DNA binding by a new metallointercalator that contains a proflavine group bearing a hanging chelating unit |
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Authors: | Bazzicalupi Carla Bencini Andrea Bianchi Antonio Biver Tarita Boggioni Alessia Bonacchi Sara Danesi Andrea Giorgi Claudia Gratteri Paola Ingraín Antonio Marchal Secco Fernando Sissi Claudia Valtancoli Barbara Venturini Marcella |
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Institution: | Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. |
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Abstract: | The new bifunctional molecule 3,6-diamine-9-6,6-bis(2-aminoethyl)-1,6-diaminohexyl]acridine (D), which is characterised by both an aromatic moiety and a separate metal-complexing polyamine centre, has been synthesised. The characteristics of D and its ZnII complex (ZnD]) (protonation and metal-complexing constants, optical properties and self-aggregation phenomena) have been analysed by means of NMR spectroscopy, potentiometric, spectrophotometric and spectrofluorimetric techniques. The equilibria and kinetics of the binding process of D and ZnD] to calf thymus DNA have been investigated at I=0.11 M (NaCl) and 298.1 K by using spectroscopic methods and the stopped-flow technique. Static measurements show biphasic behaviour for both D-DNA and ZnD]-DNA systems; this reveals the occurrence of two different binding processes depending on the polymer-to-dye molar ratio (P/D). The binding mode that occurs at low P/D values is interpreted in terms of external binding with a notable contribution from the polyamine residue. The binding mode at high P/D values corresponds to intercalation of the proflavine residue. Stopped-flow, circular dichroism and supercoiled-DNA unwinding experiments corroborate the proposed mechanism. Molecular-modelling studies support the intercalative process and evidence the influence of NH+...O interactions between the protonated acridine nitrogen atom and the oxygen atoms of the polyanion; these interactions play a key role in determining the conformation of DNA adducts. |
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