The interaction of native calf thymus DNA with FeIII-dipyrido[3,2-a:2′,3′-c]phenazine

Abstract

a b s t r a c tThe mono and bis dipyrido[3,2-a:2 0 ,3 0 -c]phenazine (dppz) adducts of iron(III) chloride, i.e. [Fe(dppz)]Cl 3 and [Fe(dppz) 2 ]Cl 3 , have been synthesized and characterized. The interaction of the Fe III dppz hydrolyzed aquo complex with native calf thymus DNA has been monitored as a function of the metal complex-DNA molar ratio, by variable temperature UV absorption spectrophotometry, circular dichroism (CD) and fluorescence spectroscopy. The results obtained in solution at various ionic strength values give support for a tight intercalative binding of the Fe III dppz cation with DNA. In particular, the appearance of induced CD bands, caused by the addition of Fe III dppz, indicate the existence of a rigid metal complex-DNA-binding leading to dominating chiral organization of Fe III dppz species within the DNA double helix. The trend of selected CD bands with the molar concentration of Fe III dppz emphasizes that the presence of high amounts of metal complex induces also the formation of DNA-Fe III dppz supramolecular aggregates in solution. The analysis of fluorescence measurements allowed us to calculate a value of the intercalative binding constant comparable to that obtained by UV spectrophotometric titration. Finally, the temperature dependence of the absorbance at 258 nm shows that the metal complex strongly increases the DNA melting temperature already at metal complex-DNA molar ratio equal to 0.25 suggesting that metal complex intercalation effectively hinders DNA denaturation. Overall, the results of the present study point out that the Fe III dppz aquo complex has DNA-binding properties analogous to those previously reported for the tris-chelate Fe II (phen) 2 dppz complex (phen = 1,10-phenantroline).

Pyrophosphate-bridged complexes with picomolar toxicity

“…EB is weakly fluorescent; upon complexation with DNA it emits intense fluorescence light as a consequence of the strong intercalation of EB between adjacent DNA base pairs [68,69]. It has been extensively reported that the enhanced fluorescence of the EB-DNA complex can be quenched by the addition of a second molecule [70,71].…”

(Dipyrido[3,2-a:2′,3′-c]phenazine)(glycinato)copper(II) perchlorate: A novel DNA-intercalator with anti-proliferative activity against thyroid cancer cell lines

“…The dppz ligand was synthesized and characterized as reported [28,54]. [Cu(gly)dppz]ClO 4 (1) (gly = glycinato) was synthesized by modifying a general synthetic method previously reported [33,37].…”

“…4, shows an intense band at 275 nm and a weaker multiplet in the range 340-400 nm, which is the typical infra-ligand (IL) band of coordinated dppz [28]. Such IL band was used to monitor the interaction with DNA, because the latter shows no absorption in such wavelength range.…”

“…4 as (ε a −ε f )/(ε b −ε f ) vs the molar concentration of DNA in monomeric units (DNA phosphate ) and analyzed by Eqs. (1a) and (1b) [28]. In Eqs.…”

“…Such compounds, in particular [Ru(phen) 2 dppz] 2+ , have been recently used in cellular imaging studies and for virus tracking [23]. Indeed, all known metal complexes of dppz, independently of the nature of the ancillary ligands, are strong intercalating agents, with values of DNA-binding constants within 10 4 -10 7 M −1 [14,[24][25][26][27][28]. Furthermore, it has been recently shown that a cationic derivative of the dppz ligand shows analogous water solubility and DNA-binding constant of the mentioned dppz metal complexes [29,30].…”