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We synthesised a sequence of structurally related copper(II) complexes of Schiff base ligands, 2-[(2-benzylamino-ethylimino)-methyl]-phenol [L1(H)], 2-[(2-benzylamino-ethylimino)-methyl]-4-methyl-phenol [L2(H)], and 2-[(2-benzylamino-ethylimino)-methyl]-4-bromo-phenol [L3(H)]. The complexes were characterized by ATR, UV-vis, EPR, ESI-MS, single crystal XRD, and elemental analyses. Based on the crystal structure, the ligand was coordinated to the copper(II) centre in a tridentate mode through phenolate(oxygen), imine nitrogen and amine nitrogen in an NNO fashion and the azide moiety served as an auxiliary ligand. Furthermore, we have investigated the antimicrobial activities of copper(II) complexes against clinically relevant fungal strains, including Candida albicans, Candida glabrata, and Candida tropicalis, as well as bacteria such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), representing Gram-negative and Gram-positive pathogenic strains. Comparing the activity of complex 2 (128–512 μg mL−1) to complex 3 (64–128 μg mL−1), the latter demonstrated more potent effectiveness against all of the tested fungal strains. The activity of the complexes against MRSA reveals the inhibitory concentrations of 1024 μg mL−1 for 1, 128 μg mL−1 for 2, and 256 μg mL−1 for 3. It is worth mentioning that, at their minimum inhibitory concentrations (MICs), the complexes are not toxic to Galleria mellonella. Furthermore, the spot and broth microdilution assay results were in good agreement with the actual metabolic viability of bacterial and fungal strains, in which the complexes were active while having no effect on the metabolite resazurin. Additionally, in silico studies have been employed to elucidate both non-bonding interactions and the mode of action across protein sequences of experimentally studied microbes. The performance of complexes closely mirrored the reactivity order determined in in vitro studies. The impeding properties of complexes can be due to the dysfunctioning of virulent genes and signalling proteins and also affect the activities of transferase and transcriptase proteins. Overall, the complexes are promising candidates for antimicrobial drug development. We anticipate utilising these molecules for clinical purposes. [ABSTRACT FROM AUTHOR]

Eight novel mixed-ligand copper(II) complexes of the type [Cu(L)(phen)](ClO4) (1–8) synthesized from S-methyldithiocarbazate Schiff bases [H(L1)–H(L8)] and 1,10-phenanthroline (phen) ligands have been characterized using various physicochemical, spectroscopic and electrochemical methods. The structures of seven out of the eight Cu(II) complexes have been determined by single crystal X-ray diffraction. The coordination geometry around the Cu(II) ion is distorted square pyramidal (τ, 0.24–0.49). The heterocyclic and azomethine nitrogens along with thiolato sulphur of the deprotonated tridentate ligand (NNS) and one of the imine nitrogens of phen form the equatorial CuN3S square plane, while the other imine nitrogen atom of phen occupies the axial position. The geometry of the Cu(II) center in the solid state is preserved in DMF solution, stabilizing to distorted square pyramidal, as suggested by the low-temperature EPR data g‖ > g⊥ > 2.0. Cyclic voltammetry showed that the Cu(II) complexes display quasi-reversible electrochemistry. The efficiency of the complexes in killing the human lung epithelial adenocarcinoma cells (A549) has also been studied along with the cell viability assay against the noncancerous human lung epithelial cells (L132) under in vitro conditions. They were found to exhibit excellent cytotoxicity against A549 cancer cells without affecting the normal L132 cells. The activity of all the complexes was significantly superior to that of cisplatin. The 2′,7′-dichlorodihydrofluorescein diacetate (DCHF-DA) experiment indicated that cancer cells produce more reactive oxygen species (ROS) than normal cells. Further, they cause cell death mainly through apoptotic mode, as revealed by the observation of a higher percentage of apoptotic cells in acridine orange (AO) or ethidium bromide (EB) or 4′,6′-diamidino-2-phenylindole (DAPI) stained cancer cells. Thus, ROS generation in tumor cells is implicated in cytotoxicity, demonstrating the versatile nature of presently accessible mixed-ligand copper(II) complexes for cancer therapy by means of ROS-induced apoptotic cell death. [ABSTRACT FROM AUTHOR]

Recently, mixed-ligand copper(II) complexes have received much attention in searching for alternative metallodrugs to cisplatin. A series of mixed ligand Cu(II) complexes of the type [Cu(L)(diimine)](ClO4) 1–6, where the HL is 2-formylpyridine-N4-phenylthiosemicarbazone and the diimine is 2,2′-bipyridine (1), 4,4′-dimethyl-2,2′-bipyridine (2), 1,10-phenanthroline (3), 5,6-dimethyl-1,10-phenanathroline (4), 3,4,7,8-tetramethyl-1,10-phenanthroline (5) and dipyrido-[3,2-f:2′,3′-h]quinoxaline (6), has been synthesized and their cytotoxicity in HeLa cervical cancer cells examined. In the molecular structures of 2 and 4, as determined by single-crystal X-ray studies, Cu(II) assumes a trigonal bipyramidal distorted square-based pyramidal (TBDSBP) coordination geometry. DFT studies reveal that the axial Cu–N4diimine bond length, interestingly, varies linearly with the experimental CuII/CuI reduction potential as well as the trigonality index τ of the five-coordinate complexes, and that methyl substitution on diimine co-ligands tunes the extent of the Jahn–Teller distortion at the Cu(II). While 4 is involved in strong DNA groove binding with a hydrophobic interaction of methyl substituents, 6 is involved in stronger binding through partial intercalation of dpq with DNA. Complexes 3, 4, 5, and 6 efficiently cleave supercoiled DNA into NC form in ascorbic acid by generating hydroxyl radicals. Interestingly, 4 exhibits higher DNA cleavage in hypoxic than at normoxic conditions. Notably, except for [CuL]+, all the complexes were stable in 0.5% DMSO-RPMI (without phenol red) cell culture medium up to 48 h at 37 °C. Remarkably, all the complexes show time-dependent cytotoxicity at nanomolar concentrations (IC50, 7.0–182 nM) in HeLa cervical cancer cells compared with uncoordinated ligand HL (IC50 > 10 000 nM). Except for 2 and 3, all the complexes exhibit higher cytotoxicity than [CuL]+ at 48 h. 4 shows (57.2 nM) higher cytotoxicity than 1 (181.5 nM) at 24 h incubation; however, notably, 1 demonstrates phenomenal cytotoxicity (7.0 nM) higher than 4 (13.6 nM) at 48 h incubation. The selectivity index (SI) reveals that complexes 1 and 4 are 53.5 and 37.3, respectively, times less toxic to HEK293 normal cells than to cancerous cells. Except for [CuL]+, all the complexes generate ROS to different extents at 24 h, with 1 producing the highest amount, which is consistent with their redox properties. Also, 1 and 4 exhibit, respectively, sub-G1 and G2-M phase cell arrest in the cell cycle. Therefore, complexes 1 and 4 have the potential to emerge as promising anticancer agents. [ABSTRACT FROM AUTHOR]

The fixation of atmospheric CO2 into value‐added products is a promising methodology. A series of novel nickel(II) complexes of the type [Ni(L)(CH3CN)2](BPh4)21–5, where L=N,N‐bis(2‐pyridylmethyl)‐N′, N′‐dimethylpropane‐1,3‐diamine (L1), N,N‐dimethyl‐N′‐(2‐(pyridin‐2‐yl)ethyl)‐N′‐(pyridin‐2‐ylmethyl) propane‐1,3‐diamine (L2), N,N‐bis((4‐methoxy‐3,5‐dimethylpyridin‐2‐ylmethyl)‐N′,N′‐dimethylpropane‐1,3‐diamine (L3), N‐(2‐(dimethylamino) benzyl)‐N′,N′‐dimethyl‐N‐(pyridin‐2‐ylmethyl) propane‐1,3‐diamine (L4) and N,N‐bis(2‐(dimethylamino)benzyl)‐N′, N′‐dimethylpropane‐1,3‐diamine (L5) have been synthesized and characterized as the catalysts for the conversion of atmospheric CO2 into organic cyclic carbonates. The single‐crystal X‐ray structure of 2 was determined and exhibited distorted octahedral coordination geometry with cis‐α configuration. The complexes have been used as a catalyst for converting CO2 and epoxides into five‐membered cyclic carbonates under 1 atmospheric (atm) pressure at room temperature in the presence of Bu4NBr. The catalyst containing electron‐releasing −Me and ‐OMe groups afforded the maximum yield of cyclic carbonates, 34% (TON, 680) under 1 atm air. It was drastically enhanced to 89% (TON, 1780) under pure CO2 gas at 1 atm. It is the highest catalytic efficiency known for CO2 fixation using nickel‐based catalysts at room temperature and 1 atm pressure. The electronic and steric factors of the ligands strongly influence the catalytic efficiency. Furthermore, all the catalysts can convert a wide range of epoxides (ten examples) into corresponding cyclic carbonate with excellent selectivity (>99%) under this mild condition. [ABSTRACT FROM AUTHOR]

The title compound, [Cu(C11H15N2O)(C12H8N2)]ClO4 or [Cu(L)(phen)]-(ClO4) {where L refers to the deprotonated form of 2-[(2-dimethylaminoethylimino) methyl]phenol} and phen is 1,10-phenanthroline) is a mononuclear mixed ligand copper(II) complex. The CuII atom is coordinated by two N and one O atoms of the tridentate Schiff base ligand (HL) and two N atoms of the 1,10-phenanthroline ligand, resulting in a five-coordinate complex. The asymmetric unit of the title complex contains two crystallographically independent complex cations (a and b) with a slightly different geometry around the CuII ion. The value of the trigonality index τ, indicates that in both cations a and b, the CuII atoms display a square-pyramidal distorted trigonal-bipyramidal (SPDTBP) geometry, although the distortion is greater for cation a. [ABSTRACT FROM AUTHOR]

Three new iron(III) complexes of sterically hindered tripodal monophenolate ligands are obtained and studied. The relatively high Fe-O-C bond angle of 136.1 degree is observed in one of the complexes, which is due to the steric demand imposed by the coordinated -NMe2 group nearby.

Whether turns play an active or passive role in protein folding remains a controversial issue at this juncture. Here we use a photolabile cage strategy in combination with laser-flash photolysis and photoacoustic calorimetry to study the effects of different turns on the kinetics of [beta]-hairpin refolding on a nanosecond time scale. This strategy opens up a temporal window to allow the observation of early kinetic events in the protein refolding process at ambient temperature and pH without interference from any denaturants. Our results provide direct evidence demonstrating that even a one-residue difference in the turn region can change the refolding kinetics of a peptide. This observation suggests an active role for turn formation in directing protein folding.