Efficient Artificial Nucleases for Mediating DNA Cleavage Based on Tuning the Steric Effect in the Pyridyl Derivatives of Tripod Tetraamine‐Cobalt(II) Complexes. Issue 20 (14th May 2018)

• Record Type: Journal Article
• Authors: Kettenmann, Sebastian Doniz; Louka, Febee R.; Marine, Elise; Fischer, Roland C.; Mautner, Franz A.; Kulak, Nora; Massoud, Salah S.
• Is Part Of: European journal of inorganic chemistry. Issue 20/21(2018)
• Page Start: 2322
• Page End: 2338
• Publication Date: 2018-05-14
• Subjects: Cobalt -- DNA cleavage -- Hydrolytic cleavage -- Tripod amines -- Crystal structures; Chemistry, Inorganic -- Periodicals; Organometallic chemistry -- Periodicals; Bioinorganic chemistry -- Periodicals; Solid state chemistry -- Periodicals; 546
• DOI: 10.1002/ejic.201800276
• Languages: English
• ISSNs: 1434-1948

Abstract

Abstract : Four cobalt(II) complexes [Co(L 1 )Cl]PF6 /ClO4 (C1‐PF6 /C1‐ClO4 ), [Co(L 2 )Cl]PF6 (C2‐PF6 ), [Co(L 3 )Cl]PF6 /ClO4 · H2 O· CH3 OH (C3‐PF6 /C3‐ClO4 · H2 O· CH3 OH) and [Co(L 4 )Cl]PF6 · 2H2 O (C4‐PF6 · 2H2 O), in which L1–L4 refer to [(3, 5‐dimethyl‐4‐methoxy‐2‐pyridylmethyl)bis(2‐pyridylmethyl)]amine, [(3, 4‐dimethoxy‐2‐pyridylmethyl)‐(2‐pyridylmethyl)]amine, [bis(3, 5‐dimethyl‐4‐methoxy‐2‐pyridylmethyl)‐(2‐pyridylmethyl)]amine and {[bis(3, 4‐dimethoxy‐2‐pyridyl)methyl]‐(2‐pyridylmethyl)}amine, respectively, were synthesized and structurally characterized. Single‐crystal X‐ray crystallography confirmed the trigonal bipyramidal geometries of the complexes. In aqueous acetonitrile solution, the green complexes dissolve with the formation of a yellow solution with biphasic kinetic behavior. In 60 % H2 O/CH3 CN (by volume) and 25 °C, the first step corresponds to the rapid formation of [Co(L)(CH3 CN)] 2+ ( ka = 0.16–2.0 min –1 ) followed by a slow conversion into [Co(L)(H2 O)] 2+ ( kb = 6.3 × 10 –3 –0.10 min –1 ), where the two species exist in equilibrium. The spectrophotometric and conductometric titrations of the complexes were consistent with the proposed equilibrium. The coordinated H2 O in the aqua complexes, [Co(L)(H2 O)] 2+ have p K a values ranging from 8.3 to 8.5 at 25 °C. All complexes cleaved plasmid DNA at micromolar concentrations within 2 h at 37 °C and pH 7.0 under hydrolytic conditions. Compared to the uncatalyzed cleavage of DNA, rate enhancements of up to 100 million were achieved in case of complex C4‐PF6 . Abstract : Chlorido‐cobalt(II) complexes were synthesized from tripodal tetraamine pyridyl derivatives and structurally characterized. Under physiological conditions, the complexes exhibit dramatic rate enhancement for DNA cleavage (10–100 million‐fold) compared to the uncatalyzed reaction. The role of the steric effect in the pyridal groups in the DNA cleavage process was explored.