C2 Complex Research Articles

Novel half-sandwich ruthenium(II) nicotinic hydrazone complexes: An efficient class of catalyst for the N-alkylation of amines with benzyl alcohol via transfer hydrogen mechanism and effective antibacterial agents

A new series of half sandwich ruthenium(II) complexes supported by nicotinic acid hydrazone derivatives of general formula [Ru(ɳ6-p-cymene)(Cl)(L)], where L represents N’-benzylidenenicotinohydrazide (HL1), N’-(naphthalen-1-ylmethylene)nicotinohydrazide (HL2) or N’-(pyren-1-ylmethylene)nicotinohydrazide (HL3) were synthesized and fully characterized. The solid-state molecular structures of ligands and complexes were elucidated with single-crystal X-ray diffraction. The ligands HL1 and HL2 possess monoclinic crystal system with P21/c and C2/c space groups respectively, whereas all the three Ru(II) complexes C1–3 are typical three-legged piano-stool geometries with orthorhombic(Aba2) (C1) and triclinic(P-1) (C2–3) systems respectively. The catalytic activities of these ruthenium complexes in the synthesis of N-alkylated amines were explored. Under optimal reaction condition, the complex C3 was found to be the most efficient catalyst for the N-alkylation of primary to secondary amines using benzyl alcohol. A wide range of substrates have been studied that includes anilines bearing electron withdrawing/electron donating group, fused aromatic, heteroaromatic, alicyclic and aliphatic amines with good to excellent yield. In addition, the antibacterial activity of the complexes were tested against different human pathogenic bacteria, among them C2 complex with naphthyl moiety was found to be the most active one against both Gram-positive (S. aureus and E. faecalis) and Gram-negative (E. coli and K. pneumoniae) bacteria. These two different studies demonstrate the catalytic and biological importance of our newly prepared Ruthenium complex.

Synthesis and Characterization of Iridium(III) Complexes with Substituted Phenylimidazo(4,5-f)1,10-phenanthroline Ancillary Ligands and Their Application in LEC Devices.

In this work, we report on the synthesis and characterization of six new iridium(III) complexes of the type [Ir(C^N)2(N^N)]+ using 2-phenylpyridine (C1-3) and its fluorinated derivative (C4-6) as cyclometalating ligands (C^N) and R-phenylimidazo(4,5-f)1,10-phenanthroline (R = H, CH3, F) as the ancillary ligand (N^N). These luminescent complexes have been fully characterized through optical and electrochemical studies. In solution, the C4-6 series exhibits quantum yields (Ф) twice as high as the C1-3 series, exceeding 60% in dichloromethane and where 3MLCT/3LLCT and 3LC emissions participate in the phenomenon. These complexes were employed in the active layer of light-emitting electrochemical cells (LECs). Device performance of maximum luminance values of up to 21.7 Lx at 14.7 V were observed for the C2 complex and long lifetimes for the C1-3 series. These values are counterintuitive to the quantum yields observed in solution. Thus, we established that the rigidity of the system and the structure of the solid matrix dramatically affect the electronic properties of the complex. This research contributes to understanding the effects of the modifications in the ancillary and cyclometalating ligands, the photophysics of the complexes, and their performance in LEC devices.

Synthesis of pH-dependent Ni(II) coordination complexes with Schiff base and their structural characterization

This article describes the study of two Nickel (Ni(II)) complexes based on Schiff base at pH 7.0 and pH 9.0 respectively and characterized using various characterization techniques. The reaction of C7H9N3S2 with NiCl2·6H2O at pH 7.0 resulted in the C1 complex. However, when the same reaction was performed at pH 9.0, C2 complex was obtained. The magnetic behavior (µ) of both complexes was found to be 2.92 (C1) and 2.96B.M. (C2) respectively, which showed that both complexes were paramagnetic and in octahedral shape. In a similar fashion, the electrical conductance of (181.0 Ohm-1cm2 mole-1 for (C1) and (179 Ohm−1 cm2 mole-1 for (C1) suggested that the compound was found in the 1:2 (Metal: Ligand) electrolytically nature in their coordination mode. In the electronic spectrum study, it is clearly shown that both the Ni(II) complexes (9500–10415, 14200–14940, and 23500–24000 cm−1) were octahedral. The broad band at 3350–3600 cm−1 in the IR data of C1 indicates the νOH mode of vibration of the bounded water molecules. Whereas, the 610 cm−1 band is unchanged in the C1 but found red-shifted (600 cm−1) in C2 complex. This indicates that the sulfur of the thiophene unit is not involved in the bonding coordination to metal in C1 but has coordinated with the metal C2 complex.

STRANGULATION-INDUCED ATLANTOAXIAL ROTATORY SUBLUXATION TREATED WITH CLOSED REDUCTION

BackgroundCervical subluxation is a broad class of injuries in which there are degrees of misalignment of vertebral bodies in relationship to adjacent vertebra. Atlantoaxial rotatory subluxation (AARS) is a subtype of cervical subluxation resulting from exaggerated rotation of the C1–C2 complex. Inflammatory, infectious, post-surgical, and traumatic etiologies are recognized and well-described. AARS is predominantly seen in children and occurs rarely in adults. Case ReportWe submit the case of an otherwise healthy adult male patient presenting to the emergency department with strangulation-induced C1–C2 subluxation with a rotational component that was treated at the bedside by neurosurgery with closed reduction. Why Should an Emergency Physician Be Aware of This? Clinicians must consider a broad range of serious pathologies in a patient presenting with torticollis, especially in the setting of strangulation. Although extremely rare in adults, AARS must be considered in the differential diagnosis, as early identification increases the likelihood of successful nonoperative treatment.

Characteristics of staphylococcal cassette chromosome mec and lugdunin operon genes in the complete genome of Staphylococcus lugdunensis.

Characteristics of staphylococcal cassette chromosome mec and lugdunin operon genes in the complete genome of Staphylococcus lugdunensis.

Crystal structure, in vitro cytotoxicity, DNA binding and DFT calculations of new copper (II) complexes with coumarin-amide ligand

This work describes the synthesis, anticancer activity and electron structure study of two Cu (II) complexes with coumarin-3-formyl-(3-(aminomethyl) pyridine) ligand (L) - C1 (Cu2L2(OAc)4) and C2 (CuL2(NO3)2). The structure of C1 and C2 was confirmed by elemental analysis, FTIR, and single-crystal X-ray analysis. Complex C1 crystallizes as binuclear where two Cu (II) ions are bridged by four acetate ligands while C2 is a mononuclear complex with twisted octahedral geometry. Density functional theory (DFT) calculations revealed that electronic transitions originate from metal-ligand charge transfer and d-d transitions of metal ions. According to the results of UV–Vis and fluorescence titrations, C1 and C2 intercalate with DNA with the binding constants of 6.9 × 105 M−1 and 5.9 × 105 M−1, respectively. The in vitro cytotoxicity assays on four cancer cell lines (HeLa, HepG2, MCF-7 and A549) and a normal HUVEC cell line indicated higher anti-MCF-7 activity of C2 compared with cisplatin (IC50 = 2.86 ± 0.08 μM vs. 9.07 ± 0.10 μM). Moreover, C2 had superior selectivity since IC50 toward HUVEC cells was over 150 μM compared with 0.58 ± 0.05 μM for cisplatin. We concluded that the anti-MCF activity of mononuclear C2 complex is better than that of binuclear C1 and cisplatin. Therefore, C2 has been selected as a hit compound to develop novel non‑platinum anticancer agents through modification of coumarin-amide structure and variation of copper (II) salts.

Vanadium(IV) and vanadium(V) complexes: Syntheses, structural characterization, DFT studies and impact of oral uptake on enhancing insulin activity of diabetic albino rats

Two vanadium complexes in two oxidation states (IV) and (V) have were prepared with 3,4-diaminobenzoic acid and acetylacetone ligands. The chemical formula of the complexes is [VO(DABA)(acac)].3H2O (C1) and [VO2(DABA)(acac)].1/2H2O (C2). The complexes are characterized by using different tools such as; molar conductivity, magnetic susceptibility, spectroscopic techniques (FTIR, UV-Vis., mass, and 1H-NMR), and finally by the DFT calculations. The collected data showed that the ligands bound through two amines (NH2) groups for (DABA) ligand and two carbonyls (C=O) groups for (acac) ligand. The spectroscopic data and the DFT calculations confirmed the mononuclear structure of both complexes. Distorted square pyramidal geometry for the C1 complex and distorted octahedral geometry for the C2 complex have been proposed. The calculations confirmed that the C2 complex is more stable than the C1 complex and the electronic energies are (-1098.98 and -1023.04 a.u.); respectively. The HOMO and the LUMO orbitals of the C2 complex (H = -0.385 and L = -0.228 a.u.) are more negative than that of the C1 complex (H = -0.248 and L = -0.206 a.u.). The bond angles in the two complexes have deviated from that of perfect octahedral and square planar (90° and 180°). The bond lengths between the vanadium atoms and the surrounded nitrogen and oxygen atoms are in the constituted range. The double bond between the vanadium atoms and the oxygen atoms (V=O) is 1.587 in the C1 complex and (1.60 and 1.62) in the C2 complex. The mimic insulin study showed that the C1 and the C2 complexes possess a good insulin-enhancing activity. The study of liver and kidney function parameters demonstrated the superiority of the C2 complex, so it promising result that as an insulin-enhancing factor with the low side effect. However, the C2 complex showed non-toxicity toward liver and kidney biochemical parameters, and that may be due to the oxidation state and the structure of the vanadium metal ion.

Synthesis, anti-tumour activity, and mechanism of benzoyl hydrazine Schiff base-copper complexes

Four new complexes of Cu(II) coordinated to a benzoyl hydrazine Schiff base–[Cu(L1)Cl] (C1), [Cu(L1)Py] (C2), [Cu(L2)NO3] (C3), [Cu(L3)NO3] (C4)– were synthesized and characterized. X-ray crystallography results indicated that all complexes had four-coordinated copper centers. The molecular structures of the complexes were altered by linking the phenyl or pyridyl group with the ligand branch or by attaching a second ligand (Py, pyridine) to the copper center. The IC50 values of the four complexes acting on the selected tumour cells were 2.69–16.32 µM. The C1 and C2 complexes could up-regulate the expression of p21 in order to down-regulate the expression of cyclin D1, cyclin E, and CDK2, which caused the cell cycle to be arrested in the G1 phase. Further studies revealed that the C2 complex was able to stabilize G-quadruplex (G4) DNA structure, including that of the proto-oncogene c-kit and the Pu27 sequence situating the promoter region of c-myc, which led to the significant inhibition the expression of c-myc and c-kit. This affected the expression of downstream proteins, such as hTERT and Bcl-2, ultimately inducing apoptosis.

Modeling of Ca12O12, Mg12O12, and Al12N12 nanostructured materials as sensors for phosgene (Cl2CO)

The utilization of 3D nano-materials as sensors and detectors for several systems is continuously being exploited, moreover, the detection limit by already existing devices is still below the hallmark of 100% efficiency. Hence the efficacy of Al12N12, Ca12O12, and Mg12O12-nanostructured materials is exploited in this study for the efficient detection of phosgene. Density functional theory (DFT) approach has been utilized to arrive at the various conclusions and to ascertain the adsorption and sensing attributes of the studied nano-materials. The PBE0, ωB97XD, and M06–2X functionals at the 6–311 + +G(d,p) basis set were utilized for the computations of various molecular properties. In all cases, the Ca12O12 nanostructured material emerged as the most suitable surface for the efficient detection of phosgene, this was confirmed by its molecular electronic properties (energy gap), adsorption energy and other topological investigation. This conclusive scientific report was due to stronger adsorptions observed in C2 complex with adsorption energies − 4.7937 and − 4.5378 kcal/mol in PBE0 and ωB97X-D respectively. Also, relatively least energy gap, chemical hardness and electron potential values of 2.0104, 1.0052 and 6.4978 eV in C2 complex, indicating lowest stability and greatest reactivity and conductivity. This result indicates that the adsorption energy values were lesser using ωB97X-D than using PBE0 functional. Therefore, Ca12O12 surface is a better sensor than Al12N12 and Mg12O12 surfaces for phosgene gas adsorption.

New Cu+2 Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents.

Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu(L1)2(H2O)3] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide) and [Cu(L2)2(py)2(H2O)] (C2) (HL2= N-(5-ethyl-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes’ capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

New molybdenum(VI) and vanadium(IV) complexes with 3-aminopyridine and dithiooxamide ligands spectroscopic characterization, DFT calculations, and in vitro cytotoxic activity

Two molybdenum(VI) complexes C1, [MoO2(acac)(APY)] and C2, [MoO2(DTO)(APY)]·H2O, and two vanadium (IV) complexes C3, [VO(H2O)3(APY)]SO4·3/2H2O and C4, [VO(DTO)(H2O)(APY)]SO4, (where APY = 3-aminopyridine, acac = acetylacetone, and DTO = dithiooximide). The complexes were characterized by different spectral techniques such as FTIR, UV–Vis., 1H NMR, mass spectroscopy, and theoretical calculations. The FTIR spectra showed that the (APY) ligand was coordinated by the nitrogen atom of the amine group. The DTO ligand coordinated in different ways depending on the central metal by the two nitrogen atoms with vanadium V(IV), and by the two sulfur atoms with the molybdenum(VI). The mass spectra confirmed the mononuclear structure for all the prepared complexes. The Mo(VI) complexes were diamagnetic, whereas the V(IV) complexes were paramagnetic. The calculations revealed that the prepared complexes were more stable than the free ligands and their HOMOs were (−0.373 and −0.347 a.u.) for molybdenum(VI) complexes and (−0.502 and −0.496) for vanadyl complexes; respectively whereas the LUMOs values were (−0.282 and −0.289 a.u.) for molybdenum(VI) complexes and (−0.418 and −0.429 a.u.) for vanadium(IV) complexes. The complexes were more polarized and softer than the free ligands. The results confirmed that the transition of the electrons is easier in the complexes than the ligands which suggest using the prepared complexes in the photocell in future studies. Based on the obtained experimental and calculated data, distorted pyramidal structures for the V(IV) and Mo(VI) complexes were proposed. The prepared complexes were examined as anti-cancer complexes against different types of cell lines, the cytotoxic activity of the complexes data showed that the C2 complex is the best candidate to be used as an anti-cancer drug.

Copper (II) complexes derived from pyridoxal: Structural correlations, cytotoxic activities, and molecular docking

This article presents the synthesis, characterization, evaluation of the mimetic potential of the catalytic activity of the superoxide dismutase enzyme, cytotoxic effects, evaluation of interactions with CT-DNA, and theoretical calculations of copper (II) mononuclear complexes. The C1, C2, and C3 complexes were obtained from the aldolic condensation between aromatic amines (furfurylamine, 2-thiophenethylamine, and 2-thiophenethylamine) and aromatic aldehydes (salicylic aldehyde, ortho-vanillin, and pyridoxal hydrochloride). The compounds were structurally characterized by X-ray diffraction, cyclic voltammetry, FTIR, and ultraviolet/visible spectroscopies. Although the complexes presented coordination modes with identical organic molecules, there were different coordination geometries. In addition, the varied chalcogen substituents revealed an electrochemical potential quite different from the complexes. The synthesized complexes were subjected to NBT photoreduction (nitrotetrazolium blue chloride) to quantify the antioxidant activity, and values of the McCord-Fridovich assay showed that the synthesized complexes have significant superoxide dismutation activity. Moreover, CuII complexes were tested in fluorimetric assays, colorimetric assays to assess cellular metabolic activity, and the dichlorofluorescein diacetate test. Our findings showed that the C2 complex presented the best antioxidant activity with the safest reactive oxygen species generation levels and the least damage to DNA using the evaluated methods. Finally, we evaluated how the synthesized complexes interacted with calf thymus deoxyribonucleic acid by spectroscopic techniques (absorption and emission) and theoretical calculations.

Endonasal Odontoidectomy in Basilar Invagination.

Objective The endoscopic endonasal odontoidectomy (EEO) is emerging as a feasible surgical alternative to conventional microscopic transoral approach. In this article, we show EEO in the basilar invagination (BI) and describe in detail the technical aspects, advantages, and disadvantages of this approach ( Fig. 1 ). Methods We describe EEO using audiovisual material from the neurosurgical department of Hospital Universitari i Politècnic La Fe Valencia database. Results We present the case of a 61-year-old male patient with BI. Initially, we performed suboccipital decompression and occipitocervical fusion. Subsequently, after a no significant neurological improvement and persistent anterior compression, EEO was performed. The postoperative evolution was uneventful and the preoperative neurological deficits were recovered rapidly after surgery Discussion EEO technique enables complete odontoid resection, preventing invasion of aggressive oral bacterial flora, and it is not limited by the mouth opening. As well, it avoids manipulation of the soft palate, therefore evades the risk of velopalatal insufficiency, facilitates immediate oral tolerance, and early extubation. The rostral position of C1–C2 complex in BI could suppose a great advantage in favor the endonasal approaches. Mucoperichondrial vascularized flaps could be obtained to avoid a postoperative cerebrospinal fluid (CSF) leak and facilitate the reepithelization process of the surgical bed. Conclusion EEO may provide a significant anatomic and technical advantage over the trans-oral approach. The link to the video can be found at: https://youtu.be/Td6MDcjCNKk .

Isolable dicarbon stabilized by a single phosphine ligand.

In contrast to naturally occurring F2, O2 and N2, diatomic C2 is an intriguing species that has only been observed indirectly in the gas phase, and because of its high reactivity has eluded isolation in the condensed phase. It has previously been stabilized in L→C2←L compounds but the bonding situation of the central C2 in this motif differs remarkably from that of free C2. Here we have prepared and structurally characterized diatomic C2 as a monoligated complex L→C2 using a bulky phosphine ligand bearing two imidazolidin-2-iminato groups (L is (NHCR=N)2(CH3)P, where NHCR is an N-heterocyclic carbene). The compound is stable in solution at ambient temperature and has also been isolated in the solid state. Reactivity studies, in combination with quantum chemical analysis, suggest that the two carbon atoms of the L→C2 complex both have carbene character. The complex underwent intermolecular C-H bond activation upon thermolysis and exhibited hydroalkoxylation-like reactivity with methanol.

Investigation of inclusion complex of metformin into selective cyclic peptides as novel drug delivery system: Structure, electronic properties, AIM, and NBO study via DFT

AbstractIn this study, the density functional theory computational method is used to investigate the encapsulation process of metformin into three types of the cyclic peptides composed of eight serine (CP1), eight glycine (CP2), and four serine‐glycine (CP3) cyclic peptides as a new model in the process of drug delivery in the gas phase. The obtained results using the B3LYP/6‐31++G (d,p) method indicate that the complexes formed are energetically favored. Furthermore, results reveal that the drug encapsulation process is typically chemisorption. The natural bonding orbital analysis shows that the intermolecular interaction of the C2 complex (metformin/CP2) is stronger than the C1 (Metformin/CP1) and C3 (Metformin/CP3) complexes due to greater total charge transfer energy, and the C1 complex is found to be the most favored complex. The theory of atoms in molecule (AIM) method is used to analyze the nature of interactions in different molecular systems. The results show the investigated cyclic peptides as effective carriers of metformin in the nanomedicine field.

In vitro assessments of cytotoxic and cytostatic effect of two [Cu(dien)(N-N)]Br2 complexes on L6, HCT, PC3 and HepG2 cancer cells

Two new Cu(II) complexes of type [Cu(dien)(N-N)] Br 2 (dien is diethlylenetriamine, C1 complex with N-N = diethlylenetriamine and C2 complex with N-N = propyl-1,3-diamine) were made valuable and in vitro screened for both cytostatic and cytotoxic activities against four cell lines: colon cancer (HCT), liver cancer (HepG2), prostate cancer (PC3) and as control cell (L6) human muscle cell was used via MTT test. The results reflected these complexes as a promising activity antiprolifrative agent against the used cell lines indicating that C1 and C2 complexes have a high anticancer activity at non-toxic concentrations.

Dissecting the cytochrome c2-reaction centre interaction in bacterial photosynthesis using single molecule force spectroscopy.

The reversible docking of small, diffusible redox proteins onto a membrane protein complex is a common feature of bacterial, mitochondrial and photosynthetic electron transfer (ET) chains. Spectroscopic studies of ensembles of such redox partners have been used to determine ET rates and dissociation constants. Here, we report a single-molecule analysis of the forces that stabilise transient ET complexes. We examined the interaction of two components of bacterial photosynthesis, cytochrome c2 and the reaction centre (RC) complex, using dynamic force spectroscopy and PeakForce quantitative nanomechanical imaging. RC–LH1–PufX complexes, attached to silicon nitride AFM probes and maintained in a photo-oxidised state, were lowered onto a silicon oxide substrate bearing dispersed, immobilised and reduced cytochrome c2 molecules. Microscale patterns of cytochrome c2 and the cyan fluorescent protein were used to validate the specificity of recognition between tip-attached RCs and surface-tethered cytochrome c2. Following the transient association of photo-oxidised RC and reduced cytochrome c2 molecules, retraction of the RC-functionalised probe met with resistance, and forces between 112 and 887 pN were required to disrupt the post-ET RC–c2 complex, depending on the retraction velocities used. If tip-attached RCs were reduced instead, the probability of interaction with reduced cytochrome c2 molecules decreased 5-fold. Thus, the redox states of the cytochrome c2 haem cofactor and RC ‘special pair’ bacteriochlorophyll dimer are important for establishing a productive ET complex. The millisecond persistence of the post-ET cytochrome c2[oxidised]–RC[reduced] ‘product’ state is compatible with rates of cyclic photosynthetic ET, at physiologically relevant light intensities.

Probing the Effect of Cardiolipin on the Redox-Partner Recognition between Cytochrome C2 and Cytochrome Bc1 Complex

Cytochrome c (cyt. c) and cytochrome bc1 (bc1) complex are redox proteins that participate in the electron transport chain of the mitochondria, with cyt. c shuttling electrons from bc1 complex to complex IV. Cyt. c and bc1 complex reside in the inner membrane of the mitochondria, which is rich in the negatively-charged cardiolipin (CL). CL concentration in mitochondria varies upon different physiological conditions, and in some cases, a depletion of CL leads to a reduced bc1 complex activity. In this study, the redox-partner recognition between cyt. c and bc1 complex is examined using molecular dynamic (MD) and Brownian dynamics (BD) simulations with variations in CL concentration and salinity. First, MD simulations were performed to equilibrate cyt c2 and bc1 complex with membranes of different CL concentrations to obtain atomistic representations of their in situ configurations. Then, for each CL concentration, the electrostatic potential profile as well as hydrophobic interactions under different salinities were determined; to serve as input parameters for BD simulations. Then, for each redox state of cyt. c2 and that of bc1 complex, as well as for each of the above-mentioned CL concentration, a set of 10 independent 200 microsecond BD simulations were performed to sample the binding likelihood between the two proteins. Our result shows that a match between the redox state of cyt. c2 and that of bc1 complex promotes the binding of the two proteins in all different conditions. However, the ability of cyt. c2 to distinguish bc1 complex from the membrane surface is susceptible to the corresponding electrostatic potential profile, which can be significantly modified by variations in CL concentration and salinity.

Ruthenium complexes of pyridine oxime and azoimine ligands: Syntheses, crystallography, electrochemical and catalytic properties

Five mononuclear ruthenium complexes of the type trans-[RuCl2(Azo)(Py-C(R)N = OH)] (C1–C5) {Azo = C6H5N = NC(COCH3) = NC6H4X, R = CH3, X = H (C1), Br (C2), CH3 (C3), F (C4); R = H, X = CH3 (C5)} have been synthesised and characterized by spectroscopic (IR, UV-Vis, and NMR) and electrochemical (cyclic voltammetry) techniques. In addition, C2 complex has been further characterized by single crystal X-ray diffraction. The complexes (C1-C3) were also tested with respect to their catalytic activity in the liquid-phase hydrogenation of acetophenone. The electronic absorption spectrum of C2 in acetonitrile has been modelled by time-dependent density functional theory.

The phosphoinositide 3-kinase pathway and glycogen synthase kinase-3 positively regulate the activity of metal-responsive transcription factor-1 in response to zinc ions.

Metal-responsive transcription factor-1 (MTF-1) is a metal-regulatory transcription factor essential for induction of the genes encoding metallothioneins (MTs) in response to transition metal ions. Activation of MTF-1 is dependent on the interaction of zinc with the zinc fingers of the protein. In addition, phosphorylation is essential for MTF-1 transactivation. We previously showed that inhibition of phosphoinositide 3-kinase (PI3K) abrogated Mt expression and metal-induced MTF-1 activation in human hepatocellular carcinoma (HCC) HepG2 and mouse L cells, thus showing that the PI3K signaling pathway positively regulates MTF-1 activity and Mt gene expression. However, it has also been reported that inhibition of PI3K has no significant effects on Mt expression in immortalized epithelial cells and increases Mt expression in HCC cells. To further characterize the role of the PI3K pathway on the activity of MTF-1, transfection experiments were performed in HEK293 and HepG2 cells in presence of glycogen synthase kinase-3 (GSK-3), mTOR-C1, and mTOR-C2 inhibitors, as well as of siRNAs targeting Phosphatase and TENsin homolog (PTEN). We showed that inhibition of the mTOR-C2 complex inhibits the activity of MTF-1 in HepG2 and HEK293 cells, while inhibition of the mTOR-C1 complex or of PTEN stimulates MTF-1 activity in HEK293 cells. These results confirm that the PI3K pathway positively regulates MTF-1 activity. Finally, we showed that GSK-3 is required for MTF-1 activation in response to zinc ions.