Aminomethyl Pyridine Research Articles

Two different coordination modes of the Schiff base derived from ortho-vanillin and 2-(2-aminomethyl)pyridine in a mononuclear uranyl complex

This work describes the reaction of the potentially tetradentate Schiff-base ligand N-(2-pyridylmethy)-3-methoxysalicylaldimine (HL) with UO2(O2CMe)2·2H2O and UO2(NO3)2· 6H2O in MeOH in the absence or presence of an external base, respectively. The product from these reactions is the mononuclear complex [UO2(L)2] (1). Its structure has been determined by single-crystal, X-ray crystallography. The anionic ligand adopts two different coordination modes (1.1011, 1.1010; Harris notation) in the complex. The new compound was fully characterized by solid-state (IR, Raman and Photoluminescence spectroscopies) and solution (UV-Vis and 1H NMR spectra, conductivity measurements) techniques.

Enzymatic Synthesis of Chemical Nuclease Triplex-Forming Oligonucleotides with Gene-Silencing Applications.

Triplex-forming oligonucleotides (TFOs) are short, single-stranded oligomers that hybridise to a specific sequence of duplex DNA. TFOs can block transcription and thereby inhibit protein production, making them highly appealing in the field of antigene therapeutics. In this work, a primer extension protocol was developed to enzymatically prepare chemical nuclease TFO hybrid constructs, with gene-silencing applications. Click chemistry was employed to generate novel artificial metallo-nuclease (AMN)-dNTPs, which were selectively incorporated into the TFO strand by a DNA polymerase. This purely enzymatic protocol was then extended to facilitate the construction of 5-methylcytosine (5mC) modified TFOs that displayed increased thermal stability. The utility of the enzymatically synthesised di-(2-picolyl)amine (DPA)-TFOs was assessed and compared to a specifically prepared solid-phase synthesis counterpart through gel electrophoresis, quantitative PCR, and Sanger sequencing, which revealed similar recognition and damage properties to target genes. The specificity was then enhanced through coordinated designer intercalators—DPQ and DPPZ—and high-precision DNA cleavage was achieved. To our knowledge, this is the first example of the enzymatic production of an AMN-TFO hybrid and is the largest base modification incorporated using this method. These results indicate how chemical nuclease-TFOs may overcome limitations associated with non-molecularly targeted metallodrugs and open new avenues for artificial gene-editing technology.

Aminomethylpyridine isomers functionalized cellulose microspheres for TcO4-/ReO4- uptake: Structure-properties relationship and their application in different aquatic systems

Technetium-99 (99Tc) is a long-lived radioactive nuclide that poses great threat to environment, hence selective removal of 99Tc from aquatic system is always an issue. Aminomethylpyridine (AMP) equipped with pyridine and amino, is a promising receptor for TcO4- and its surrogate ReO4-, thus it is of interest to explore and understand the structure-properties relationship of ReO4- adsorption related to n-AMP structure that differ in amino methyl position. In this work, three n-AMP functionalized cellulose microspheres (n-AMPR, n = 2, 3, 4) were synthesized and employed for TcO4-/ReO4- uptake. The effect of aminomethyl position on adsorption properties of n-AMPR for ReO4- were investigated and compared. Adsorption kinetics and adsorption isotherm showed that adsorption speed and adsorption capacity were in order of 3-AMPR > 2-AMPR > 4-AMPR. DFT calculation verified that the adsorption of ReO4- by n-AMPR was attributed to electrostatic interaction and hydrogen bonding interaction, the order of adsorption abilities of n-AMPR was due to that steric effect and hydrogen bond collaborated in stabilizing n-AMPR-ReO4- complexes. The column experiments demonstrated that 3-AMPR can be selectively remove ReO4- from simulated groundwater. More importantly, 99Tc column experiments showed that 3-AMPR had a better ability for actual radioactive TcO4-.

Di-(2-picolyl)amine functionalized tetraphenylethylene as multifunctional chemosensor

In this study, we successfully developed a new multifunctional chemosensor 4′,4‴-(2,2-diphenylethene-1,1-diyl)bis(N,N-bis (pyridin-2-ylmethyl)-[1,1′-biphenyl]-4-amine (T-D), based on the cooperation of tetraphenylethylene and di-(2-picolyl)amine (DPA), for sensitive, selective, and quick detection of Cu2+, PO43− and pesticide glyphosate in aqueous solution. In our research, we made full use of the Cu2+-indicator displacement strategy to achieve the construction of an “on-off-on” fluorescent switch platform. Due to the presence of the DPA moiety in T-D, Cu2+ could be captured quickly to form the complex T-D-Cu and caused fluorescence quenching. With the addition of PO43− and glyphosate, the system could rapidly restore the fluorescence by squeezing Cu2+ from T-D-Cu and blocking the photo induced electron transfer (PET) process to display the aggregation-induced emission. To demonstrate the possibility of practical applications, we detected PO43− and glyphosate in spiked real samples. The detection limit for PO43− and glyphosate reached 19 nM and 25 nM, respectively. Furthermore, test strips using T-D-Cu solution simplified the detection process of glyphosate. More importantly, the sensor could be used in visual semi-quantitative determination of PO43− concentrations in both living cells and living zebra fish. Therefore, the chemosensor presented here will not only be a powerful tool for the detection of phosphate anions in aqueous solution and biological systems, but also provides a new template for the design of other multifunctional chemosensors.

A sensitive zinc probe operating via enhancement of excited-state intramolecular charge transfer.

Novel highly sensitive fluorescent probes for zinc cations based on the diketopyrrolopyrrole scaffold were designed and synthesized. Large bathochromic shifts (≈80 nm) of fluorescence are observed when the Zn2+-recognition unit (di-(2-picolyl)amine) is bridged with the fluorophore possessing an additional pyridine unit able to participate in the coordination process. This effect originates from the dipolar architecture and the increasing electron-withdrawing properties of the diketopyrrolopyrrole core upon addition of the cation. The new, greenish-yellow emitting probes, which operate via modulation of intramolecular charge transfer, are very sensitive to the presence of Zn2+. Introduction of a morpholine unit in the diketopyrrolopyrrole structure induces a selective six-fold increase of the emission intensity upon zinc coordination. Importantly, the presence of other divalent biologically relevant metal cations has negligible effects and typically even at a 100-fold higher concentration of Mg2+/Zn2+, the effect is comparable. Computational studies rationalize the strong bathochromic shift upon Zn2+-complexation. Decorating the probes with the triphenylphosphonium cation and morpholine unit enables selective localization in the mitochondria and the lysosome of cardiac H9C2 cells, respectively.

Synthesis, single crystal structures, DFT and in vitro anti oxidant superoxide dismutase studies of copper(II) complexes derived from the di-(2-picolyl)amine and co-ligands: Promising antioxidants

Three new copper(II) complexes, [Cu(DPA)(ClO4)2(H2O)]MAP 1, [Cu(DPA)(ImH)(ClO4)2] 2 and [Cu2(DPA)2(2COO−)(ClO4)2]H2O 3 (where, DPA = di-(2-picolyl)amine, MPA = 2-methoxyacetophenone, ImH = Imidazole and 2COO− = oxalate anion), have been synthesized and characterized using various physico-chemical techniques. DPA is a tridentate ligand with NNN donors atoms and imidazole is a monodentate ligand whereas, oxalate anion is a bridging ligand. Single crystal X-ray analysis reveals that 1–3 are neutral complexes. The X-band Epr spectral study in polycrystalline at RT and in DMSO solution at LNT have been analyzed. To examine the stability of complexes, density functional theory (DFT) calculations were performed. The obtained quantum chemical parameters like electron affinity, ionization potential, electronegativity, electrophilicity and global hardness and softness were discussed within the frame work of electronic structures and principles known as maximum hardness, minimum polarizability and minimum electrophilicity principles. Hirshfeld surface analysis showed that the supramolecular structures of the complexes 1–3 is stabilized mainly by CH⋯π, lp⋯π and various hydrogen bonding intermolecular interactions. Complex 3 shows ferromagnetic interaction, with J = +1.5 cm−1, due to perchlorate bridging anion complex. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) support the electrochemical features of these complexes. The Hirshfeld surface analysis exhibited short-range forces of the hydrogen bonds in all studied complexes. In addition, antioxidant superoxide dismutase activity measurements of these complexes were also performed and discussed. The increased SOD activity of 1 can be assigned due to presence of labile coordinated water molecule. The results of SOD activity reveal that the coordination geometries have significant effect on the SOD catalytic activity.

Lactide polymerization using a sterically encumbered, flexible zinc complex

4-(tert-Butyl)-2-trityl-6-(di-(2-picolyl)amine)phenol, LH, was prepared from paraformaldehyde, 4-(tert-butyl)-2-tritylphenol, and di-(2-picolyl)amine. Reaction with Zn(N(SiMe3)2)2 gave LZnN(SiMe3)2. The complex was shown by X-ray diffraction study, variable temperature NMR, and DFT calculations to coordinate only one pyridine ligand, which allows for fast and facile complex isomerisation. LZnN(SiMe3)2 was active in rac-lactide polymerization, but in contrast to previous complexes of this type, it did not show any evidence for isotactic monomer enchainment via a catalytic-site mediated chain-end control mechanism. Addition of alcohol led to increased activity, but the complex was unstable in the presence of free alcohol.

Development of DNA intercalative, HSA binder pyridine‐based novel Schiff base Cu(II), Ni(II) complexes with effective anticancer property: A combined experimental and theoretical approach

AbstractThe two novel Cu(II) complexes [Cu(L)(CH3COO)] and [Cu(L)(N3)] (1, 2) and one Ni(II) complex [Ni(L)(N)3] (3) have been developed by using the ligand HL, obtained by the condensation of 2 amino methyl pyridine and 5‐bromo salicylaldehyde. All the three complexes are spectroscopically characterized along with molar conductance measurement. With the help of EPR, density functional theory (DFT) studies, the occupants of distorted square planer geometry with azide (2 and 3), acetate (1) as a secondary anionic residue, and the presence of +2 oxidation state on metal center of the complexes have been documented. After structural determination, all the complexes have been exposed to inspect their DNA and human serum albumin (HSA) binding efficacy. Initially, the higher binding constants, obtained from electronic titration among complexes and DNA, the impressive reduction of fluorescence intensities of the HSA and Ethidium Bromide (EtBr)‐DNA adduct, after incremental addition of complexes separately, assure the high binding ability of complexes 2 and 3 in compare with 1. The time‐dependent fluorescence study, isothermal titration calorimetry (ITC), and circular dichroism (CD) spectral titration provide the additional support to get affirmation about the binding potentiality of the aforementioned complexes with DNA/HSA. The molecular docking study authenticates the experimental approach. Furthermore, the anticancer study of all the complexes has been checked by implementing the MTT assay method on two cancer cell lines and one normal cell line. The MTT assay results explore the better anticancer property of complex 2 in comparison with complexes 1 and 3 with low toxicity to the normal cell, and this fact may be correlated with the impressive DNA and HSA binding efficacy of complex 2. Finally, the nuclear staining study by AO/PI dual sensor discloses the nuclear morphological change of cancer cells along with the opening of cell death mechanism, suggesting the apoptotic pathway.

Chalcone-based fluorescent chemosensors as new tools for detecting Cu2+ ions

The design and full characterization of new fluorescent chemosensors for Cu2+ is herein presented. The structure of the sensors is based on a chalcone backbone as the chromophoric unit, with di-(2-picolyl)amine (DPA) as a receptor moiety. Two systems, bearing one or two chalcone-DPA units, were synthesized and fully characterized.UV–Vis titrations with several metal ions were performed and both chemosensors exhibited a strong hypsochromic shift in the absorption spectra upon Cu2+ addition, indicating a higher selectivity for this metal over other divalent cations. Additionally, fluorescent spectra recorded in the same conditions revealed a stronger quenching effect in the presence of Cu2+, even in the presence of other metal cations, with association constants above 106 M−1 and detection limits below the micromolar level for both chemosensors. Paper test-strips with one of the chemosensors were prepared to attest its possible application for detecting copper in aqueous samples.

Fe(III)-Complex-Imprinted Polymers for the Green Oxidative Degradation of the Methyl Orange Dye Pollutant.

One of the biggest problems worldwide is the pollution of natural water bodies by dyes coming from effluents used in the textile industry. In the quest for novel effluent treatment alternatives, the aim of this work was to immobilize Fe(III) complexes in molecularly imprinted polymers (MIPs) to produce efficient Fenton-like heterogeneous catalysts for the green oxidative degradation of the methyl orange (MO) dye pollutant. Different metal complexes bearing commercial and low-cost ligands were assayed and their catalytic activity levels towards the discoloration of MO by H2O2 were assessed. The best candidates were Fe(III)-BMPA (BMPA = di-(2-picolyl)amine) and Fe(III)-NTP (NTP = 3,3′,3″-nitrilotripropionic acid), displaying above 70% MO degradation in 3 h. Fe(III)-BMPA caused the oxidative degradation through two first-order stages, related to the formation of BMPA-Fe-OOH and the generation of reactive oxygen species. Only the first of these stages was detected for Fe(III)-NTP. Both complexes were then employed to imprint catalytic cavities into MIPs. The polymers showed catalytic profiles that were highly dependent on the crosslinking agent employed, with N,N-methylenebisacrylamide (MBAA) being the crosslinker that rendered polymers with optimal oxidative performance (>95% conversion). The obtained ion-imprinted polymers constitute cheap and robust solid matrices, with the potential to be coupled to dye-containing effluent treatment systems with synchronous H2O2 injection.

Modulation of catalytic and biomolecular binding properties of ruthenium(II)-arene complexes with the variation of coligands for selective toxicity against cancerous cells

Four ruthenium(II)-arene complexes, viz. [Ru(p-cym)(2-ampy)Cl]PF61, [Ru(benzene)(2-ampy)Cl]SO3CF32, [Ru(p-cym)(2-ampy)PPh3](PF6)23 and [Ru(benzene)(2-ampy)PPh3](SO3CF3)24 [2-ampy = 2-aminomethyl pyridine] have been synthesized and characterized. Different analytical techniques have been utilized to characterize 1–4 and a DFT study was used to optimize the geometries and calculate the energies of the frontier molecular orbitals. An MTT assay revealed the potency of complexes 1–4 against MCF-7 (breast cancer) and Hela (cervical cancer) cell lines. The presence of the triphenyl phosphine ligand in complexes 3 and 4 makes the complexes more cytotoxic with respect to their chloro-analogues. The complexes are found to be specifically cytotoxic against cancerous cell lines only, as they were inactive against the normal HEK 293 cell line. An absorption and fluorescence titration study of complexes 1–4 showed significant interactions with DNA and proteins. Interestingly, all the complexes show potent catalytic activity for the hydrogen transfer of NADH and converted NADH to NAD+, which helps to induce the accumulation of intracellular reactive oxygen species (ROS) in MCF-7 cells. To analyze the morphological changes in the cells, the Hoechst staining method was applied to capture images of apoptotic cells through confocal microscopy.

Synthesis, crystal structure and thermal properties of poly[bis-[μ2-3-(amino-meth-yl)pyridine]-bis-(thio-cyanato)-cobalt(II)

The reaction of Co(NCS)2 with 3-(amino-meth-yl)pyridine as coligand leads to the formation of crystals of the title compound, [Co(NCS)2(C6H8N2)2] n , that were characterized by single-crystal X-ray analysis. In the crystal structure, the CoII cations are octa-hedrally coordinated by two terminal N-bonded thio-cyanate anions as well as two pyridine and two amino N atoms of four symmetry-equivalent 3-(amino-meth-yl)pyridine coligands with all pairs of equivalent atoms in a trans position. The CoII cations are linked by the 3-(amino-meth-yl)pyridine coligands into layers parallel to the ac plane. These layers are further linked by inter-molecular N-H⋯S hydrogen bonding into a three-dimensional network. The purity of the title compound was determined by X-ray powder diffraction and its thermal behavior was investigated by differential scanning calorimetry and thermogravimetry.

Steric and Electronic Effects on the Structure and Photophysical Properties of Hg(II) Complexes.

Since many factors influence the coordination around a metal center, steric and electronic effects of the ligands mainly determine the connectivity and, thus, the final arrangement. This is emphasized on Hg(II) centers, which have a zero point stabilization energy and, thus, a flexible coordination environment. Therefore, the unrestricted Hg(II) geometry facilitates the predominance of the ligands during the structural inception. Herein, we synthesized and characterized a series of six Hg(II) complexes with general formula (Hg(Pip)2(dPy)) (Pip = piperonylate, dPy = 3-phenylpyridine (3-phpy) (1), 4-phenylpyridine (4-phpy) (2), 2,2′-bipyridine (2,2′-bipy) (3), 1,10-phenanthroline (1,10-phen) (4), 2,2′:6′,2′-terpyridine (terpy) (5), or di(2-picolyl)amine (dpa) (6)). The elucidation of their crystal structures revealed the arrangement of three monomers (3, 5, and 6), one dimer (4), and two coordination polymers (1 and 2) depending on the steric requirements of the dPy and predominance of the ligands. Besides, the study of their photophysical properties in solution supported by TD-DFT calculations enabled us to understand their electronic effects and the influence of the structural arrangement on them.

Preclinical Evaluation of a Novel 99mTc-Labeled CB86 for Rheumatoid Arthritis Imaging.

Early diagnosis and therapy are crucial to control disease progression optimally and achieve a good prognosis in rheumatoid arthritis (RA). Previous study showed that a technetium-99m (99mTc)-labeled TSPO ligand (99mTc-CB256 [2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl)H-imidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide] composed of a translocator protein (TSPO) ligand CB86 [[2-(4-chlorophenyl)-8-amino-imidazo[1,2-a]-pyridin-3-yl]-N,N-di-n-propylacetamide] and di-(2-picolyl)amine, a bifunctional chelate agent, was used to image a TSPO-rich cancer cell in vitro; however, few 99mTc-CB256 in vivo evaluation has been reported so far probably due to the cytotoxicity of CB256 (ca. 75 times more than analogous CB86). Herein, we describe a novel TSPO targeting radiopharmaceutical consisting of CB86 and diethylenetriaminepentaacetic acid (DTPA), a conventional bifunctional chelating ligand in clinical trials used to prepare 99mTc-labeled CB86, and its evaluation as a 99mTc-single-photon emission computed tomography (SPECT) probe. The radiosynthesis and characterization of 99mTc-DPTA-CB86 including hydrophilicity and stability tests were determined. Additionally, the binding affinity and specificity of 99mTc-DTPA-CB86 to TSPO were evaluated using RAW264.7 macrophage cells. Biodistribution and 99mTc-SPECT studies were conducted on rheumatoid arthritis (RA) rat models after the injection of 99mTc-DTPA-CB86 with or without co-injection of unlabeled DTPA-CB86. The radiosynthesis of 99mTc-DTPA-CB86 was completed successfully with the labeling yields and radiochemical purity of 95.86 ± 2.45 and 97.45 ± 0.69%, respectively. The probe displayed good stability in vitro and binding specificity to RAW264.7 macrophage cells. In the biodistribution studies, 99mTc-DTPA-CB86 exhibited rapid inflammatory ankle accumulation. At 180 min after administration, 99mTc-DTPA-CB86 uptakes of the left inflammatory ankle were 2.35 ± 0.10 percentage of the injected radioactivity per gram of tissue (% ID/g), significantly higher than those of the normal tissues. 99mTc-SPECT imaging studies revealed that 99mTc-DTPA-CB86 could clearly identify the left inflammatory ankle with good contrast at 30–180 min after injection. Therefore, 99mTc-DTPA-CB86 may be a promising probe for arthritis 99mTc-SPECT imaging.

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes.

Imidazo[1,5-a]pyridines were efficiently prepared via the cyclization of 2-picolylamines with nitroalkanes electrophilically activated in the presence of phosphorous acid in polyphosphoric acid (PPA) medium.

Fluorescent di-(2-picolyl)amine based drug-like ligands and their Re(CO)3 complexes towards biological applications

Herein we report two new fac-Re(I) tricarbonyl complexes, fac-[Re(CO)3(N(SO2)(1-nap)dpa)]PF6 (C1) and fac-[Re(CO)3(N(SO2)(2-nap)dpa)]PF6 (C2), of two naphthalene derivatized tridentate ligands (N(SO2)(1-nap)dpa (L1) and N(SO2)(2-nap)dpa (L2)) and one reported Re(I) complex, fac-[Re(CO)3(N(SO2Me2Nnap)dpa)]PF6 (C3), of a dansyl appended di-2-picolylamine ligand (N(SO2Me2Nnap)dpa (L3)). The properties of the compounds were elucidated using spectrophotometric measurements (UV–Vis, FTIR and 1H NMR). A single crystal X-ray study was carried out for the three ligands. The 1H NMR spectra of the three complexes obtained in DMSO‑d6 displayed two doublets (exo-CH and endo-CH) for the magnetically inequivalent methylene protons, compared to their uncoordinated ligands where the methylene protons show a singlet peak. The formation of the metal complexes was further supported by FTIR spectra in which the SN stretching band for the metal complexes appears at lower wavenumbers compared to that of the corresponding free ligands. In comparison with the uncoordinated ligands, the Re(I) complexes, C1 and C3, displayed a bathochromic shift while C2 showed a hypsochromic shift in the absorption spectra in methanol. The fluorescent maxima and the fluorescence quantum yield (ΦF) of L1 and L2 were 338 nm (ΦF = 0.056) and 343 nm (ΦF = 0.039), respectively. Interestingly, all the compounds except C2 showed excellent fluorescent emissions. Biologically, the compounds were investigated for their cytotoxicity in vitro on human lymphocytes following the Trypan blue dye exclusion method. It was observed that both Re(I) complexes as well as the ligands show low toxicity towards human lymphocytes at working concentrations below 10 mg/ml (L1, L2: 0.026 M, L3: 0.023 M, C1, C2, C3: 0.012 M). In silico studies revealed that the ligands are potential candidates for anti-inflammatory agents and this was further supported by molecular docking studies, in which they showed a higher affinity for Prostaglandin synthase 2. These drug-like molecules, having an affinity to bovine serum albumin, are thus potential drug leads for anti-inflammatory agents.

The first structurally characterized sulfonamide derivatized Zn(II)-dipicolylamine complexes with eight membered chelate rings. Synthetic and structural studies

Di(2-picolyl)amine has attracted a great deal of attention as the most popular chelating group in synthesizing biological sensors to detect zinc(II) ions. This study reveals the first structurally characterized zinc complexes of the sulfonamide derivatized di(2-picolyl)amine (dpa) moiety with a rare eight membered chelate ring. The novel synthesized zinc(II) complexes; Zn(N(SO2R1dpa)Cl2 (C1), Zn(N(SO2R2dpa)Cl2 (C2), Zn(N(SO2R3dpa)Cl2 (C3), where R1 = 1-naphthalene, R2 = 2-naphthalene, R3 = 5-(dimethylamino)naphthalene were characterized using single crystal X-ray diffraction analysis, 1H NMR, FTIR, UV–Visible and fluorescence spectroscopy. Structural analysis showed that the complexes possess distorted tetrahedron geometry around the zinc centre and that the zinc metal centre is bound to the two pyridyl nitrogens of the dpa group in a bidentate fashion creating a large eight membered chelate ring. The signal attributed to the methylene group (CH2) in the free ligand spectra remains a singlet in the 1H NMR spectra of the zinc complexes but has shifted more downfield. Spectral studies of the complexes revealed that the complexes are fluorescent at concentrations of 0.1 mM with intense fluorescence peaks (C1: 335 nm, C2: 343 nm and C3: 528–551 nm) and, thus, can be further investigated on their potential to be used as imaging agents or biological sensors.

Redox cycling of copper by coumarin-di(2-picolyl)amine hybrid molecule leads to ROS-mediated modulation of redox scavengers, DNA damage and cell death in diethylnitrosamine induced hepatocellular carcinoma.

Targeted therapy is a new strategy for cancer treatment that targets chemical entities specific to cancer cells than normal ones. One of the features associated with malignancy is the elevated copper which plays an integral role in angiogenesis. Work is in progress in our lab to identify new copper chelators to target elevated copper under targeted therapy for the killing of cancer cells. Recently, a coumarin-based copper chelator, di(2-picolyl)amine-3(bromoacetyl)coumarin hybrid molecule (ligand-L) has been synthesized by us, and also studied its copper-dependent macromolecular damage response in copper overloaded lymphocytes. The present study investigates the anticancer activity of ligand-L and its mode of action in rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma. It has been found that liver tissue has a marked increase in copper levels in DEN induced hepatocellular carcinoma. Ex vivo results showed that ligand-L inhibited cell viability, induced reactive oxygen species (ROS) generation, DNA damage, loss of mitochondrial membrane potential and caspase-3 activation in isolated hepatocellular carcinoma cells (HCC). All these effects induced by ligand-L were abrogated by neocuproine and N-acetylcysteine (ROS scavenger). Further, ligand-L treatment of animals bearing hepatocellular carcinoma results in an increment in the cellular redox scavengers, lipid peroxidation and DNA breakage in malignant hepatocytes. In vivo studies using ligand-L also showed that ligand-L possesses anticancer properties as evidenced by improvement in liver marker enzymes and liver surface morphology, and reduced alpha-fetoprotein in the treated group compared to untreated cancer-induced group. Overall, this study suggests that copper-ligand-L interaction leads to ROS generation which caused DNA damage and apoptosis in malignant cells. This study provides enough support to establish ligand-L as a clinically relevant lead molecule for the treatment of different malignancies.

Synthesis and catalytic activity of cationic dinuclear palladium (II) complexes supported by thioether ligands containing two di-(2-picolyl) amine arms

The design, synthesis and characterization of a series of dithioether ligands featuring two di-(2-picolyl)amine arms (2a–2d) and their corresponding cationic dinuclear palladium (II) complexes (3a–d) are reported. Crystal structures of ligand 2b and complexes 3b and 3d were determined by X-ray diffraction studies. The molecular structures of 3b and 3d display each of the two di-(2-picolyl)amine fragments coordinated to one palladium(II) atom in a (κ3-N,N,N) tridentate fashion and with the cationic metal centers displaying square-planar geometries. Weak interactions between the metal centers and the thioether fragments are observed. All bimetallic complexes 3a–d were tested as catalytic precursors in the Suzuki couplings of different o- or p-substituted iodo- or bromoaryls with boronic acids. The overall catalytic results indicate that complex 3b is the best precursor of the series demonstrating even more efficient performance compared to commercial palladium sources such as Pd(OAc)2 and the Nájera Catalysts.

Structural Variety of Isopropyl-bis(2-picolyl)amine Complexes with Zinc(II) and Copper(II)

A variety of structurally different complexes of the isopropyl-bis(2-picolyl)amine (iPr-bpa) ligand were prepared with ZnA2 and CuA2 salts (A = Br–, Br–/PF6–, BF4–/F–, ClO4–). The choice of differe...