DNA binding by a new metallointercalator that contains a proflavine group bearing a hanging chelating unit.
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.
Bazzicalupi
Carla
C
Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.
Bencini
Andrea
A
Bianchi
Antonio
A
Biver
Tarita
T
Boggioni
Alessia
A
Bonacchi
Sara
S
Danesi
Andrea
A
Giorgi
Claudia
C
Gratteri
Paola
P
Ingraín
Antonio Marchal
AM
Secco
Fernando
F
Sissi
Claudia
C
Valtancoli
Barbara
B
Venturini
Marcella
M
D000818:Animals; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D011370:Proflavine / Q000737:chemistry*; D011522:Protons; D012492:Salts / Q000737:chemistry; D017186:Titrimetry; D015032:Zinc / Q000737:chemistry*
D002614:Chelating Agents; D008024:Ligands; D011522:Protons; D012492:Salts; D004247:DNA; C427203:calf thymus DNA; D011370:Proflavine; D004264:DNA Topoisomerases, Type I; D015032:Zinc