DNA binding and nuclease activity of cationic iron(IV) and manganese(III) corrole complexes

Abstract

Cationic meso(4-N-methylpyridyl)-based metallocorroles, μ-oxo iron corrole dimer (1b) and manganese corrole monomer (2b), were synthesized and characterized. The interactions of these two metal corrole complexes with CT-DNA were studied by UVvisible, fluorescence and circular dichroism spectroscopic methods, as well as by viscosity measurements. The results revealed that 1b interacts with CT-DNA in a difunctional binding mode, i.e. non-classical intercalation and outside groove binding with H-aggregation, while 2b can interact with CT-DNA via an outside groove binding mode only. The binding constants K b of 1b and 2b were 4.71 × 10 5 M À1 and 2.17 × 10 5 M À1 , respectively, indicating that 1b can bind more tightly to CT-DNA than 2b. Furthermore, both complexes may cleave the supercoiled plasmid DNA efficiently in the presence of hydrogen peroxide or tert-butyl hydroperoxide (TBHP), albeit 1b exhibited a little higher efficiency. The inhibitor tests suggested that singlet oxygen and high-valent (oxo)iron(VI) corrole or (oxo)manganese(V) corrole might be the active intermediates responsible for the oxidative DNA scission. Figure 2. UV-visible spectral changes of 1b in 5 mM Tris-HCl/50 mM NaCl buffer (pH 5), t = 0 (dashed line), 5, 10, 15 and 30 min.Figure 10. Absorption spectra of (a) 1b (20 μM) and (b) 2b (20 μM) in 50 mM Tris-HCl/18 mM NaCl buffer (pH 7.2) in the presence of TBHP or H 2 O 2 at different times. (a) [H 2 O 2 ] = [TBHP] = 10 μM; (b) [H 2 O 2 ] = [TBHP] = 20 mM.

DNA/HSA interaction and nuclease activity of an iron(III) amphiphilic sulfonated corrole

“…To date, only a few reports about the binding behavior of corrole with HSA are available (11,13,27,28). In connection with our previous work on the nuclease activity of metal corrole (10,18,19,29,30), we here report the DNA-binding, HSA interaction and nuclease-like activity of an iron-sulfonated corrole Fe-SC ( Fig. 1).…”

Photocytotoxicity and G‐quadruplex DNA interaction of water‐soluble gallium(III) tris(N‐methyl‐4‐pyridyl)corrole complex

“…DNA is the primary intracellular target of anticancer drugs, whose interactions with small molecules can cause damage to cancerous cells by blocking their further division and ultimately resulting in tumor cell apoptosis . In recent years, the investigation of the interactions between corroles and DNA, including G‐quadruplex and double‐helix DNA, has become of considerable interest owing to their importance for developing biomedicines. To investigate the DNA binding abilities of corrole 3 , four different types of DNA, namely c‐MYC G‐quadruplex DNA (parallel), ct‐DNA (duplex), Hras G‐quadruplex DNA (antiparallel) and htg22 G‐quadruplex DNA (hybrid‐type), were selected as model DNAs.…”

“…To investigate the DNA binding abilities of corrole 3 , four different types of DNA, namely c‐MYC G‐quadruplex DNA (parallel), ct‐DNA (duplex), Hras G‐quadruplex DNA (antiparallel) and htg22 G‐quadruplex DNA (hybrid‐type), were selected as model DNAs. The binding constants were measured using the UV–visible spectroscopy titration method, and the results are listed in Table . Gallium corrole 3 exhibits a higher binding affinity to G‐quadruplex DNA than duplex ct‐DNA.…”

“…Inspired by these findings and continuing our efforts in the research of the bioinorganic chemistry of corroles, we here report the tumor cell photocytotoxicity of a water‐soluble cationic gallium(III) pyridylcorrole, namely 5,10,15‐tris( N ‐methyl‐4‐pyridyl)corrolatogallium(III) ( 3 ; Scheme ). The cytostatic action of gallium(III) corrole 3 was investigated using flow cytometry and fluorescence microscopy.…”

“…Absorption spectra were recorded at room temperature after each successive addition of DNA (0–50 μM) and incubated for 2 min for three titrations at least in the range 300–800 nm. The binding constants were obtained using absorption spectral titration data (at 487 nm) using a previously reported method …”