Main Ligand Research Articles

Syntheses, characterization of Ni(II)/Zn(II) complexes derived from flexible tricarboxylate ligand and 2,2′-bipyridine and their methyl violet dye photodegradation applications

Three new complexes comprising Ni(II) and Zn(II) metal centers having compositions [Zn2(HL)2(bpy)2(H2O)2] (1), [Ni(H2L)(bpy)(H2O)2(OH)] (2) and [Ni(H2L)2(bpy)2] (3) have been synthesized by adopting mixed ligand strategy using 4′-(3,4- dicarboxylphenyloxy) -4-biphenylcarboxylic acid (H3L) as main ligand and 2,2′-bipyridine (bpy) as co-ligand. These complexes have been characterized by microanalyses, FTIR and single crystal X-ray diffraction technique. The single crystal X-ray analyses reveal that all the three complexes have 2D supramolecular network constructed by hydrogen bonding interactions. These complexes have been employed as photocatalysts for the photodegradation of methyl violet (MV) dye. The photocatalytic experiments reveal that amongst all three complexes, the complex 2 exhibits best photocatalytic performance and degrades 92.8% of MV in time span of 100 min. The plausible photocatalytic degradation mechanism have been proposed with the help of trapping experiments and density of states calculations.

Designing and Judd-Ofelt evaluation of versatile luminescent Eu (III) complexes sensitized with β-diketone ligand for multifarious applications.

The present research work entails synthesis of one binary and four ternary red light emitting Eu (III) based complexes with 3-benzylidene-2,4-pentanedione as main ligand and 1,10-phenanthroline, bathophenanthroline, neocuproine and 4,4'-dimethyl-2,2'-bipyridyl as auxiliary ligands. The Metal-Organic framework of the series was elucidated using EDAX, elemental analysis, FT-IR and 1 H-NMR. This Eu (III) series exhibit optimum thermal stability making them a promising candidate for OLED's. On the basis of emission spectra their optical parameters such as non-radiative and radiative decay rate, luminescence decay time, intrinsic quantum efficiency and Judd-Ofelt intensity parameter were determined. The mono-centric luminescence and Judd-Ofelt parameters reveals the non-existence of symmetry around the europium center. CIE chromaticity coordinates, CCT values, color purity and asymmetric ratios authenticate the color coordinates of complexes in red region. Optical band gap values lies within wide band gap semiconductors range revealing their utilization in military radars, biological labeling.

How to get deeper insights into the optical properties of lanthanide systems: a computational protocol from ligand to complexes

Abstract Theoretical calculations are proving as an essential tool to understand luminescence processes even for systems including lanthanide (Ln3+) ions. As such, the aim of this study is that of presenting a general and comprehensive theoretical protocol based on DFT calculations to rationalize and possibly drive the design of new luminescent Ln3+ complexes through the ab initio determination of the electronic properties of a ligand and two Eu3+ complexes. Different theoretical methodologies have been combined to look into the excited state energies, the luminescence quantum yield, and the energy transfer processes. The protocol has been validated for a β-diketone ligand and two Eu3+ complexes, which contain, in addition to the main ligand, ethanol or triphenylphosphine oxide. Moreover, by starting from the geometry optimization up to the estimation of the ligands’ singlet and triplet lowest energy states, theoretical results quantitatively agree with luminescence experimental parameters, providing at the same time insights into the different energy transfer processes. The different quantum yields of the two complexes have been correctly reproduced.

Synthesis, crystal structures and magnetic properties of Pyrazole-Carboxylic acid complexes

Three new complexes, {[Ni2(3-PCA)2(DMAP)4(H2O)2]·2H2O}2, [Cu2(3-PCA)2(4-PP)2·2H2O]n, and [Cu2(4-PCA)2(2,2′-bpy)2·2H2O]n, are synthesized by the solvothermal method with pyrazole-3-carboxylic acid or pyrazole-4-carboxylic acid as the main ligands and 2,2′-bipyridine, 4-dimethylaminopyridine, or 4-phenylpyridine as auxiliary ligands. The crystal structures of the three complexes are determined by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis, and Fourier transform infrared analysis. The magnetic detection proves that the three complexes are all antiferromagnetic.

Determining antitumor responses to variable cadherin expression

Abstract Cancer immunotherapy has dramatically transformed the treatment of many cancers. Despite this, several limitations exist. For example, in some patients’ cancer can become resistant to immunotherapy and relapse is common. Therefore, it is essential to identify new targets for intervention. Our laboratory previously showed that KLRG1, which has two main ligands E-cadherin and N-cadherin, is a potential target. However, cadherin has many roles including a role in epithelial mesenchymal transition. To examine the KLRG1-cadherin axis in antitumor responses we used CRISPR/Cas9 and retroviral overexpression methods to develop a library of B16–F10 melanoma and 4T1 breast cancer cell lines with variable cadherin expression. The appropriate expression of E- and N-cadherin on the cells in this library was confirmed by both flow cytometry and Western blot. We then demonstrated that the modulation of cadherins does not alter cell proliferation rates in vitro. Importantly, in both models, we find that E-cadherin expressing cell lines cause significantly more mortality than E-cadherin deficient parental cell lines. Together, these findings suggest that the KLRG1-cadherin axis play an important role in antitumor responses. This work was supported by the NIH research Grant R01 AI46709 (L.B.)

Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade.

The epidermal growth factor receptor (EGFR) signaling pathway is one of the main pathways responsible for propagating the luteinizing hormone (LH) signal throughout the cumulus cells and the oocyte. Recently, we have proposed the C-C motif chemokine receptor 2 (CCR2) and its main ligand (monocyte chemoattractant protein-1, MCP1) as novel mediators of the ovulatory cascade. Our previous results demonstrate that the gonadotropins (GNT), amphiregulin (AREG), and prostaglandin E2 (PGE2) stimulation of periovulatory gene mRNA levels occurs, at least in part, through the CCR2/MCP1 pathway, proposing the CCR2 receptor as a novel mediator of the ovulatory cascade in a feline model. For that purpose, feline cumulus-oocyte complexes (COCs) were cultured in the presence or absence of an EGFR inhibitor, recombinant chemokine MCP1, and gonadotropins [as an inducer of cumulus-oocyte expansion (C-OE), and oocyte maturation] to further assess the mRNA expression of periovulatory key genes, C-OE, oocyte nuclear maturation, and steroid hormone production. We observed that MCP1 was able to revert the inhibition of AREG mRNA expression by an EGFR inhibitor within the feline COC. In accordance, the confocal analysis showed that the GNT-stimulated hyaluronic acid (HA) synthesis, blocked by the EGFR inhibitor, was recovered by the addition of recombinant MCP1 in the C-OE culture media. Also, MCP1 was able to revert the inhibition of progesterone (P4) production by EGFR inhibitor in the C-OE culture media. Regarding oocyte nuclear maturation, recombinant MCP1 could also revert the inhibition triggered by the EGFR inhibitor, leading to a recovery in the percentage of metaphase II (MII)-stage oocytes. In conclusion, our results confirm the chemokine receptor CCR2 as a novel intermediate in the ovulatory cascade and demonstrate that the EGFR/AREG and the CCR2/MCP1 signaling pathways play critical roles in regulating feline C-OE and oocyte nuclear maturation, with CCR2/MCP1 signaling pathway being downstream EGFR/AREG pathway within the ovulatory cascade.

Spectroscopic features of Sm3+ complexes based on β-ketoester functionalized ligand for advanced optoelectronic applications

Five samarium complexes are synthesized with main ligand ethyl(4-methylbenzoyl) acetate (EMB) and secondary ligands 4,4′-dimethyl-2,2′-bipyridyl; 2,2′-bipyridyl; 1,10-phenanthroline and bathophenanthroline. The synthesized complexes are investigated by employing different techniques, including elemental analysis, EDX, FT-IR, NMR, TG/DTG, DR, and UV–vis absorption spectroscopy. The investigation of optical features of complexes helps to analyze their photoluminescent features. The characteristic peaks of samarium complexes under excitation of UV light are positioned at 568, 605, 650, and 693nm, and the peak responsible for vermilion emission is located at 605nm which is an intense one. Further, chromaticity coordinates, color purity, and correlated color temperature are calculated to explore vermilion color and the nature of the light of complexes. The decay curve, HOMO-LUMO energy gap, refractive index, and energy transfer mechanism are also discussed in present work.

A theoretical study of a series of iridium complexes with methyl or nitro-substituted 2-(4-fluorophenyl)pyridine ligands with the low-efficiency roll-off performance

A series metal iridium complexes were calculated using the method of DFT and TD-DFT under Gaussian 09 software. H atoms on the N counter in 2-(4-fluorophenyl)pyridine were replaced with methyl and nitro groups, respectively, to obtain two main ligands CFM(2-(4-fluorobrobenyl)-4-methylpyridine) and CFN(2-(4-fluorobrobenyl)-4-nitropyridine), then we obtained six complexes: (CFM)2Ir(acac), (CFM)2Ir(tpip), (CFM)3Ir, (CFN)2Ir(acac), (CFN)2Ir(tpip) and (CFN)3Ir, Where acac is represented as pentane-2, 4-dione, tpip as tetraphenylimido-diphosphinate. The electronic structure, the lowest singlet absorption, the triple excited states as well as the emission spectrum are also theoretically studied.

Copper and Nickel Complexes of Oxamate−Phenol Containing Ligands: A Structural Dichotomy in Oxidized Species

AbstractThe copper and nickel complexes of two tetradentate ligands derived from bis(aminophenol) and bis(phenol) architectures connected by an oxamate linker were isolated. Depending on the metal and ligand, the complex is isolated with either an intact (deprotonated) ligand (12−), one‐electron oxidized ligand (2−) or quinone form (3). Surprisingly, the Mannich base is easier to oxidize than the amidophenol derivatives. The complexes were characterized by X‐ray diffraction, cyclic voltammetry, UV‐Vis‐NIR and EPR spectroscopies. Complex 1 shows two reversible oxidation waves assigned to the successive iminosemiquinone/aminophenolate redox systems. Complex 2− shows an intense NIR feature, as well as an EPR signal at giso=2.043, consistent with a metallic contribution to the main ligand radical SOMO. Complex 3 shows the typical feature of an isolated Cu(II) complex. Spectro‐electrochemistry coupled to DFT calculations demonstrate a ligand‐centered oxidative redox chemistry for all the complexes.

Design of new reversible and selective inhibitors of monoamine oxidase A and a comparison with drugs already approved

BackgroundMonoamine oxidase (MAO) is an enzyme that has been targeted pharmacologically for the treatment of depression and neurodegenerative diseases such as Parkinson's disease. To avoid side effects, drugs currently in use must selectively target either of the enzyme's two isoforms, A or B. In this study, we designed molecules derived from chalcone as potential reversible and selective inhibitors of isoform A of the MAO enzyme.ResultsTen thousand one hundred compounds were designed and screened using molecular docking, considering the pharmacokinetic processes of chemical absorption, distribution, metabolism, and excretion. Density functional theory calculations were performed for the main ligands to evaluate their reactivity. Six drugs qualified as reversible and irreversible inhibitors of both isoform A and isoform B. Among these, molecule 356 was found to be a reversible inhibitor with the best performance in selectively targeting isoform A of the MAO enzyme. The interaction stability of ligand 356 in the isoform A binding site was confirmed by molecular dynamics. One hydrogen bond was found between the ligand and the cofactor, and up to six hydrogen bonds were formed between the ligand and the protein.ConclusionsWe selected a drug model (molecule 356) for its high affinity to isoform A over isoform B of the MAO enzyme. This proposal should decrease experimental costs in drug testing for neurodegenerative diseases. Therefore, our silico design of a reversible inhibitor of isoform A of enzyme monoamine oxidase can be used in further experimental designs of novel drugs with minimal side effects.Graphical

Stereochemical Properties of Two Schiff-Base Transition Metal Complexes and Their Ligand by Using Multiple Chiroptical Spectroscopic Tools and DFT Calculations.

Two transition metal complexes were synthesized with Ni(II) and Cu(II) using a tetradentate Schiff-base ligand, (R,R) and (S,S)-N,N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine. The stereochemical properties of the ligand and the metal complexes were investigated using a combined experimental and theoretical approach. Multiple spectroscopic techniques, which include IR, vibrational circular dichroism (VCD), UV-Vis and electronic circular dichroism (ECD), as well as Raman and the newly discovered ECD-circularly polarized Raman (i.e., eCP-Raman) spectroscopies were utilized. The good agreement achieved between the experimental and simulated IR, VCD, UV-Vis and ECD spectra of the ligand allowed one to identify the presence of three main ligand conformers in solution, thanks, especially to the high VCD sensitivity to the conformations associated with the tertbutyl groups. The helicity of the metal complexes was identified to be M and P for those with the (R,R) and (S,S) ligands, respectively. Furthermore, eCP-Raman measurements were carried out for the two metal complexes under (near) resonance. Their induced solvent chiral Raman features were explained, and the potential application of eCP-Raman was discussed.

Exploration of Optical and Radiative Properties of Fluorinated β-keto Carboxylate Tb3+ Complexes Emanating Cool Green Light.

Tb3+ complexes with β-ketocarboxylic acid as main ligand and heterocyclic systems as auxiliary ligand were synthesized and analyzed to assess their prospective relevance as green light emitting material. The complexes were characterized via various spectroscopic techniques and were found to be stable up to ≈ 200 ℃. Photoluminescent (PL) investigation was performed to assess the emissive nature of complexes. Longest luminescence time of decay (1.34ms) and highest intrinsic quantum efficiency (63.05%) were fetched for complex T5. Color purity of complexes was found to be in range 97.1 - 99.8% which demonstrated the aptness of these complexes in green color display devices. NIR Absorption spectra were employed to evaluate Judd-Ofelt parameters to appraise the luminous performance and environment encircling Tb3+ ions. The JO parameters were found to follow the order: Ω2 > Ω4 > Ω6 and suggested the higher covalence character in complexes. Theoretical branching ratio in the range 65.32 - 72.68%, large stimulated emission cross section and narrow FWHM for 5D4 → 7F5 transition unlocked the relevance of these complexes as a green color laser media. Band gap and Urbach analysis were consummated via enforcing nonlinear curve fit function on absorption data. Two band gaps with values in between 2.02 - 2.93eV established the prospective use of complexes in photovoltaic devices. Energies of HOMO and LUMO were estimated employing geometrically optimized structures of complexes. Investigation of biological properties accomplished via antioxidant and antimicrobial assays which communicated their applicability in biomedical domain.

Computational and optoelectronic quantification of semi-conducting, warm ruby red color emanating Eu3+ complexes with hetro-cyclic ligands.

Six Eu3+ complexes were synthesised with β-keto acid as main ligand and secondary ligands through liquid assisted grinding method. These complexes were characterised by various techniques such as spectroscopic technique, XRD, EDAX, SEM analysis, thermal technique, Urbach energy and optical band gap investigation. The luminous photophysical properties were studied by PL spectroscopy in solid as well as solution phase and some theoretical calculation was done to investigate the radiative (Arad) & non-radiative (Anrad) transition rate, quantum efficiency (ɸ), Judd Ofelt parameters for 5D0 → 7F2,4 transitions in both states. Judd Ofelt parameters were also calculated by the JOES software and the outcomes are well harmonised with theoretical values. The complexes have CIE color coordinate value in ruby red region and above 88.65% color purity in both phases, which made them attractive candidates for red light-emitting displays. 5D0 → 7F2 transition was proposed as a laser emission transition owing to their high branching ratio (67.18-74.24%) in solid and (60.09-74.40%) in solution phase. Computational methods were employed to determine the structure and energy of various molecular orbitals. Antimicrobial assay of complexes was also rationalised and found that the complexes are pertinent as good bactericidal and fungicidal agents in pharmaceutical industry.

Novel deep red to near-infrared phosphorescent iridium(III) complexes bearing pyrenyl: Syntheses, structures and modulation of the photophysical properties

The extension of π-conjugation and the introduction of substituents are efficient channel for achieving low-energy emitting phosphors. To investigate the influence of substituent effect on the deep-red or near-infrared iridium(III) complexes containing great π-conjugation cyclometalating ligands, we synthesized four pyrenyl-based heteroleptic Ir(III) complexes bearing electron-withdrawing or -donating groups. The four Ir(III) complexes comprise 5-R-2-(1-pyrenyl)pyridine (R = H, CF3, F, CH3) as the main ligands and 2,2,6,6-tetramethyl-heptane-3,5-dione as ancillary ligands. Their structures and coordination geometries are determined by single crystal X-ray diffraction. It is found that the emission profiles of four complexes are located on deep red to near-infrared region and -CF3 substitution leads to a bathochromic shift of 11 nm relative to the unsubstituted complex. From density functional theory calculation results as well as electrochemical analysis, their HOMO and LUMO energy levels fall in the order of substituents -CF3 < -F < -H < -CH3. Intriguingly, the electron density distributions of LUMOs of both -CF3 and -CH3 substituted complexes are more susceptible than their HOMOs, while the HOMO of the -F substituted complex is more susceptible. Our work showcases the vital significance of substituent effect on modulating the electronic structure of deep-red or near-infrared iridium complexes cyclometalated by great π-conjugation cyclometalating ligands.

TGF-Beta Induces Activin A Production in Dermal Fibroblasts Derived from Patients with Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a catastrophic, ultra-rare disease of heterotopic ossification caused by genetic defects in the ACVR1 gene. The mutant ACVR1 receptor, when triggered by an inflammatory process, leads to heterotopic ossification of the muscles and ligaments. Activin A has been discovered as the main osteogenic ligand of the FOP ACVR1 receptor. However, the source of Activin A itself and the trigger of its production in FOP individuals have remained elusive. We used primary dermal fibroblasts from five FOP patients to investigate Activin A production and how this is influenced by inflammatory cytokines in FOP. FOP fibroblasts showed elevated Activin A production compared to healthy controls, both in standard culture and osteogenic transdifferentiation conditions. We discovered TGFβ1 to be an FOP-specific stimulant of Activin A, shown by the upregulation of the INHBA gene and protein expression. Activin A and TGFβ1 were both induced by BMP4 in FOP and control fibroblasts. Treatment with TNFα and IL6 produced negligible levels of Activin A and TGFβ1 in both cell groups. We present for the first time TGFβ1 as a triggering factor of Activin A production in FOP. As TGFβ1 can promote the induction of the main driver of FOP, TGFβ1 could also be considered a possible therapeutic target in FOP treatment.

Role of Hyaluronic Acid in Selected Malignant Neoplasms in Women

Hyaluronic acid (HA) is a significant glycosaminoglycan component of the extracellular matrix, playing an essential role in cell localization and proliferation. However, high levels of HA may also correlate with multidrug resistance of tumor cells, an increased tendency to metastasize, or cancer progression, and thus represent a very unfavorable prognosis for cancer patients. The purpose of this review article is to summarize the results of studies describing the relationship between HA, the main ligand of the CD44 receptor, or other components of the HA signaling pathway. In addition, we review the course of selected female malignancies, i.e., breast, cervical, endometrial, and ovarian cancer, with the main focus on the mechanisms oriented to CD44. We also analyze reports on the beneficial use of HA-containing preparations in adjuvant therapy among patients with these types of cancer. Data from the literature suggest that HA and its family members may be critical prognostic biomarkers of selected malignancies among women. Nevertheless, the results of the available studies are inconclusive, and the actual clinical significance of HA expression analysis is still quite enigmatic. In our opinion, the HA-CD44 signaling pathway should be an attractive target for future research related to targeted therapy in gynecological cancers.

Fluorescent sensor array for tetracyclines discrimination using a single Dye@MOF composite sensor

The incorporation of multiple sensing elements to a single sensor has been proposed by our group as an improvement for the array sensing technique with retaining the high selectivity of traditional multi-sensor based sensor array but largely simplifying the analytical operation. How to select reasonable sensing elements to construct the sensor is the key to improve the analytical performance. Herein, we propose a concept to solve this issue, that is, using the components which test different properties of analytes to discriminate them from various aspects. As a proof-of-principle trial, a MOF based composite sensor was designed to analyze tetracycline type antibiotics. The porphyrin-containing main ligand, naphthyl auxiliary ligand and rhodamine B guest were installed to response to the redox property, adsorption affinity and absorption/exchanging capability of the analyte, respectively. Six tetracycline homologous were clearly identified by this sensor, and it also exhibited good quantification performance. This method was successfully applied to the analysis of practical milk sample.

Synthesis and DFT supported spectroscopic characterization of a pyrazolone Schiff base complex of RuII-NO core

Due to the fact of fascinating properties of 4-aminoantipyrene and other pyrazolone derivatives, this work is mainly focused on the synthesis of Schiff base complex of Ru-NO core containing pyrazolone as the main ligand functionality. Several spectroscopic and spectrometric techniques in association with theoretical approach (DFT) have been applied to elucidate the structure of the complex. In addition to the characterization, parameters that decide to label the given compound as a significant nitric oxide releasing molecule (NORM) have been discussed. DFT based computational studies using LANL2DZ/B3LYP and 6-31 G(d,p)/B3LYP formalism, respectively for Ru and nonmetallic atoms of the complex have been used to deal with the NO-releasing phenomenon. From the results discussed herein it is evident that the complex can release NO at the cost of low energy radiation.

Gas6/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients.

Gas6 (growth arrest-specific gene 6) is a widely expressed vitamin K-dependent protein that is involved in many biological processes such as homeostatic regulation, inflammation and repair/fibrotic processes. It is known that it is the main ligand of TAMs, a tyrosine kinase receptor family of three members, namely MerTK, Tyro-3 and Axl, for which it displays the highest affinity. Gas6/TAM axis activation is known to be involved in modulating inflammatory responses as well as fibrotic evolution in many different pathological conditions. Due to the rapidly evolving COVID-19 pandemic, this review will focus on Gas6/TAM axis activation in SARS-CoV-2 infection, where de-regulated inflammatory responses and fibrosis represent a relevant feature of severe disease manifestation. Furthermore, this review will highlight the most recent scientific evidence supporting an unsuspected role of Axl as a SARS-CoV-2 infection driver, and the potential therapeutic advantages of the use of existing Axl inhibitors in COVID-19 management. From a physiological point of view, the Gas6/TAM axis plays a dual role, fostering the tissue repair processes or leading to organ damage and loss of function, depending on the prevalence of its anti-inflammatory or profibrotic properties. This review makes a strong case for further research focusing on the Gas6/TAM axis as a pharmacological target to manage different disease conditions, such as chronic fibrosis or COVID-19.

Research on PAR-1 in Cancer, Cardiovascular Disease and Nerve-related Diseases

PAR-1 (protein kinase receptor 1, also known as thrombin receptor) is a member of the G protein-coupled receptor family, and its main ligand is thrombin. PAR-1 is mainly expressed in platelets, endothelial cells, smooth muscle cells and some neural cells, involved in hemostasis and atherosclerosis formation. At present, a great deal of research has also confirmed that PAR-1 is involved in epithelial-to-mesenchymal transition and epithelial-to-endothelial transformation; PAR-1 can regulate the NF-κB pathway, stimulate the formation of tumor angiogenesis, and participate in the development of tumors through a variety of ways. At the same time, the blood state of tumor patients often presents a hypercoagulable state. As one of the thrombin receptors, PAR-1 may participate in the formation of hypercoagulable state in tumor patients. The review focuses on the expression and activation mechanism of PAR-1 and its physiological pathological process; And how to participate in the occurrence and development of tumors and the relationship with cardiovascular diseases. The aim is to point out that PAR-1 may be a potential target for tumor therapy and may be helpful to improve the hypercoagulable state and prolong the survival of patients with advanced cancer.