Efficient Increase of DNA Cleavage Activity of a Diiron(III) Complex by a Conjugating Acridine Group

Abstract

A new diferric complex, Fe 2 L b , in which a DNA intercalator (acridine) is linked to a precursor diferric complex (Fe 2 L a ), has been designed and synthesised as a hydrolytic cleaving agent of DNA. Compared with Fe 2 L a (without the DNA inter- -(3,5-bis{[(2-hydroxybenzyl) (pyridin-2-yl)methylamino]-methyl}-4-hydroxybenzyl)pentanamide] leads to a 14-fold increase in the cleavage efficiency of plasmid DNA due to the binding interaction between DNA and the acridine moiety. The interaction has been demonstrated by UV/Vis absorption, CD spectroscopy, viscidity experiments and thermal denaturation studies. The hydrolytic mechanism is supported by evidence from T4 DNA ligase assay, reactive oxygen spe-

Iron(III) Complexes of Metal‐Binding Copolymers as Proficient Catalysts for Acid Hydrolysis of Phosphodiesters and Oxidative DNA Cleavage – Insight into the Rational Design of Functional Metallopolymers

“…The catalytic proficiency at pH 5.3 and the rate constant at pH 8.0 are comparable or better than catalytic BNPP hydrolysis by several homogeneous and heterogeneous metal complexes and polymers under various conditions. For example, the mononuclear complexes [(ethylenediamine) 2 [27] an acridine-containing di-Fe complex exhibits k cat = (5.2 Ϯ 0.2) ϫ 10 -5 s -1 and K m = 3.1 Ϯ 0.1 m at pH 7.36 and 50°C; [28] the metallopolymers Cu II (vbpy) [29] and Cu II (adenine) show k cat = 2.3 ϫ 10 -5 s -1 (at 25°C) and k cat = 2.23 ϫ 10 -6 s -1 (at 30°C) at pH 8.0; [30] Cu II -P1 [4] and Fe III -Chelex resin [31] exhibit k cat = 8.30 Ϯ 0.35 ϫ 10 -6 s -1 and k cat = 1.8 ϫ 10 -7 s -1 at 25°C and pH 8.0 and 9.0, respectively. Being able to perform acid hydrolysis of phosphoesters is catalytically significant, as the phosphate/phosphoesters products are acidic and can potentially slow down the reaction rate by lowering the pH.…”

“…complexes were previously reported to exhibit oxidative [35] and hydrolytic [28,36] activities toward DNA cleavage. The plasmid does not change for a period of 2 h in the absence of H 2 O 2 in solution, reflecting that hydrolytic cleavage does not takes place to a noticeable extent under the experimental conditions and reagent concentrations.…”

Multinuclear Non‐Heme Iron Complexes for Double‐Strand DNA Cleavage

“…Optional purification was achieved by sizeexclusion chromatography (Sephadex LH 20/MeOH) or preparative RP-HPLC. (27): The Boc-protected di-N4Py ligand 25 (0.417 g, 0.337 mmol) was taken up in CH 2 Cl 2 (9 mL), and then TFA (1 mL) was carefully added. After stirring the mixture overnight at room temperature, 2 m aqueous NaOH solution was added until pH > 10.…”

“…[27] Recently, we reported on a binuclear iron complex, based on N4Py, that showed significantly enhanced double-strand cleavage activity. [28] Multinuclear copper complexes have also been investigated in relation to DNA cleavage.…”

Synthesis, crystal structure, magnetic property, and nuclease activity of a binuclear iron(III) complex

“…Among the active transition metal species, dinuclear, and polynuclear complexes generally give higher cleavage rates provided that the ligand holds the metal centers in an appropriate geometry [2][3][4][5][6][7][8][9]. Compared with mononuclear complexes, dinuclear complexes have higher activity as a result of the cooperative interaction of metal ions in stabilizing the transition state of phosphodiester cleavage.…”