / Q000737:chemistry*; D002460:Cell Line; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D053837:DNA Cleavage / Q000528:radiation effects*; D006801:Humans; D008027:Light; D015394:Molecular Structure; D053644:Naphthalimides / Q000138:chemical synthesis* / Q000737:chemistry; D055668:Photochemical Processes; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry; D012474:Salmon; D013237:Stereoisomerism
chemical_list: D002412:Cations; D053644:Naphthalimides; D015363:Quinolones; C086538:4-amino-1,8-naphthalimide; D004247:DNA; D015057:1-Naphthylamine