TY - JOUR
T1 - Copper(II) complexes with tetradentate piperazine-based Ligands
T2 - DNA cleavage and cytotoxicity
AU - Doniz Kettenmann, Sebastian
AU - Nossol, Yvonne
AU - Louka, Febee R.
AU - Legrande, Julia R.
AU - Marine, Elise
AU - Fischer, Roland C.
AU - Mautner, Franz A.
AU - Hergl, Vinja
AU - Kulak, Nora
AU - Massoud, Salah S.
N1 - Funding Information:
Funding: This research was funded by Deutsche Forschungsmeinschaft (DFG) grant number GRK 1582 (S.D.K. and N.K.).
Funding Information:
produce a dinuclear with bridged hydroxido derivatives (Scheme 2). This was supported by the isolation and structural characterization of [(L1)Cu2(µ-OH)(H2O)(OAc)2Cl] [51].
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2
Y1 - 2021/2
N2 - Five-coordinate Cu(II) complexes, [Cu(Ln)X]ClO4/PF6, where Ln = piperazine ligands bearing two pyridyl arms and X = ClO4 − for Ln = L1 (1-ClO4), L2 (2-ClO4), L3 (3-ClO4), and L6 (6-ClO4) as well as [Cu(Ln)Cl]PF6 for Ln = L1 (1-Cl), L4 (4-Cl), and L5 (5-Cl) have been synthesized and characterized by spectroscopic techniques. The molecular structures of the last two complexes were determined by X-ray crystallography. In aqueous acetonitrile solutions, molar conductivity measurements and UV-VIS spectrophotometric titrations of the complexes revealed the hydrolysis of the complexes to [Cu(Ln)(H2O)]2+ species. The biological activity of the Cu(II) complexes with respect to DNA cleavage and cytotoxicity was investigated. At micromolar concentration within 2 h and pH 7.4, DNA cleavage rate decreased in the order: 1-Cl ≈ 1-ClO4 > 3-ClO4 ≥ 2-ClO4 with cleavage enhancements of up to 23 million. Complexes 4-Cl, 5-Cl, and 6-ClO4 were inactive. In order to elucidate the cleavage mechanism, the cleavage of bis(4-nitrophenyl)phosphate (BNPP) and reactive oxygen species (ROS) quenching studies were conducted. The mechanistic pathway of DNA cleavage depends on the ligand’s skeleton: While an oxidative pathway was preferable for 1-Cl/1-ClO4, DNA cleavage by 2-ClO4 and 3-ClO4 predominantly proceeds via a hydrolytic mechanism. Complexes 1-ClO4, 3-ClO4, and 5-Cl were found to be cytotoxic against A2780 cells (IC50 30-40 µM). In fibroblasts, the IC50 value was much higher for 3-ClO4 with no toxic effect.
AB - Five-coordinate Cu(II) complexes, [Cu(Ln)X]ClO4/PF6, where Ln = piperazine ligands bearing two pyridyl arms and X = ClO4 − for Ln = L1 (1-ClO4), L2 (2-ClO4), L3 (3-ClO4), and L6 (6-ClO4) as well as [Cu(Ln)Cl]PF6 for Ln = L1 (1-Cl), L4 (4-Cl), and L5 (5-Cl) have been synthesized and characterized by spectroscopic techniques. The molecular structures of the last two complexes were determined by X-ray crystallography. In aqueous acetonitrile solutions, molar conductivity measurements and UV-VIS spectrophotometric titrations of the complexes revealed the hydrolysis of the complexes to [Cu(Ln)(H2O)]2+ species. The biological activity of the Cu(II) complexes with respect to DNA cleavage and cytotoxicity was investigated. At micromolar concentration within 2 h and pH 7.4, DNA cleavage rate decreased in the order: 1-Cl ≈ 1-ClO4 > 3-ClO4 ≥ 2-ClO4 with cleavage enhancements of up to 23 million. Complexes 4-Cl, 5-Cl, and 6-ClO4 were inactive. In order to elucidate the cleavage mechanism, the cleavage of bis(4-nitrophenyl)phosphate (BNPP) and reactive oxygen species (ROS) quenching studies were conducted. The mechanistic pathway of DNA cleavage depends on the ligand’s skeleton: While an oxidative pathway was preferable for 1-Cl/1-ClO4, DNA cleavage by 2-ClO4 and 3-ClO4 predominantly proceeds via a hydrolytic mechanism. Complexes 1-ClO4, 3-ClO4, and 5-Cl were found to be cytotoxic against A2780 cells (IC50 30-40 µM). In fibroblasts, the IC50 value was much higher for 3-ClO4 with no toxic effect.
UR - http://www.scopus.com/inward/record.url?scp=85100909772&partnerID=8YFLogxK
U2 - 10.3390/inorganics9020012
DO - 10.3390/inorganics9020012
M3 - Article
AN - SCOPUS:85100909772
SN - 2304-6740
VL - 9
SP - 1
EP - 23
JO - Inorganics
JF - Inorganics
IS - 2
M1 - 12
ER -