Kinetic and equilibrium studies on the polyazamacrocycle neotetren: metal-complex formation and DNA interaction.
The macrocyclic polyamine 2,5,8,11,14-pentaaza[15]-[15](2,9)[1,10]phenanthrolinophane (neotetren) is studied in its ability to coordinate Cu(ii) even at very low pH values and to interact, as a metal complex, with DNA. The kinetics and equilibria for 1 : 1 and 2 : 1 metal-ligand complexes formation are studied by the stopped-flow method and UV spectrophotometry. Differently protonated complexes are formed, with rate constants much lower than that of water exchange at copper(II) and other Cu(II)/amine systems, this behaviour being ascribed to ring effects and intra-molecular hydrogen bonds. Concerning the DNA/copper(II)-neotetren complexes interaction, analysis of data suggests an intercalative mode of binding. The kinetic results for both DNA/CuL and DNA/Cu(2)L systems agree with the sequence D + S <-->D,S <-->DS where the metal complexes (D) react with the DNA sites (S) leading to fast formation of an externally bound form (D,S) which is converted into an intercalated complex (DS). A very slow process is also detected and ascribed to a conformational change in the polynucleotide secondary structure where the metal centre plays a crucial role. Chromatographic experiments demonstrate that both the investigated Cu(II)/L complexes are able to cleave DNA, but only in the presence of hydrogen peroxide.
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, 56126, Pisa, Italy. tarita@dcci.unipi.it
Tarita
T
Biver
Dario
D
Lombardi
Fernando
F
Secco
Maria Rosaria
MR
Tiné
Marcella
M
Venturini
Andrea
A
Bencini
Antonio
A
Bianchi
Barbara
B
Valtancoli
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry*; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D010618:Phenanthrolines; D011073:Polyamines; D003300:Copper; D004247:DNA