Ternary Copper Complexes Research Articles

Interaction of a new copper(II) complex by bovine serum albumin and dipeptidyl peptidase-IV

Dipeptidyl peptidase-IV (DPP-IV) is one of the mammalian serine proteases participated in the pathogenesis of diseases and DPP-IV inhibitors are now widely used as antidiabetic drugs. A new water soluble ternary copper (II) complex,-[Cu(py-phen) (phe) (H2O)]NO3·H2O-(py-phen:pyrazino[2,3f][1,10]phenanthroline, phe:phenylalanine), has been synthesized and characterized by CHN analysis, ESI-MS, FTIR and single-crystal X-ray diffraction techniques. Fluorescence spectroscopy was researched to study the interaction between the complex and bovine serum albumin (BSA) and dipeptidyl peptidase-IV (DPP-IV). Chromophore of BSA and DPP-IV enzyme is changed upon addition of the complex. Additionally, the complex was shown to have promising inhibitory activities against DPP-IV with lower IC50 value. This study may provide new insights into the development of effective agents against diabetes.

Advanced Electron Paramagnetic Resonance Studies of a Ternary Complex of Copper, Amyloid-β, and a Chemical Regulator.

Although there has been extensive effort to develop chemical regulators, progress has been static, in part because of these regulators' unclear mechanisms. Here, we report using advanced electron paramagnetic resonance (EPR) spectroscopy to obtain the first molecular-level structural information regarding a ternary complex of CuII-amyloid-β (Aβ) with a chemical regulator that can specifically modulate Cu-induced Aβ aggregation. Our advanced EPR spectroscopic results revealed that a chemical regulator (1) for CuII-Aβ1-16 disrupted the coordination environment of CuII in Aβ, resulting in the detachment of the primary amine at the N-terminal and a carbonyl group between Asp1 and Ala2 from the CuII center and the subsequent formation of a ternary complex, chemical regulator-CuII-Aβ1-16. Therefore, our results demonstrate how a chemical regulator interacts with metal-Aβ at the molecular level. These findings provide novel insight into working mechanisms and thereby contribute to the establishment of a rational design for chemical regulators of metal-Aβ complexes.

Recombinogenic Effect of the Ternary Complex of Copper(II) with Doxycycline and 1,10-Phenanthroline on Somatic Cells of Drosophila melanogaster

In the search for new anti-tumor agents, exploiting features such as the flexibility of coordination modes of metals have become an alternative strategy for synthesizing pharmaceuticals. It has been shown that the CuDP (copper(II), doxycycline, and 1,10-phenanthroline) complex cleaves DNA strands by an oxidative mechanism and by intercalating the major groove, resulting in a cytotoxic action. The objective of this study was to assess the mutagenic/recombinogenic effects of the CuDP complex in vivo using the SMART (Somatic Mutation and Recombination Test) in Drosophila melanogaster. Treatments were carried out with third instar larvae at the standard cross and high bioactivation cross using three concentrations of CuDP (6.92, 13.84 or 27.67 mM). The mutagenic doxorubicin (0.4 mM) was used as a positive control and reverse osmosis water as a negative control. For each compound, marked trans-heterozygous and balanced heterozygous individuals were analyzed to determine the mutational and recombinogenic events occurring in the cells. We found that CuDP significantly increased the frequencies of mutant cells in both standard and high bioactivation crosses, mostly by induction of recombination. These data show that CuDP is a direct recombinogenic agent that is independent of bioactivation.

Newly synthesized Cu(II) pyrazino[2,3‐f][1,10]phenanthroline complexes as potential anticancer candidates

New binary and ternary copper(II) complexes, [Cu(py‐phen)2(NO3)]NO3 (1), [Cu2(py‐phen)2(gly)2(NO3)2(H2O)2]⋅3H2O (2) and [Cu2(py‐phen)2(tyr)2(H2O)2](NO3)2⋅3H2O (3) (py‐phen: pyrazino[2,3‐f][1,10]phenanthroline; gly: glycine; tyr: tyrosine), have been synthesized and characterized using CHN analysis, electrospray ionization mass spectrometry, Fourier transform infrared spectroscopy and single‐crystal X‐ray diffraction. Interaction of these complexes with calf thymus DNA has been investigated using absorption spectral titration, ethidium bromide and Hoechst 33258 displacement assay and thermal denaturation measurements. These complexes were found to be efficient cleaving agents and cleavage reactions were mediated by hydrolytic and oxidative pathways. The interaction between these complexes and bovine serum albumin (BSA) was investigated using electronic absorption and fluorescence spectroscopy. The experimental results show that the fluorescence quenching mechanism of these complexes and BSA is a static quenching process. Furthermore, in vitro cytotoxicities of these complexes against tumour cell lines (Caco‐2, MCF‐7 and A549) and healthy cell line (BEAS‐2B) showed that they exhibited anticancer activity with low IC50 values. These complexes were markedly active against the cell lines and can be good drug candidates that are effective and safe for healthy tissue.

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Mixed Ternary Mononuclear Copper(II) Complexes Based on Valproic Acid with 1,10-Phenanthroline and 2,2’-Bipyridine Ligands: DNA Interaction and Cytotoxicity in V79 Cells

This paper reports the DNA interaction and cytotoxicity of binary and ternary copper(II) complexes of valproic acid with phenanthroline or bipyridine and the complementary characterization of Cu(Valp)2Bipy by crystallography. Circular dichroism, plasmid and oligonucleotide assays have shown that the complexes interact with DNA in different manners and are able to cleave plasmid DNA and oligonucleotides at concentrations from 10 to 1000 mol L-1. The plasmid DNA cleavage is enhanced 650, 375 and 285 times by photo activation with UVB light for the complexes Cu(Valp)2Phen, Cu(Valp)2Bipy and Cu2(Valp)4, respectively. Cytotoxicity assays demonstrated that V79 cells were more sensitive to CuII derivatives than sodium valproate as evaluated by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) and clonogenic assays, where the cytotoxic profile of the compounds was: Cu(Valp)2Phen higher than Cu(Valp)2Bipy, higher than Cu2(Valp)4. Therefore, we report two copper complexes, which interact with DNA and promote its cleavage, leading to an enhanced cytotoxicity when compared to valproic acid.

Ternary copper (II) complex induced cell cycle arrest and apoptosis in human breast (MDA-MB-231) and colon (HT-29) cancer cells

Event Abstract Back to Event Ternary copper (II) complex induced cell cycle arrest and apoptosis in human breast (MDA-MB-231) and colon (HT-29) cancer cells Jhi Biau Foo1*, Xian Wei Teo1, Zheng Yang Lee1, Chee Hong Leong1, Faris B. Norizan1, Sathiavani A. Arikrishnan2, Yin Sim Tor2, May Lee Low3 and Chew Hee Ng3 1 School of Pharmacy, Taylor's University, Faculty of Health and Medical Sciences, Malaysia 2 School of Biosciences, Taylor's University, Faculty of Health and Medical Sciences, Malaysia 3 International Medical University, Department of Pharmaceutical Chemistry, School of Pharmacy, Malaysia Background The use of copper complexes for cancer treatment has been widely explored as cancer cells are reported to take up greater amounts of copper than normal cells. Our previous study had successfully synthesised and characterised the Cu(phen)(L-tyr)Cl]·3H2O copper complex. Nevertheless, the mode of cell death induced by this copper complex against cancer cells remains unclear. Therefore, the current study investigated the mode of cell death induced by Cu(phen)(L-tyr)Cl]·3H2O against human breast and colon cancer cell lines. Methods The inhibitory and morphological changes induced by Cu(phen)(L-tyr)Cl]·3H2O against human breast (MDA-MB-231) and colon (HT-29) cancer cell lines were determined by the MTT assay and inverted light microscopy, respectively. Induction of cell cycle arrest and apoptosis were determined by flow cytometry analysis. Results The growth of cancer cell lines was inhibited by Cu(phen)(L-tyr)Cl]·3H2O in a dose- dependent manner with IC50 value of 3.5 µM against these two cancer cell lines. The copper complex was 9 and 1.5 folds more potent than cisplatin in inhibiting the growth of HT-29 colon and MDA-MB-231 breast cancer cells, respectively. It was found that Cu(phen)(L-tyr)Cl]·3H2O induced S phase cell cycle arrest on HT-29 colon and MDA-MB-231 breast cancer cells. Characteristics of apoptosis such as cellular shrinkage, membrane blebbing and apoptotic bodies were seen under inverted light microscope, indicating that Cu(phen)(L-tyr)Cl]·3H2O induced apoptosis in the cells. The observation was further ascertained using Annexin-V/PI flow cytometry analysis. Conclusion Our present study provided evidence regarding the anticancer effects and underlying mechanisms of Cu(phen)(L-tyr)Cl]·3H2O against human breast and colon cancer cells. These findings shed new light on the potential application of Cu(phen)(L-tyr)Cl]·3H2O as anticancer agent. Keywords: Copper Complex, Colon Cancer, breast cancer, Apoptosis, cell cycle arrest Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Cancer Citation: Foo J, Teo X, Lee Z, Leong C, Norizan FB, Arikrishnan SA, Tor Y, Low M and Ng C (2019). Ternary copper (II) complex induced cell cycle arrest and apoptosis in human breast (MDA-MB-231) and colon (HT-29) cancer cells. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00135 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Nov 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Jhi Biau Foo, School of Pharmacy, Taylor's University, Faculty of Health and Medical Sciences, Subang Jaya, Selangor Darul Ehsan, 47500, Malaysia, foojhibiau@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jhi Biau Foo Xian Wei Teo Zheng Yang Lee Chee Hong Leong Faris B Norizan Sathiavani A Arikrishnan Yin Sim Tor May Lee Low Chew Hee Ng Google Jhi Biau Foo Xian Wei Teo Zheng Yang Lee Chee Hong Leong Faris B Norizan Sathiavani A Arikrishnan Yin Sim Tor May Lee Low Chew Hee Ng Google Scholar Jhi Biau Foo Xian Wei Teo Zheng Yang Lee Chee Hong Leong Faris B Norizan Sathiavani A Arikrishnan Yin Sim Tor May Lee Low Chew Hee Ng PubMed Jhi Biau Foo Xian Wei Teo Zheng Yang Lee Chee Hong Leong Faris B Norizan Sathiavani A Arikrishnan Yin Sim Tor May Lee Low Chew Hee Ng Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Simple and mixed complexes of copper(II) with 8-hydroxyquinoline derivatives and amino acids: Characterization in solution and potential biological implications

Copper(II) complexes with 8-hydroxyquinoline (8-HQ) and two 8-HQ derivatives, namely clioquinol (CQ) and 5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol (PBT2), were investigated in organic and, where feasible, in aqueous solutions. This class of compounds is of particular interest in neurological disorders since they may act as metal-protein attenuating compounds and may help redistributing metal ions and restoring intracellular metal reserves, which are often perturbed in neurological patients. Several techniques, like potentiometry, UV–Vis absorption, electron paramagnetic resonance (EPR), cyclic voltammetry and electrospray ionisation-mass spectrometry (ESI-MS), were used to obtain information on both the formation of copper(II) complexes in solution as well as on the structure of their species. Multi-wavelength treatment of UV–Vis data clearly indicated the formation of both [Cu(PBT2)]+ and [Cu(PBT2)2] species; the speciation was also supported by ESI-MS data. The EPR results showed that the mono- and bis-copper(II) complexes with PBT2 have square-based pyramidal structures while the bis-copper (II) complexes with CQ or 8-HQ have square-planar o pseudo-octahedral geometries. The formation of copper(II) ternary complexes with 8-HQ, CQ and PBT2 and some selected neurotransmitters (glycine, glutamate and histidine) is also reported. Except for the copper(II) ternary complex with PBT2 and His, almost all ternary complexes have molecular geometries, which are not different from those of the bis-complexes. Interestingly the ternary copper(II) complexes, containing CQ, 8-HQ and PBT2 and glycine, glutamate or histidine turned out to be more soluble in aqueous solution than their binary complexes with parent 8-HQ derivatives; the copper(II) complexes can also be reduced more easily than their parent bis-complexes.

Copper(II) and silver(I) complexes with sulfamethizole: synthesis, spectroscopic characterization, ESI-QTOF mass spectrometric analysis, crystal structure and antibacterial activities

A ternary copper(II) complex with sulfamethizole (SMZ, C9H10N4O2S2) and 1,10-phenantroline (phen), [Cu(SMZ)2(phen)], and a silver(I) complex with sulfamethizole, Ag-SMZ, are presented. Elemental analyses indicate a 2:1:1 SMZ/copper/phen composition for the [Cu(SMZ)2(phen)] complex and a 1:1 silver/SMZ composition for the Ag-SMZ complex. Mass spectrometric analyses permitted identifying the [Cu(SMZ)2(phen)+H]+ and [Ag(SMZ)+H]+ ions at m/z 782.0297 and m/z 378.9371, respectively, confirming the proposed compositions. Theoretical isotopic patterns match with the experimental ones for the copper and silver complexes. 1H and {15N,1H} HMBC nuclear magnetic resonance (NMR), and infrared (IR) spectroscopic measurements evidence the coordination of sulfamethizole to silver(I) by the SO2-N group, and indicate the participation of the 5-membered heterocyclic ring 5-methyl-1,3,4-thiadiazole in coordination. The [Cu(SMZ)2(phen)] crystal structure was determined by single crystal X-ray diffractometry, attesting the N-coordination of sulfamethizole to copper(II) by the nitrogen of the 5-methyl-1,3,4-thiadiazole heterocyclic ring. Electronic paramagnetic resonance (EPR) indicates a square pyramidal geometry around the copper(II) ion for the [Cu(SMZ)2(phen)] complex. Biological studies showed the antibacterial activity of the Ag-SMZ and [Cu(SMZ)2(phen)] complexes over Gram-positive and Gram-negative bacteria. Both complexes have shown to be more active against Gram-negative Pseudomonas aeruginosa ATCC bacterial strain, with minimum inhibitory concentration (MIC) values of 0.41 mmol L−1 for the silver(I) complex and 1.60 mmol L−1 for the copper(II) complex.

Fluorescence and electron paramagnetic resonance studies of norfloxacin and N-donor mixed-ligand ternary copper(II) complexes: Stability and interaction with SDS micelles

The stability of ternary copper(II) complexes of a heterocyclic ligand, L (L being 2,2′-bipyridine (bipy) or 1,10-phenanthroline (phen)) and the fluorescent antibacterial agent norfloxacin (NFX) as the second ligand was studied at pH7.4 and different ionic strengths. Fluorescence quenching upon titration of NFX with the binary complexes allowed to obtain stability constants for NFX binding, Kb, as a function of ionic strength. The Kb values vary by more than two orders of magnitude when buffer concentration varies from 0.5 to 100mM. It was observed that previously synthesized ternary complexes dissociate in buffer according with the obtained stability constants. This shows that equimolar solutions of NFX and binary complexes are equivalent to solutions of synthesized ternary complexes. The interaction of the ternary copper complexes with anionic SDS (sodium dodecyl sulfate) micelles was studied by fluorescence and electron paramagnetic resonance (EPR). Titration of NFX-loaded SDS micelles with the complexes Cu:L allowed to determine the stability constants inside the micelles. Fluorescence quenching demonstrated that SDS micelles increase the stability constants by factors around 50. EPR spectra gave details of the copper(II) local environment, and demonstrated that the structure of the ternary complexes inside SDS micelles is different from that in buffer. Mononuclear ternary complexes formed inside the micelles, while in buffer most ternary complexes are binuclear. The results show that anionic membrane interfaces increase formation of copper fluoroquinolone complexes, which can influence bioavailability, membrane diffusion, and mechanism of action of the antibiotics.

Synthesis, and structural characterization of mixed ligand copper(II) complexes of N,N,N′,N'-tetramethylethylenediamine incorporating carboxylates

Two ternary copper(II) complexes of N,N,N′,N'-tetramethylethylenediamine (tmen = C6H16N2) with benzoic acid and p-aminobenzoic acid, having the formula [Cu(tmen)(BA)2(H2O)2] (1), and [Cu(tmen)(pABA)2]. 1/2 CH3OH (2) {(Where BA1− = benzoate1− (C6H5CO21−), pABA1− = p-aminobenzoate1- (p-H2NC6H5CO21−)} have been prepared and characterized by elemental combustion analysis, Uv–Visible spectroscopy, FT-IR spectroscopy, thermal, and single crystal X-ray diffraction analyses. The complex 1 is a monomer with distorted octahedral geometry. In its CuN2O4 chromophore, the Cu(II) centre is coordinated by two N atoms of a symmetrically chelating tmen ligand, by two carboxylate-O atoms from two monodentate benzoate1− anions, and by two apical aqua-O atoms, which define the distorted octahedral structure. The complex 2 is a monomer with a distorted square planar coordination geometry. In CuN2O2 chromophore, tmen is coordinated to Cu(II) ion in a chelating bidentate fashion, while the two p-aminobenzoate1- anions coordinate to Cu(II) centre through their carboxylate-O atoms in a monodentate manner, forming a square planar structure. The observed difference between asymmetric ѵas(OCO) and symmetric ѵs(OCO) stretching IR vibrations of the carboxylate moieties for 1 and 2 is 220 cm−1 and 232 cm−1, respectively, which suggests monodentate coordination mode (Δν OCO>200) of the carboxylate groups to Cu(II) ion. Thermogravimetric studies of 1 indicates removal of two water molecules at 171 °C, elimination of a tmen upto 529 °C and of two benzoate groups upto 931 °C. In tga curve of 2, methanol is lost upto 212 °C, while tmen is lost from 212 to 993 °C. The antibacterial activities of these new compounds against various bacterial strains were also investigated.

Binary and ternary copper(II) complexes of a new Schiff base ligand derived from 4-acetyl-5,6-diphenyl-3(2H)-pyridazinone: Synthesis, spectral, thermal, antimicrobial and antitumor studies

A new Schiff base ligand was synthesized by the reaction of 4-acetyl-5,6-diphenyl-3(2H)-pyridazinone with ethylenediamine. A series of binary copper(II) Schiff base complexes have been synthesized by using various copper(II) salts; AcO−, NO3−, ClO4−, Cl− and Br−. Ternary complexes were synthesized by using auxiliary ligands (L′) [N,O-donor; 8-hydroxyquinoline and glycine or N,N-donor; 1,10-phenanthroline, bipyridyl and 2-aminopyridine]. The structures of the Schiff base and its complexes were characterized by elemental and thermal analyses, IR, electronic, mass, 1H NMR and ESR spectra in addition to conductivity and magnetic susceptibility measurements. The obtained complexes include neutral binuclear complexes as well as neutral and cationic mononuclear complexes according to the anion used and the experimental conditions. The ESR spin Hamiltonian parameters of some complexes were calculated and discussed. The metal complexes exhibited octahedral and square planar geometrical arrangements depending on the nature of the anion. Kinetic parameters (Ea, A, ΔH, ΔS and ΔG) of the thermal decomposition stages were evaluated using Coats–Redfern equations. The antimicrobial activity of the Schiff base and its complexes was screened against Gram–positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram–negative bacteria (Salmonella typhimurium and Escherichia coli), yeast (Candida albicans) and fungus (Aspergillus fumigatus). The antitumor activity of the Schiff base and some of its Cu(II) complexes was investigated against HepG-2 cell line.

Synthesis, characterisation, DNA binding/cleavage, anticancer and antimicrobial activity of ternary copper(II) complexes

Ternary copper(II) complexes [Cu(L-Ser)(HB)(U)](ClO4) (1 and 2) where L-Ser = L-Serine, U = Urea, HB is a N,N-donor heterocyclic bases, viz. 1,10-phenanthroline (phen) (1), 2, 2’- bipyridine (bpy) (2), are synthesized, characterized, and their DNA binding, cleavage and antimicrobial activities are studied. The one-electron paramagnetic complexes display a d-d band near 600 nm in water. Binding interactions of the complexes with calf thymus (CT) DNA have been investigated by absorption, emission, viscosity, and cyclic voltammetry studies. The complexes cleave the supercoiled DNA (pBR 322) to its nicked circular form in the presence of gallic acid at appropriate complexes concentration. The phen complex (1) displays significant binding propensity to the CT DNA. The bpy complex (2) does not show any significant binding to the DNA and hence poor cleavage efficiency.

Synthesis, crystal structure, stability studies, DNA/albumin interactions, and antimicrobial activities of two Cu(II) complexes with amino acids and 5-nitro-1,10-phenanthroline

One-dimensional (1-D) coordination polymer and mononuclear copper(II) complexes, ([Cu(nphen)(asn)]ClO4)n (1) and [Cu(nphen)(gln)(H2O)]ClO4·H2O (2) (nphen = 5-nitro-110-phenanthroline, asn = asparagine, gln = glutamine), have been synthesized and characterized by IR spectroscopy, ESI-MS, CHN analysis, and single-crystal X-ray diffraction. These binary and ternary complexes of copper(II) with nphen, asn, and gln have been investigated using potentiometric methods in 0.1 M KCl aqueous ionic media at 298.2 K. The protonation constants of the ligands and the stability constants of 1 and 2 have been calculated from the potentiometric data using the “BEST” software package. The potentiometric results have been analyzed using the “SPE” software package, and the distribution curves for the copper-containing species have been determined for the ternary systems. The CT-DNA-binding properties of these complexes have been investigated by thermal denaturation measurements and both absorption and emission spectroscopy. Further, the interaction of these complexes with bovine serum albumin (BSA) and human serum albumin (HSA) has been investigated using absorption and emission spectroscopy. The thermodynamic parameters, free energy change (ΔG), enthalpy change (ΔH), and entropy change (ΔS) were calculated by the van’t Hoff equation and discussed. The distances between the serum albumins and 1 and 2 have been obtained according to fluorescence resonance energy transfer (FRET). Conformational changes of serum albumins have been observed from synchronous fluorescence technique. The antimicrobial activity of the complexes has also been tested on some bacteria. The effect of different amino acids on the copper(II) complexes are discussed.

Formation studies of binary and ternary complexes of copper(II) with an oxazol derivative of nicotinic acid and some amino acids

Abstract Binary and ternary complexes of copper(II) with the 2-(benzo[d]oxazol-2-yl)nicotinic acid (Ligand HL) and the amino acids Glycine (HGly, HB), Proline (HPro, HB), α-Alanine (Hα-Ala, HB), β-Alanine (Hβ-Ala, HB) were studied in aqueous solution at 25 °C, using 1.0 mol · dm− 3 KNO3 as the ionic medium. The types of complexes formed and their overall stability constants were established on the basis of the computer analysis of the potentiometric data, using a version of the program LETAGROP. It was inferred that the aromatic oxazol Ligand L− 1 acts as a primary ligand in the ternary complexes, while the oxygen and nitrogen donor-containing amino acids are the secondary ligands. The analysis showed the formation of five complexes: [Cu(L)(HB)]+, Cu(L)(B), [Cu(L)(B)(OH)]−, [Cu(L)2(B)]− and [Cu(L)(B)2]− in the Cu(II)-L−-Gly and Cu(II)-L− -βAla systems, for the Cu(II)-L−-Pro system, the complexes [Cu(L)(HB)]+, Cu(L)(B), [Cu(L)(B)(OH)]− and [Cu(L)(B)2]− were detected and, finally, in the Cu(II)- L− - αAla system, only the complexes [Cu(L)(HB)]+, Cu(L)(B) and [Cu(L)(B)(OH)]− were observed. The concentration distributions of various species formed in aqueous solution were also evaluated as a function of pH.

Syntheses and Structures of Monomeric and Dimeric Ternary Complexes of Copper(II) with 2,2′‐Bipyridyl and Carboxylate Ligands

The syntheses and crystal structures of Cu(C10H8N2)(C9H7O2)(H2O) (1) and [Cu2(C10H8N2)2(C7H6NO2)3(C7H7NO2)]·Cl·3H2O (2) are described [C10H8N2 = 2,2′‐bipyridine (bipy), C9H7O2– = cinnamate anion (cinn–), C7H6NO2– = p‐amino benzoate anion (paba–), and C7H7NO2 = p‐amino benzoic acid (Hpaba)]. Complex 1 [triclinic, space group P1 (no. 2), a = 12.0357 (7) Å, b = 13.8799 (8) Å, c = 16.3225 (9) Å, α = 84.916 (3)°, β = 88.551 (3)°, γ = 67.877 (3)°, V = 2516.0 (2) Å3, Z = 4] contains two molecules in the asymmetric unit: both feature a distorted square‐pyramidal CuN2O3 chromophore arising from the coordination of a bidentate bipy ligand, two monodentate cinn– anions, and a water molecule to the metal ion. The cation in complex 2 [orthorhombic, space group P212121 (no. 19), a = 13.5061 (10) Å, b = 18.1441 (11) Å, c = 18.9671 (13) Å, V = 4648.1 (5) Å3, Z = 4] is dimeric with square pyramidal CuN2O3 and CuN3O2 metal coordination polyhedra: each metal ion is coordinated by a bidentate bipy ligand and two bridging paba– anions; the apical coordination site of one is occupied by an O‐bonded paba– anion and the other by an N‐bonded Hpaba neutral molecule. The cation in 2 is isomeric with the previously reported [Cu2(C10H8N2)2(C7H6NO2)2(C7H7NO2)2]2+ cation, in which both apical Hpaba molecules are N‐bonded to their metal ions.

Ternary and binary copper(II) complexes: synthesis, characterization, ROS-inductive, proteasome inhibitory, and anticancer properties

Three ternary copper(II) complexes, [Cu(phen)(L-phe)Cl]·2H2O, [Cu(phen)(L-leu)Cl]·4½H2O, and [Cu(phen)(L-tyr)Cl]·3H2O, and four binary copper(II) complexes, [Cu(phen)Cl2], Cu(L-phe)2·½H2O, Cu(L-leu)2·½H2O, and Cu(L-tyr)2·H2O (where phen = 110-phenanthroline, L-phe = L-phenylalanine, L-tyr = L-tyrosine, L-leu = L-leucine and Cl- = chloride), were synthesized and characterized by elemental analysis, spectroscopic techniques (FTIR, UV–visible, fluorescence spectroscopy), magnetic susceptibility, molar conductivity, and lipophilicity measurement. X-ray diffraction determination of a single crystal of [Cu(phen)(L-tyr)Cl] showed two independent molecules in the asymmetric unit, each with the same distorted square pyramidal geometry about copper(II). p-Nitrosodimethylaniline assay revealed that the three ternary complexes were better inducers of reactive oxygen species over time than binary complexes, CuCl2, and free ligands. All the copper(II) complexes in this series inhibited the three proteolytic activities in the order Trypsin-like > Caspase-like > Chymotrypsin-like. In terms of anticancer properties, the copper(II)-phen complexes had GI50 values of less than 4 μM against MCF-7, HepG2, CNE1 and A549 cancer cell lines, more potent than cisplatin.

Synthesis, crystal structures and biological evaluation of three ternary copper(II) complexes with fluorinated anthranilic acid derivatives

Three ternary copper(II) complexes [Cu(L1)(phen)] (1), [Cu(L2)(phen)] (2), and [Cu(L3)(phen)]·2H2O (3) (L1 = 4-fluoro-2-(picolinamido)benzoic acid, L2 = 4,5-difluoro-2-(picolinamido)benzoic acid, L3 = 4,5-difluoro-2-((2-hydroxybenzylidene)amino)benzoic acid, phen = 1,10-phenanthroline) have been synthesized and characterized by physicochemical and spectroscopic methods. In addition, X-ray crystallography showed that the Cu atoms in each of the complexes are five-coordinate, adopting distorted square pyramidal or trigonal bipyramidal geometries. The interactions of the complexes with calf-thymus DNA were investigated by UV absorption, fluorescence spectroscopy and viscosity measurements. In addition, the complexes were screened for in vitro cytotoxicity against A549 (human pulmonary carcinoma cells), Jurkat (human T lymphocyte cell line) and HepG-2 (human liver hepatocellular carcinoma cells); these experiments showed that complex 3 exhibited the most effective cytotoxicities (IC50 = 1.224–7.099 µM). Antibacterial studies revealed that complex 3 also exhibited highest activity, consistent with the DNA binding affinities.

Molecular docking, free radical scavenging, and DNA interaction studies of drug-based coordination compounds

Five-coordinated distorted square pyramidal ternary copper(II) complexes of ciprofloxacin and derivatives of phenanthroline (2,9-dimethyl-1,10-phenanthroline, 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, 4,5-diazafluoren-9-one, 1,10-phenanthroline-5,6-dione, and 5-nitro-1,10-phenanthroline) with one chlorine at axial position were prepared and were characterized well. Considerable raise in antimicrobial activity was observed because chelation favors the transfer of metal ion to cross the cell membrane barrier, which interferes in normal cell process. Complexes were found to exhibit intercalative mode of binding with DNA with an extent of K b values ranging from 0.725 to 1.827 × 105 M−1. The DNA-binding property of all the complexes have been also examined theoretically using molecular docking study and recommends intercalation binding mode between all complexes and nucleotide base pairs of HS DNA. DNA scissoring activity of complexes was found to be greater than ciprofloxacin by 8 % and more, also the synthesized complexes were found to be potent oxygen radical scavenger with effective concentration ranging of 0.7583–1.6865 µM.

Design and characterization of highly in vitro antitumor active ternary copper(II) complexes containing 2′-hydroxychalcone ligands

A series of innovative copper(II) complexes of the general composition [Cu(Ln)(phen)]NO3 (1–8; phen=1,10-phenanthroline), involving 2′-hydroxychalcone {(E)-1-(2′-hydroxyphenyl)-3-phenylprop-2-en-1-one} derivatives (HLn) was synthesized, thoroughly characterized and screened for in vitro cytotoxicity against a panel of ten human cancer cell lines. The most promising results were achieved for complex 2 with the best IC50 value of 1.1±0.7μM (against A2780 cell line). The toxicity testing on a primary culture of human hepatocytes (HH) revealed that complex 2 is the least toxic from the whole series with the IC50 value of 63.7μM. The complexes were shown to be able to efficaciously cleave pUC19 plasmid DNA as well as intercalate into calf thymus DNA with the same affinity and efficacy as ethidium bromide and interact by the ligand exchange mechanism with l-cysteine at physiological concentration levels.