Aqueous Solution Equilibria and Spectral Features of Copper Complexes with Tripeptides Containing Glycine or Sarcosine and Leucine or Phenylalanine

Copper(II) complexes of glycyl-L-leucyl-L-histidine (GLH), sarcosyl-L-leucyl-L-histidine (Sar-LH), glycyl-L-phenylalanyl-L-histidine (GFH) and sarcosyl-L-phenylalanyl-L-histidine (Sar-FH) have potential anti-inflammatory activity, which can help to alleviate the symptoms associated with rheumatoid arthritis (RA). From pH 2–11, the MLH, ML, MLH-1 and MLH-2 species formed. The combination of species for each ligand was different, except at the physiological pH, where CuLH-2 predominated for all ligands. The prevalence of this species was supported by EPR, ultraviolet-visible spectrophotometry, and mass spectrometry, which suggested a square planar CuN4 coordination. All ligands have the same basicity for the amine and imidazole-N, but the methyl group of sarcosine decreased the stability of MLH and MLH-2 by 0.1–0.34 and 0.46–0.48 log units, respectively. Phenylalanine increased the stability of MLH and MLH-2 by 0.05–0.29 and 1.19–1.21 log units, respectively. For all ligands, 1H NMR identified two coordination modes for MLH, where copper(II) coordinates via the amine-N and neighboring carbonyl-O, as well as via the imidazole-N and carboxyl-O. EPR spectroscopy identified the MLH, ML and MLH-2 species for Cu-Sar-LH and suggested a CuN2O2 chromophore for ML. DFT calculations with water as a solvent confirmed the proposed coordination modes of each species at the B3LYP level combined with 6-31++G**.

Efficient dye-sensitized solar cells based on bioinspired copper redox mediators by tailoring counterions

In recent years, copper(II/I) complexes have attracted growing interest as redox mediators in dye-sensitized solar cells. Here, we report a new class of copper complexes bearing a bis(2-pyridylmethyl)-1,2-ethanedithiol ligand, coded...

In Silico Inhibitability of Copper Carbenes and Silylenes against Rhizoctonia solani and Magnaporthe oryzae

Copper lighter tetrylenes are promising for inhibition towards Rhizoctonia solani-based protein PDB-4G9M and Magnaporthe oryzae-based PDB-6JBR in rice. Quantum properties of four hypothetic copper complexes of carbenes and silylenes (Cu-NHC1, Cu-NHC2, Cu-NHSi1, and Cu-NHSi2) were examined using the density functional theory. Their inhibitability towards the targeted proteins was evaluated using molecular docking simulation. Quantum analysis predicts the stability of the investigated complexes and thus their practical existability and practicable synthesisability. Their electronic configurations are justified as highly conducive to intermolecular interaction. Regarding ligand-protein as carbenes/silylenes-4G9M inhibitory structures, the stability is estimated in the order [Cu-NHC2]-4G9M (DS −12.9 kcal⋅mol−1) > [Cu-NHSi1]-4G9M (DS −11.8 kcal⋅mol−1) = [Cu-NHSi2]-4G9M (DS −11.7 kcal⋅mol−1) > [Cu-NHC1]-4G9M (DS –11.4 kcal⋅mol−1). In contrast, the corresponding order for the carbenes/silylenes-6JBR systems is [Cu-NHSi2]-6JBR (DS –13.4 kcal⋅mol−1) > [Cu-NHC2]-6JBR (DS −13.0 kcal⋅mol−1) = [Cu-NHSi1]-6JBR (DS −12.6 kcal⋅mol−1) > [Cu-NHC1]-6JBR (DS −12.3 kcal⋅mol−1). In theory, this study suggests a potentiality of copper lighter tetrylenes and their derivatives against the infection of fungi Rhizoctonia solani and Magnaporthe oryzae, thus encouraging attempts for experimental developments.

Copper(II) Phenanthroline-Based Complexes as Potential AntiCancer Drugs: A Walkthrough on the Mechanisms of Action

Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.

Terminal and Internal Alkyne Complexes and Azide-Alkyne Cycloaddition Chemistry of Copper(I) Supported by a Fluorinated Bis(pyrazolyl)borate

Copper plays an important role in alkyne coordination chemistry and transformations. This report describes the isolation and full characterization of a thermally stable, copper(I) acetylene complex using a highly fluorinated bis(pyrazolyl)borate ligand support. Details of the related copper(I) complex of HCºCSiMe3 are also reported. They are three-coordinate copper complexes featuring η2-bound alkynes. Raman data show significant red-shifts in CºC stretch of [H2B(3,5-(CF3)2Pz)2]Cu(HCºCH) and [H2B(3,5-(CF3)2Pz)2]Cu(HCºCSiMe3) relative to those of the corresponding alkynes. Computational analysis using DFT indicates that the Cu(I) alkyne interaction in these molecules is primarily of the electrostatic character. The π-backbonding is the larger component of the orbital contribution to the interaction. The dinuclear complexes such as Cu2(μ-[3,5-(CF3)2Pz])2(HCºCH)2 display similar Cu-alkyne bonding features. The mononuclear [H2B(3,5-(CF3)2Pz)2]Cu(NCMe) complex catalyzes [3+2] cycloadditions between tolyl azide and a variety of alkynes including acetylene. It is comparatively less effective than the related trinuclear copper catalyst {μ-[3,5-(CF3)2Pz]Cu}3 involving bridging pyrazolates.

Hybrid Bis-Histidine Phenanthroline-Based Ligands to Lessen Aβ-Bound Cu ROS Production: An Illustration of Cu(I) Significance

We here report the synthesis of three new hybrid ligands built around the phenanthroline scaffold and encompassing two histidine-like moieties: phenHH, phenHGH and H’phenH’, where H correspond to histidine and H’ to histamine. These ligands were designed to capture Cu(I/II) from the amyloid-β peptide and to prevent the formation of reactive oxygen species produced by amyloid-β bound copper in presence of physiological reductant (e.g., ascorbate) and dioxygen. The amyloid-β peptide is a well-known key player in Alzheimer’s disease, a debilitating and devasting neurological disorder the mankind has to fight against. The Cu-Aβ complex does participate in the oxidative stress observed in the disease, due to the redox ability of the Cu(I/II) ions. The complete characterization of the copper complexes made with phenHH, phenHGH and H’phenH’ is reported, along with the ability of ligands to remove Cu from Aβ, and to prevent the formation of reactive oxygen species catalyzed by Cu and Cu-Aβ, including in presence of zinc, the second metal ions important in the etiology of Alzheimer’s disease. The importance of the reduced state of copper, Cu(I), in the prevention and arrest of ROS is mechanistically described with the help of cyclic voltammetry experiments.