An official website of the United States government
The 3d transition metal (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes, supported by anions of sterically demanding β-diketones, 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3), were synthesized and evaluated for their antitumor activity. To assess the biological effects of substituents on phenyl moieties, we also synthesized and investigated the analogous metal(II) complexes of the anion of the less bulky 1,3-diphenylpropane-1,3-dione (HLPh) ligand. The compounds [Cu(LCF3)2], [Cu(LMes)2] and ([Zn(LMes)2]) were characterized by X-ray crystallography. The [Cu(LCF3)2] crystallizes with an apical molecule of solvent (THF) and features a rare square pyramidal geometry at the Cu(II) center. The copper(II) and zinc(II) complexes of diketonate ligands, derived from the deprotonated 1,3-dimesitylpropane-1,3-dione (HLMes), adopt a square planar or a tetrahedral geometry at the metal, respectively. We evaluated the antitumor properties of the newly synthesized (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes against a series of human tumor cell lines derived from different solid tumors. Except for iron derivatives, cellular studies revealed noteworthy antitumor properties, even towards cancer cells endowed with poor sensitivity to the reference drug cisplatin.
more »
« less
This content will become publicly available on June 1, 2026
Synthesis, Reductive Reactivity and Anticancer Activity of Cobalt(III)– and Manganese(III)–Salen Complexes
Mn(III)– and Co(III)–salen complexes (Mn-1 and Co-2) have been synthesized by a simple one-pot procedure through oxidation of Mn(II) and Co(II) precursors in air. X-ray structural analysis reveals that both complexes adopt similar coordination modes, including a typical square planar metal/salen coordination sphere, which is further occupied by two axial ligands, i.e., an acetate anion and a water molecule. Despite their structural similarity, they are not isomorphous given their distinct cell parameters. In the solid-state structures, both complexes exist as hydrogen-bonded dimers through hydrogen bonding interactions between the axially coordinating water molecules and outer O4 cavity from another molecule of the complex. The reductive activity of both complexes has been explored. While the reaction of Mn-1 with potassium triethylborohydride was unsuccessful, leading to a complicated mixture, the use of Co-2 furnished the formation of a novel product (CoK-3) that was isolated as red crystals in reasonable yield. CoK-3 was characterized as a heterometallic dimer involving the coordination of a K+ ion within the O4 cavity of a semi-hydrogenated salen/cobalt complex while the cobalt center has been reduced from Co(III) to Co(II). In addition, an attempt at reducing Co-2 with pinacolborane resulted in the isolation of crystals of Co-4, whose structure was determined as a simple square planar CoII–salen complex. Finally, three complexes (Mn-1, Co-2 and CoK-3) have been investigated for their cytotoxic activities against two human breast cancer cell lines (MCF-7 and MDA-MB 468) and a normal breast epitheliel cell line (MCF-10A), with cisplatin used as a reference in order to discover potential drug candidates that may compete with cisplatin. The results reveal that Co-2 can be a promising drug candidate, specifically for the MCF-7 cancer cells, with minimal damage to healthy cells.
more »
« less
- PAR ID:
- 10592686
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- Chemistry
- Volume:
- 7
- Issue:
- 3
- ISSN:
- 2624-8549
- Page Range / eLocation ID:
- 85
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
To increase the number of potential materials for application as MRI contrast agents, several Cu(II) complexes were synthesized. Cu(II) complexes were chosen because they are less expensive in comparison with the presently used Gd(III), Mn(II) and other agents. Pyridine-2-carboximidamide (1), pyrimidine-2-carboximidamide (2) and pyrazole-2-carboximidamide (3) in the form of different salts along with CuCl2 and NaCl or CuBr2 and NaBr were used to obtain four Cu(II) complexes: dichloro-pyrimidine-2-carboximidamide copper(II) (4), dibromo-pyrimidine-2-carboximidamide copper(II) (5), dichloro-pirazole-2-carboximidamide copper(II) (6), and dibromo-pirazole-2-carboximidamide copper(II) (7). X-ray diffraction analysis revealed that molecular complexes 4–7 contain square planar coordinated Cu(II) atoms and their structures are very similar, as well as their packing in crystals, which allows us to consider them isomorphs. The same synthetic approach to complex preparation where NaCl or NaBr was not used brought us to the formation of dimeric complexes μ-chloro{chloro(pyridine-2-carboximidamide)copper(II)} (8) and μ-chloro{chloro(pyrimidine-2-carboximidamide)copper(II)} (9). In the dimeric complexes, two fragments which were the same as in monomeric complexes 4–7 are held together by bridging Cu-Cl bonds making the coordination of Cu equal to 5 (square pyramid). In dimeric complexes, axial Cu-Cl bonds are 2.7360 and 2.854 Å. These values are Cu-Cl bonds on the edge of existence according to statistical data from CSD. Synthesized complexes were characterized by IR spectroscopy, TGA, PXRD, EPR, and quantum chemical calculations. The higher thermal stability of monomer pyrimidine-based complexes with Cl and Br substituents makes them more prospective for further studies.more » « less
-
Oxidation of distorted square-planar perfluoropinacolate Co compound [Co II (pin F ) 2 ] 2− , 1 , to [Co III (pin F ) 2 ] 1− , 2 , is reported. Rigidly square-planar 2 has an intermediate-spin, S = 1, ground state and very large zero-field splitting (ZFS) with D = 67.2 cm −1 ; | E | = 18.0 cm −1 , ( E / D = 0.27), g ⊥ = 2.10, g ‖ = 2.25 and χ TIP = 1950 × 10 −6 cm 3 mol −1 . This Co( iii ) species, 2 , reacts with ROS to oxidise two (pin F ) 2− ligands to form tetrahedral [Co II (Hpfa) 4 ] 2− , 3 .more » « less
-
We report on the synthesis and characterization of Mn(III) chloride (MnIIICl3) complexes coordinated with N-oxide ylide ligands, namely trimethyl-N-oxide (Me3NO) and pyridine-N-oxide (PyNO). The compounds are reactive and, while isolable in the solid-state at room temperature, readily decompose into Mn(II). For example, “[MnIIICl3(ONMe3)n]” decomposes into the 2D polymeric network compound complex salt [MnII(µ-Cl)3MnII(µ-ONMe3)]n[MnII(µ-Cl)3]n·(Me3NO·HCl)3n (4). The reaction of MnIIICl3 with PyNO forms varied Mn(III) compounds with PyNO coordination and these react with hexamethylbenzene (HMB) to form the chlorinated organic product 1-cloromethyl-2,3,4,5,6-pentamethylbenzene (8). In contrast to N-oxide coordination to Mn(III), the reaction between [MnIIICl3(OPPh3)2] and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) resulted in electron transfer-forming d5 manganate of the [TEMPO] cation instead of TEMPO–Mn(III) adducts. The reactivity affected by N-oxide coordination is discussed through comparisons with other L–MnIIICl3 complexes within the context of reduction potential.more » « less
-
Abstract Reduction of the cobalt(II) chloride complex, Ph2B(tBuIm)2Co(THF)Cl (1) in the presence oftBuN≡C affords the diamagnetic, square planar cobalt(I) complex Ph2B(tBuIm)2Co(C≡NtBu)2(2). This is a rare example of a 16‐electron cobalt(I) complex that is structurally related to square planar noble metal complexes. Accordingly, the electronic structure of2, as calculated by DFT, reveals that the HOMO is largely dz2in character. Complex2is readily oxidized to its cobalt(II) congener [Ph2B(tBuIm)2Co(C=NtBu)2]BPh4(3‐BPh4), whose EPR spectral parameters are characteristic of low‐spin d7with an unpaired electron in an orbital of dz2parentage. This is also consistent with the results of DFT calculations. Despite its 16‐electron configuration and the dz2parentage of the HOMO, the only tractable reactions of2involve one electron oxidation to afford3.more » « less
