A novel phenolato-, chlorido- and end-on azido-cobridged tetranuclear copper(II) complex, Cu
4
(daemp)
2
Cl
2
(μ-Cl)
2
(μ
1,1
-N
3
)
2
(MeOH)
2
(Hdaemp = ...2-(2-dimethylaminoethylimino)methyl-4-methylphenol), was prepared and characterized by elemental analyses, IR and UV-Vis spectra, and single crystal X-ray diffraction study. The Schiff base ligands coordinate to the Cu atoms through phenolate O, imino N and amino N atoms. The adjacent Cu···Cu distances are 3.169(2) and 3.063(2) Å. Each Cu atom is in a square pyramidal coordination. The azido ligands link two Cu atoms with end-on bridging mode. There are two coordination modes for the Cl ligands, viz. terminal and bridging. In the crystal structure, the complex molecules are stack along the b axis.
In this study, the interaction between human serum albumin (HSA) and a copper complex of carmoisine dye; Cu(carmoisine)2(H2O)2, was studied in vitro using multi‐spectroscopic methods. It was found ...that the intrinsic fluorescence of HSA was quenched by the addition of the Cu(carmoisine)2(H2O)2 complex and the quenching mechanism was considered as static quenching by formation of a Cu(carmoisine)2(H2O)2–HSA complex. The binding constant was about 104 M−1 at room temperature. The values of the calculated thermodynamic parameters (ΔH < 0 and ΔS > 0) suggested that both hydrogen bonds and the hydrophobic interactions were involved in the binding process. The site marker competitive experiments revealed that the binding of Cu(carmoisine)2(H2O)2 to HSA primarily occurred in subdomain IIIA (site II) of HSA. The results of circular dichroism (CD) and UV–vis spectroscopy showed that the micro‐environment of amino acid residues and the conformation of HSA were changed after addition of the Cu(carmoisine)2(H2O)2 complex. Finally, the binding of the Cu(carmoisine)2(H2O)2 complex to HSA was modelled by a molecular docking method. Excellent agreement was obtained between the experimental and theoretical results with respect to the binding forces and binding constant.
Emerging infections of unknown origin and increasing bacterial resistance against available antibiotics necessitate the development of different antimicrobial agents with unconventional mechanisms of ...action. A promising strategy to meet this need may be found by combining polymeric scaffolds with transition metals, e.g., by decorating polyacrylate-based microgels with Cu(II) complexes. A series of structure–activity relationship studies using broth microdilution assays with such materials and Staphylococcus aureus concluded that the antimicrobial activity of microgels can be tailored during their synthesis by choice of co-monomers, by design of the binding strength between Cu(II) ions and backbone ligands, and by selection of the counter ions for coordination to the metal complexes. A microgel Cu2LP(EG) (L = VBbsdpo) with an optimized minimal inhibitory concentration of 0.39 ± 0.03 μg/mL is thereby derived and synthesized from 60 mol % of cross-linking ethylene glycol dimethacrylate, 40 mol % butyl acrylate, 0.5 mol % VBbsdpo ligand with 1 mol % Cu(II) ions, and 5 mol % ethylene glycol as counter ions. The antimicrobial activity of the microgel has a lifetime of over 18 months at ambient temperature. Bactericidal activity of the same microgel is observed by replating assays in less than 15 min when exposing S. aureus to microgel concentrations of 1.5-fold of its minimum inhibitory concentration (MIC) value or higher. Furthermore, spectrophotometric evaluations at 260 nm revealed time- and concentration-dependent release of intracellular bacterial components after interactions with the microgel indicating irreversible damage to the bacterial cell membrane as a possible mechanism of activity. Preliminary results indicate that the selected microgels are not cytotoxic toward human dermal fibroblasts at MIC value concentrations for over 20 h.
A mononuclear Cu(II) complex, Cu(FA)
2
(NO
3
)
2
, in which FA is ferulic acid ((E)-3-(4-hydroxy-3-methoxy-phenyl)prop-2-enoic acid), was synthesized and characterized by spectroscopic methods. The ...main structures of the ligand and its complexes with Cu
2+
were optimized by QM calculations. The calculations on the structures of the Cu(FA)
2
(NO
3
)
2
complexes forms and the intercalating with DNA profile were undertaken by UHF/PM6 and MMFF94 methods, respectively. In vitro studies (UV-vis spectroscopy, emission titration, circular dichroism techniques, and viscometry) under physiological conditions (Tris-HCl buffer solutions, pH 7.4) showed that the complex interacts with calf-thymus DNA (ct-DNA) via an intercalative binding mode. The thermodynamic parameters, enthalpy change (ΔH), and entropy change (ΔS) showed that the acting forces between Cu(II) complex and ct-DNA mainly included van der Waals interactions and hydrogen bonds. Methylene blue (MB) displacement studies revealed that Cu(II) complex can substitute MB probe in the MB-DNA complex which was indicative of intercalative binding. The theoretical data confirm the experimental results with respect to the mechanism of binding.
The coordination compound of the antihypertensive ligand irbesartan (irb) with copper(II) (CuIrb) was synthesized and characterized by FTIR, FT-Raman, UV–visible, reflectance and EPR spectroscopies. ...Experimental evidence allowed the implementation of structural and vibrational studies by theoretical calculations made in the light of the density functional theory (DFT). This compound was designed to induce structural modifications on the ligand. No antioxidant effects were displayed by both compounds, though CuIrb behaved as a weak 1,1-diphenyl-2-picrylhydrazyl radical (DPPH
·
) scavenger (IC
50
= 425 μM). The measurements of the contractile capacity on human mesangial cell lines showed that CuIrb improved the antihypertensive effects of the parent medication. In vitro cell growth inhibition against prostate cancer cell lines (LNCaP and DU 145) was measured for CuIrb, irbesartan and copper(II). These cell lines have been selected since the angiotensin II type 1 (AT1) receptor (that was blocked by the angiotensin receptor blockers, ARB) has been identified in them. The complex exerted anticancer behavior (at 100 μM) improving the activity of the ligand. Flow cytometry determinations were used to determine late apoptotic mechanisms of cell death.
Graphical Abstract
Experimental and DFT characterization of an irbesartan copper(II) complex has been performed. The complex exhibits low scavenging activity against DPPH
·
and significant growth inhibition of LNCaP and DU 145 prostate cancer cell lines. Flow cytometry determinations were used to determine late apoptotic mechanisms of cell death. This compound improved the antihypertensive effect of irbesartan. This effect was observed earlier for the mononuclear Cu–candesartan complex, but not in structurally modified sartans forming dinuclear or octanuclear Cu–sartan compounds.
The Cu(II) complex of a berberine carboxylate was synthesized and found to exhibit potent DNA-cleaving activity under physiological conditions.
9-O-(4-carboxybenzyl)berberine (CBB) 1 was synthesized ...from the reaction of berberrubine with methyl 4-(bromomethyl)benzoate and subsequent hydrolysis. Its Cu(II) complex 2 was prepared from the reaction with Cu(NO3)2·3H2O, and established as Cu(CBB)2(NO3)2·2H2O by means of 1H NMR, UV, IR, elemental analysis and TGA measurements. Agarose gel electrophoresis study on the cleavage of plasmid pBR322 DNA indicated that complex 2 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanistic pathway involving the formation of singlet oxygen as the reactive species. Kinetic assay afforded the maximal first-order rate constant kmax of 2.41h−1 and Michaelis constant KM of 2.64mM, respectively, representing ca. 108-fold acceleration in the cleavage. This catalytic efficacy is attributed to the Cu(II)-assisted formation of dimeric species, in which the two berberine subunits cooperatively bind to DNA, whereas the carboxylate-coordinated Cu(II) moiety functions as the cleavage-active center.
DNA-binding properties of novel copper(II) complex Cu(
l-Phe)(TATP)(H
2O)
+, where
l-Phe
=
l-phenylalaninate and TATP
=
1,4,8,9-tetra-aza-triphenylene are investigated using electronic absorption ...spectroscopy, fluorescence spectroscopy, voltammetry and viscosity measurement. It is found that the presence of calf thymus DNA results in a hypochromism and red shift in the electronic absorption, a quenching effect on fluorescence nature of ethidium bromide–DNA system, an enhanced response on voltammograms of Co(phen)
3
3+/2+–DNA system, and an obvious change in viscosity of DNA. From absorption titration, fluorescence analysis and voltammetric measurement, the binding constant of the complex with DNA is calculated. The latter two methods reveal the stronger binding of Cu(
l-Phe)(TATP)(H
2O)
+ complex to double strand DNA by the moderate intercalation than Co(phen)
3
3+. Such a binding induces the cleavage of plasmid pBR322 DNA in the presence of H
2O
2.
To develop chiral anticancer drug candidates for molecular target DNA, the synthesis and characterization of a novel enantiomerically pure copper(II) complex
Cu
1
Cl
2
(
2
) of an optically pure ...ligand
N
-(pyridin-2-ylmethylene) dehydroabietylamine (
1
) was carried out. The coordination geometry of the copper center is a distorted square-planar arrangement. The interactions of
1
and
2
with salmon sperm DNA were investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. All the results reveal that
1
and
2
interacted with DNA through intercalation and
2
exhibited a higher DNA binding ability. Further,
1
and
2
could cleave supercoiled pBR322 DNA by single strand and
2
displayed stronger cleavage ability in the presence of ascorbic acid. In vitro cytotoxicity of
1
and
2
against HeLa, SiHa, HepG-2 and A431 cancer cell lines was studied using CCK-8 assay. The results indicate that
2
had a superior cytotoxicity than
1
and the widely used drug cisplatin under identical conditions. Flow cytometry analysis demonstrates
2
produced death of HeLa cancer cells through an apoptotic pathway. Cell cycle analysis shows that
2
mainly arrested HeLa cells at the S phase.
Graphical abstract
A novel enantiomerically pure copper(II) complex
Cu
1
Cl
2
(
2
) of an optically pure ligand
N
-(pyridin-2-ylmethylene) dehydroabietylamine (
1
), based on natural product rosin has been synthesized.
2
has the potential to act as effective anticancer drug.
