Efficient hydrolytic cleavage of plasmid DNA by chloro-cobalt(ii) complexes based on sterically hindered pyridyl tripod tetraamine ligands: synthesis, crystal structure and DNA cleavage

Abstract

Four new cobalt(ii) complexes [Co(6-MeTPA)Cl]ClO4/PF6 (2/2a), [Co(6-Me2TPA)Cl]ClO4/PF6 (3/3a), [Co(BPQA)Cl]ClO4/PF6 (4/4a) and [Co(BQPA)Cl]ClO4/PF6 (5/5a) as well as [Co(TPA)Cl]ClO4 (1) where TPA = tris(2-pyridylmethyl)amine, 6-MeTPA = ((6-methyl-2-pyridyl)methyl)bis(2-pyridylmethyl)amine, 6-Me2TPA = bis(6-methyl-2-pyridyl)methyl)-(2-pyridylmethyl)amine, BPQA = bis(2-pyridylmethyl)-(2-quinolylmethyl)-amine and BQPA = bis(2-quinolylmethyl)-(2-pyridylmethyl)amine were synthesized and structurally characterized. Single crystal X-ray crystallography confirmed the distorted trigonal bipyramidal geometries of complexes 2a-5a. Spectrophotometric titrations and conductivity measurements of the complexes in the CH3CN-H2O mixture showed that the chloro complexes exist in equilibrium with the corresponding hydrolyzed aqua species, [Co(L)(H2O)](2+). The pKa values of the coordinated H2O in aqua complexes vary from 8.4 to 8.7 (37 °C). The interactions of the complexes (1-5) with DNA have been investigated at pH = 7.0 and 9.0 (10 mM Tris-HCl buffer) and 37 °C where very high catalytic cleavage was observed. Under pseudo Michaelis-Menten kinetic conditions, the catalytic rate constants, kcat, decrease in the order 4>2>5>1>3. At pH 7.0 (10 mM Tris-HCl buffer) and 37 °C, the kcat value for complex 4 (6.02 h(-1)), where [Co(BPQA)(H2O)](2+) is the major species, corresponds to 170 million rate enhancement over the non-catalyzed DNA. Electrophoretic experiments conducted in the presence and absence of radical scavengers (DMSO, KI, NaN3) ruled out the oxidative mechanistic pathway of the reaction and suggested that the hydrolytic mechanism is the preferred one. This finding was in agreement with the observed increase in the kcat values at pH 9.0 compared to the corresponding values at pH 7.0 as a result of the increased concentration of the reactive hydroxo species, [Co(L)(OH)](+). The reactivity of the synthesized complexes in catalyzing the DNA cleavage is discussed in relation to the steric effect imposed by the coordinated pyridyl ligand around the central cobalt(ii) center.

Six-coordinate Iron(II) and Cobalt(II) paraSHIFT Agents for Measuring Temperature by Magnetic Resonance Spectroscopy

“…The bond lengths of [Co(MPT)] 2+ are typical for Co(II) high-spin as supported by literature values. 79 Further examination of the Co–N Pyr and Co–N TACN bond lengths, which are ≥2.197(2) A and ≥2.153(2) A, respectively, demonstrates their similarity to the ones observed for the high-spin [Fe(MPT)](CF 3 SO 3 ) 2 (Table 2). …”

Five-coordinate metal(II) complexes based pyrazolyl ligands

“…Increase the steric effect at the N-donor atoms of the coligand results in increasing distortion from the above adapted geometry. With Co(II) complexes 35-40 of tripod tetradentate amine ligands the TPB geometry is retained with different degree of distortion (s = 0.70-1.0) [1,29,45]. However, with Cu(II) compounds which were derived from tetraamines the picture is more complicated and depends largely on the chelate ring size and steric environment imposed in the coligand.…”

“…In general, it has been pointed out that SP geometries are stabilized in complexes that are constructed from ligands with the capability of forming six-membered chelate rings [34][35][36] as this was the case in complexes 2-5.…”

Synthesis, Characterization, and Cytotoxicity of the Cobalt (III) Complex with N,N‐Diethyl‐4‐(2,2′:6′,2′′‐terpyridin‐4′‐yl)aniline

“…The results agreed with the flow cytometric analysis for ROS generation in T‐24 cells. In addition, the alternative possibility that the Co(III) complex 1 might bind to DNA and be reduced by thiols and/or ascorbic acid reducing species abundant in cells, thus generating ROS close to DNA to cause DNA damage, very similar to that of [Co(6‐MeTPA)Cl]‐ClO 4 /PF 6 , [Co(6‐Me 2 TPA)Cl]ClO 4 /PF 6 , [Co(BPQA)Cl]ClO 4 /PF 6 , [Co(BQPA)Cl]ClO 4 /PF 6 , [Co(TPA)Cl]ClO 4 , [Co(Pyimpy)‐Cl 2 ], [Co(Pyimpy) 2 ](ClO4) 2 , [Co(Pamp)Cl 2 ], [Co(Pamp) 2 ]‐(ClO 4 ), [Cu(p‐4‐bmb)(Ac) 2 ] 2 , and [Co(p‐4‐bmp)Cl 2 ] 2 . Taken together, it can be seen that the Co(III) complex 1 interfered with mitochondrial function, led to the accumulation of ROS and cause DNA damage, and consequently induced apoptosis …”