title: DNA binding of a proflavine derivative bearing a platinum hanging residue.
abstract: New platinum(II) complex of 3,6-diamine-9-[6,6-bis(2-aminohethyl)-1,6-diaminohexyl]acridine, AzaPt, has been synthesised and characterised. Behaviour of AzaPt in solution (protonation and possible self-aggregation phenomena) has been investigated by spectral methods (absorbance and fluorescence) at I=0.1M and 25°C, and the equilibrium parameters of binding to calf thymus DNA have been established. Two different modes of DNA binding by the complex were detected, which depend on the polymer to dye molar ratio (P/D). At relatively low P/D values the mode was interpreted as binding by the polyamine residue external to the base pairs, while at high P/D values the binding corresponds to intercalation of the proflavine residue. Such interpretation is supported by the observed salt effect on binding and the temperature variation of the binding constants, which allowed estimating the ΔH and ΔS values contributions. Spectrophotometric analysis of the long time range binding revealed that AzaPt is involved in a slow reaction, interpreted as an attack by the platinum ion on the nucleobases. The time constant for such interaction was calculated and found to be the same order of magnitude as for processes responsible for the action of anti-tumour drugs that do covalently bind to polynucleotides.
authors.affiliation: Dipartimento di Chimica Ugo Schiff, Università di Firenze, Via della Lastruccia 3, Sesto Fiorentino, Italy. s.biagini@unifi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Biagini
authors.forename: Antonio
authors.initials: A
authors.lastname: Bianchi
authors.forename: Tarita
authors.initials: T
authors.lastname: Biver
authors.forename: Alessia
authors.initials: A
authors.lastname: Boggioni
authors.forename: Igor V
authors.initials: IV
authors.lastname: Nikolayenko
authors.forename: Fernando
authors.initials: F
authors.lastname: Secco
authors.forename: Marcella
authors.initials: M
authors.lastname: Venturini
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D007364:Intercalating Agents / Q000737:chemistry; D007700:Kinetics; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry; D011370:Proflavine / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D007364:Intercalating Agents; D009944:Organoplatinum Compounds; D010984:Platinum; D004247:DNA; C427203:calf thymus DNA; D011370:Proflavine