Copper (II) complexes possessing alkyl-substituted polypyridyl ligands: Structural characterization and in vitro antitumor activity.
In an effort to find alternatives to the antitumor drug cisplatin, a series of copper (II) complexes possessing alkyl-substituted polypyridyl ligands have been synthesized. Eight new complexes are reported herein: μ-dichloro-bis{2,9-di-sec-butyl-1,10-phenanthrolinechlorocopper(II)} {[(di-sec-butylphen)ClCu(μ-Cl)2CuCl(di-sec-butylphen)]}(1), 2-sec-butyl-1,10-phenanthrolinedichlorocopper(II) {[mono-sec-butylphen) CuCl2} (2), 2,9-di-n-butyl-1,10-phenanthrolinedichlorocopper(II) {[di-n-butylphen) CuCl2}(3), 2-n-butyl-1,10-phenanthrolinedichlorocopper(II) {[mono-n-butylphen) CuCl2} (4), 2,9-di-methyl-1,10-phenanthrolineaquadichlorocopper(II) {[di-methylphen) Cu(H2O)Cl2}(5), μ-dichloro-bis{6-sec-butyl-2,2'-bipyridinedichlorocopper(II)} {(mono-sec-butylbipy) ClCu(μ-Cl)2CuCl(mono-sec-butylbipy)} (6), 6,6'-di-methyl-2,2'-bipyridinedichlorocopper(II) {6,6'-di-methylbipy) CuCl2} (7), and 4,4'-dimethyl-2,2'-bipyridinedichlorocopper(II) {4,4'-di-methylbipy) CuCl2} (8). These complexes have been characterized via elemental analysis, UV-vis spectroscopy, and mass spectrometry. Single crystal X-ray diffraction experiments revealed the complexes synthesized with thedi-sec-butylphen ligand (1) andmono-sec-butylbipy ligand (6) crystallized as dimers in which two copper(II) centers are bridged by two chloride ligands. Conversely, complexes 2, 7, and 8 were isolated as monomeric species possessing distorted tetrahedral geometries, and the [(di-methylphen)Cu(H2O)Cl2] (5) complex was isolated as a distorted square pyramidal monomer possessing a coordinating aqua ligand. Compounds 1-8 were evaluated for their in vitro antitumor efficacy. Compounds 1, 5, and 7 in particular were found to exhibit remarkable activity against human derived lung cancer cells, yet this class of copper(II) compounds had minimal cytotoxic effect on non-cancerous cells. In vitro control experiments indicate the activity of the copper(II) complexes most likely does not arise from the formation of CuCl2and free polypyridyl ligand, and preliminary solution state studies suggest these compounds are generally stable in biological buffer. The results presented herein suggest further development of this class of copper-based drugs as potential anti-cancer therapies should be pursued.
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Noah R
NR
Angel
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Raneen M
RM
Khatib
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Julia
J
Jenkins
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Michelle
M
Smith
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Justin M
JM
Rubalcava
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Brian Khoa
BK
Le
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Daniel
D
Lussier
Emory University Winship Cancer Institute, United States.
Zhuo Georgia
ZG
Chen
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States.
Fook S
FS
Tham
University of California, Riverside School of Medicine, Division of Biomedical Sciences, United States.
Emma H
EH
Wilson
University of California, Riverside Department of Chemistry, 501 Big Springs Rd., Riverside, CA 92521, United States. Electronic address: jack.eichler@ucr.edu.
Jack F
JF
Eichler
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D011725:Pyridines; D003300:Copper
Anticancer; Bipyrydine; Copper(II); Phenanthroline; Polypyridyl; Synthesis