Class Of Ligands Research Articles

DESIGN, SYNTHESIS AND BIOLOGICAL PROPERTIES OF TRANSITION METAL COMPLEXES OF SCHIFF BASE LIGAND DERIVED FROM PYRIDINE DERIVATIVES

Novel classes of heterocyclic Schiff base ligand were prepared from the condensation of 2-methoxy benzaldehyde and 2-amino 4-methyl pyridine in absolute ethanol in presence of catalytic amount of dilute HCl. The resulted novel class ofheterocyclic ligand was treated with metal salt or acetate results in the formation of Fe (III), Co (III), Ni (II) & Cu (II)complexes. All newly synthesized resulted ligand its metal complexes were characterized by elemental analysis and FTIR,Magnetic susceptibility, Antimicrobial, Antioxidant, ESR spectrum for Copper complex in DMF solvent recorded atroom temperature. The Electronic spectra and magnetic susceptibility measurements indicates that square planer andoctahedral geometry of these complexes also suggest their structure in which (N, O) group acts as bidentate ligand. Thethermal stability, decomposition behavior has been investigated by using thermo gravimetric analysis at heating rate 10°Cper minute with nitrogen atmosphere and their and kinetic parameter was also calculated by using Freeman Carrollmethod. Screening results of antimicrobial, antioxidant activity of transition metal complexes shows good antibacterialand antifungal activity and excellent antioxidant activity.

Polymer N-Heterocyclic Carbene (NHC) Ligands for Silver Nanoparticles.

Polymer N-heterocyclic carbenes (NHCs) are a class of robust surface ligands to provide superior colloidal stability for metal nanoparticles (NPs) under various harsh conditions. We report a general method to prepare polymeric NHCs and demonstrate that these polymer NHC-AgNPs are stable against oxidative etching and show high peroxidase activity. We prepared three imidazolium-terminated poly(methyl methacrylate) (PMMA), polystyrene (PS), and poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA) through atom-transfer radical polymerization with an imidazole-containing initiator. The imidazolium end group was further converted to NHC-Ag(I) in the presence of Ag2O at room temperature. Polymer NHC-Ag(I) can transmetalate to AgNPs through ligand exchange at the interface of oil/water within 2 min. All the three polymers can modify metal NPs, such as AgNPs, Ag nanowires, and AuNPs, providing excellent thermal, oxidative, and chemical stabilities for AgNPs. As an example, in the presence of hydrogen peroxide, AgNPs modified by polymer NHCs were resistant against oxidative etching with a rate of ∼700 times slower than those grafted with thiolates. AgNPs modified by polymer NHCs also showed higher peroxidase activity, 4 times more active than those capped by citrate and polyvinylpyrrolidone (PVP) and 2 times more active than those with polymer thiolate. Our studies demonstrate a great potential of using polymer NHCs to stabilize metallic NPs for various applications.

Relating protein crystal structure to ligand-binding thermodynamics.

An important interface between biophysical chemistry and biological crystal structures involves whether it is possible to relate experimental calorimetry measurements of protein ligand binding to 3D structures. This has proved to be challenging. The probes of the structure of matter, namely X-rays, neutrons and electrons, have challenges of one type or another in their use. This article focuses on saccharide binding to lectins as a theme, yet after 25 years or so it is still a work in progress to connect 3D structure to binding energies. Whilst this study involved one type of protein (lectins) and one class of ligand (monosaccharides), i.e. it was specific, it was of general importance, as measured for instance by its wide impact. The impetus for writing this update now, as a Scientific Comment, is that a breakthrough in neutron crystal structure determinations of saccharide-bound lectins has been achieved. It is suggested here that this new research from neutron protein crystallography could improve, i.e. reduce, the errors in the estimated binding energies.

What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.

For decades, ibogaine─the main psychoactive alkaloid found in Tabernanthe iboga─has been investigated as a possible treatment for substance use disorders (SUDs) due to its purported ability to interrupt the addictive properties of multiple drugs of abuse. Of the numerous pharmacological actions of ibogaine and its derivatives, the inhibition of α3β4 nicotinic acetylcholine receptors (nAChRs), represents a probable mechanism of action for their apparent anti-addictive activity. In this Perspective, we examine several classes of compounds that have been discovered and developed to target α3β4 nAChRs. Specifically, by focusing on compounds that have proven efficacious in pre-clinical models of drug abuse and have been evaluated clinically, we highlight the promising potential of the α3β4 nAChRs as viable targets to treat a wide array of SUDs. Additionally, we discuss the challenges faced by the existing classes of α3β4 nAChR ligands that must be overcome to develop them into therapeutic treatments.

One-step synthesis of bisphosphine monoxide ligands via PdI2-catalysed oxidation

Bisphosphine monoxides are an emerging class of monophosphine ligands that have found their use in many enantioselective protocols, especially in the field of asymmetric C-H functionalization, yet their synthesis is usually multistep and chemically-wasteful. This report shows a one-step modified protocol based on Grushin’s mono-oxidation of axially chiral bisphosphine ligands to form axially chiral bisphosphine monoxide ligands with biphenyl and 1,1’-binaphthyl scaffolds, by changing the reaction conditions as well as careful monitoring of the reaction progress by NMR spectroscopy. The modified protocol provides a quick way to prepare a series of chiral bisphosphine monoxide ligands for ligand screening in asymmetric methodological researches.

Versatile Synthesis of Trisphosphines Bearing Phenylene and Vinylene Backbones Useful for Metal Catalysis and Materials Applications

AbstractTrisphosphines, in which two phenylene or vinylene backbones connect three phosphine atoms, belong to an emerging class of ligands in metal-catalyzed organic synthesis and materials applications. However, these ligands were previously known only in a small variety because of the synthetic limitations. We report herein two versatile synthetic routes to a hitherto unavailable variety of trisphosphines. The compounds bearing phenylene backbones were synthesized by sequential addition of two different organolithium reagents to triphenyl phosphite and that with vinylene backbones by stereoretentive addition of lithium diarylphosphide to a cis-bromoalkene. The new trisphosphine compounds will serve as valuable tools for the development of transition-metal-catalyzed reactions and functional materials.

Genetically Encoded Phosphine Ligand for Metalloprotein Design.

Phosphine ligands are the most important class of ligands for cross-coupling reactions due to their unique electronic and steric properties. However, metalloproteins generally rely on nitrogen, sulfur, or oxygen ligands. Here, we report the genetic incorporation of P3BF, which contains a biocompatible borane-protected phosphine, into proteins. This step is followed by a straightforward one-pot strategy to perform deboronation and palladium coordination in aqueous and aerobic conditions. The genetically encoded phosphine ligand P3BF should significantly expand our ability to design functional metalloproteins.

Chiral Ligands Based on Binaphthyl Scaffolds for Pd-Catalyzed Enantioselective C-H Activation/Cycloaddition Reactions.

We report the first examples of the use of a new class of ligands (NOBINAc) for performing asymmetric C-H activations using palladium catalysts. These ligands combine the axial chirality of binaphthyl scaffolds with the bifunctional and bidentate coordination properties of mono-N-protected amino acids (MPAAs), which are well-known to favor Pd-promoted C-H activations via concerted metalation-deprotonation mechanisms. We demonstrate that our new ligands enable substantially higher enantioselectivities than MPAAs in the assembly of 2-benzazepines through formal (5 + 2) cycloadditions between homobenzyltriflamides or o-methylbenzyltriflamides and allenes.

Di(2-picolyl)amines as Modular and Robust Ligands for Nickel-Catalyzed C(sp2)-C(sp3) Cross-Electrophile Coupling.

Ni-catalyzed aryl-alkyl coupling reactions are reliant on using a limited set of commercially available bidentate nitrogenous ligands to enable the reaction, because noncommercial analogues usually entail challenging syntheses. In this work, di(2-picolyl)amines (DPAs) are explored as an alternative modular ligand class for the nickel-catalyzed aryl-alkyl cross-electrophile coupling. Novel DPA ligands were synthesized directly from inexpensive amine and pyridine building blocks in a single step. This facile synthetic route enabled the parallel synthesis of DPA ligands with varied steric and electronic properties. From this collection of ligands, a few robust ligands for C(sp2)-C(sp3) cross-electrophile coupling were identified and tested in the cross-coupling of a range of diverse molecules, including model examples for late-stage functionalization.

The Role of the Aryl Hydrocarbon Receptor (AhR) and Its Ligands in Breast Cancer.

Breast cancer is a complex disease which is defined by numerous cellular and molecular markers that can be used to develop more targeted and successful therapies. The aryl hydrocarbon receptor (AhR) is overexpressed in many breast tumor sub-types, including estrogen receptor -positive (ER+) tumors; however, the prognostic value of the AhR for breast cancer patient survival is not consistent between studies. Moreover, the functional role of the AhR in various breast cancer cell lines is also variable and exhibits both tumor promoter- and tumor suppressor- like activity and the AhR is expressed in both ER-positive and ER-negative cells/tumors. There is strong evidence demonstrating inhibitory AhR-Rα crosstalk where various AhR ligands induce ER degradation. It has also been reported that different structural classes of AhR ligands, including halogenated aromatics, polynuclear aromatics, synthetic drugs and other pharmaceuticals, health promoting phytochemical-derived natural products and endogenous AhR-active compounds inhibit one or more of breast cancer cell proliferation, survival, migration/invasion, and metastasis. AhR-dependent mechanisms for the inhibition of breast cancer by AhR agonists are variable and include the downregulation of multiple genes/gene products such as CXCR4, MMPs, CXCL12, SOX4 and the modulation of microRNA levels. Some AhR ligands, such as aminoflavone, have been investigated in clinical trials for their anticancer activity against breast cancer. In contrast, several publications have reported that AhR agonists and antagonists enhance and inhibit mammary carcinogenesis, respectively, and differences between the anticancer activities of AhR agonists in breast cancer may be due in part to cell context and ligand structure. However, there are reports showing that the same AhR ligand in the same breast cancer cell line gives opposite results. These differences need to be resolved in order to further develop and take advantage of promising agents that inhibit mammary carcinogenesis by targeting the AhR.

12-Vertex closo-3,1,2-Ruthenadicarbadodecaboranes with Chelate POP-Ligands: Synthesis, X-ray Study and Electrochemical Properties

A class of so-called POP ligands (Xanthos, NiXantphos, DPEphos) are of a great interest to the coordination chemistry due to their wide P-M-P bite angles and ability to show either κ2- or κ3-binding modes. Such κ2–κ3-rearrangement is valuable for catalytic application and internal stabilization of intermediates. To widen the scope of ruthenium-based catalysts for Atom Transfer Radical Polymerization (ATRP) two new approaches to the synthesis of closo-ruthenacarboranes with aforementioned POP ligands were developed and six new 17-e (3,3-(POP)-3-Cl-closo-3,1,2-RuC2B9H11; 2, 4, 7) and 18-e (3,3-(POP)-3-NCCH3-closo-3,1,2-RuC2B9H11; 3, 5, 8) clusters were synthesized and characterized by means of NMR or ESR spectroscopy, MALDI mass-spectrometry and single crystal X-ray diffraction studies. The unique 18-e complex of Ru(II) with dioxygen ligand 3,3-(DPEphos)-3-(η2-O2)-closo-3,1,2-RuC2B9H11 (9) was isolated and characterized by X-ray diffraction. It was shown that aforementioned POP ligands coordinate to ruthenium by two phosphorus atoms in a κ2-fashion. The performed electrochemical studies have shown reversible Ru(II)-Ru(III) transition making the complexes suitable for application in catalysis of polymerization. The test experiments on methyl methacrylate (MMA) polymerization indicate the proceeding of the process in according with an ATRP mechanism.

Computational Insights on Periodicity in Bonding and Lewis Acidity and Basicity of the p‐Block Trispyrazolylborate Complexes

AbstractHydrotris(pyrazolyl)borate ligands are a popular class of ligands to stabilize both Lewis acidic and Lewis basic main group compounds. In this work we analyze the low‐valent group 13–15 compounds of hydrotris(3,5‐dimethyl‐pyrazolyl)borate ligand, [Tp*E]x, 1–15 (E=group 13 element, x=0; E=group 14 element, x=1+ ; E=group 15 element, x=2+) based on density functional theory. A periodic increment in intrinsic Lewis acidity is observed down the group due to increased E−N bond polarization towards nitrogen, resulting in lower energy secondary binding sites. However, global Lewis acidity measures in terms of FIA and IIA indicate the dependency on the choice of the nucleophile. In general, this study underscores the potential of the Tp* ligand in stabilizing the reactive low‐valent p‐block elements.

Seasonal dissolved copper speciation in the Strait of Georgia, British Columbia, Canada

The Strait of Georgia (SoG) is a semi-enclosed, urban basin with seasonally dependent estuarine water circulation, dominantly influenced by Northeast Pacific waters and the Fraser River. To establish a baseline and understand the fate and potential toxicity of Cu in the SoG, we determined seasonal and spatial depth profiles of dissolved Cu (dCu) speciation, leading to estimates of the free hydrated copper (Cu2+) concentrations, as a proxy for Cu toxicity. The concentration of dCu was largely controlled by conservative mixing of the ocean and freshwater endmembers in the SoG. In all samples, ligand concentrations exceeded dCu, by a ratio greater than 1.5, resulting in the complexation of 99.98% of the dCu by strong binding organic ligands. The concentrations of Cu2+ were less than 10-13.2 M, significantly lower than the well-established Cu toxicity threshold (10-12 M Cu2+) for microorganisms. Our results indicate that ambient Cu-binding ligands effectively buffer Cu2+ concentrations within the Strait of Georgia, posing no threat to marine life. In almost 90% of the samples, the ligands were best classified as a single ligand class, with a logKCuL,Cu2+cond between 12.5 and 14.1. The concentrations of these single class ligands were greatest in warm, low salinity, nutrient depleted waters, suggesting that either terrestrially sourced ligands dominate dCu speciation in the SoG, or freshwater sources in the SoG establish the conditions that promote the production of Cu binding ligands in its surface waters. The remaining 10% of the samples were from the euphotic zone, where we detected a stronger ligand class, L1, of logKCuL1,Cu2+cond between 13.5 and 14.3, and a weaker ligand class, L2, of logKCuL2,Cu2+cond between 11.5 and 12.3. In these surface samples, logKCuL1,Cu2+cond and logKCuL2,Cu2+cond were positively correlated with temperature, while L2 concentrations were positively correlated with chromophoric dissolved organic matter of terrestrial origin. This study is the first to perform hierarchal clustering of a trace metal speciation dataset and enabled the distinction of 6 clusters across season, depth, and region of the SoG, highlighting the influence of freshwater and open ocean ligand sources, conservative mixing dynamics, and particulate Cu concentrations on dCu speciation within estuarine basins.

Novel synthetic procedures for C2 substituted imidazoquinolines as ligands for the α/β-interface of the GABAA-receptor

A series of substituted imidazoquinolines, a structurally related chemotype to pyrazoloquinolinones, a well-known class of GABAA ligands, was prepared via two synthetic procedures and the efficiency of these procedures were compared. One method relies on classical heterocyclic synthesis, the other one aims at late-stage decoration of a truncated scaffold via direct C–H functionalization. A pharmacological evaluation disclosed that one of the synthesized derivatives showed interesting activity on a α1β3 containing receptor subtype.Graphical abstract

One class classification for the detection of β2 adrenergic receptor agonists using single-ligand dynamic interaction data

G protein-coupled receptors are involved in many biological processes, relaying the extracellular signal inside the cell. Signaling is regulated by the interactions between receptors and their ligands, it can be stimulated by agonists, or inhibited by antagonists or inverse agonists. The development of a new drug targeting a member of this family requires to take into account the pharmacological profile of the designed ligands in order to elicit the desired response. The structure-based virtual screening of chemical libraries may prioritize a specific class of ligands by combining docking results and ligand binding information provided by crystallographic structures. The performance of the method depends on the relevance of the structural data, in particular the conformation of the targeted site, the binding mode of the reference ligand, and the approach used to compare the interactions formed by the docked ligand with those formed by the reference ligand in the crystallographic structure. Here, we propose a new method based on the conformational dynamics of a single protein–ligand reference complex to improve the biased selection of ligands with specific pharmacological properties in a structure-based virtual screening exercise. Interactions patterns between a reference agonist and the receptor, here exemplified on the β2 adrenergic receptor, were extracted from molecular dynamics simulations of the agonist/receptor complex and encoded in graphs used to train a one-class machine learning classifier. Different conditions were tested: low to high affinity agonists, varying simulation duration, considering or ignoring hydrophobic contacts, and tuning of the classifier parametrization. The best models applied to post-process raw data from retrospective virtual screening obtained by docking of test libraries effectively filtered out irrelevant poses, discarding inactive and non-agonist ligands while identifying agonists. Taken together, our results suggest that consistency of the binding mode during the simulation is a key to the success of the method.

Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor-Like Model of Retinal Degeneration.

The 18 kDa translocator protein (TSPO) is predominantly located in the mitochondrial outer membrane, playing an important role in steroidogenesis, inflammation, survival, and cell proliferation. Its expression in the CNS, and mainly in glial cells, is upregulated in neuropathologies and brain injury. In this study, the potential of targeting TSPO for the therapeutic treatment of inflammatory-based retinal neurodegeneration was evaluated by means of an in vitro model of lipopolysaccharide (LPS)-induced degeneration in 661 W cells, a photoreceptor-like cell line. After the assessment of the expression of TSPO in 661W cells, which, to the best of our knowledge, was never investigated so far, the anti-inflammatory and cytoprotective effects of a number of known TSPO ligands, belonging to the class of N,N-dialkyl-2-arylindol-3-ylglyoxylamides (PIGAs), were evaluated, using the classic TSPO ligand PK11195 as the reference standard. All tested PIGAs showed the ability to modulate the inflammatory and apoptotic processes in 661 W photoreceptor-like cells and to reduce LPS-driven cellular cytotoxicity. The protective effect of PIGAs was, in all cases, reduced by cotreatment with the pregnenolone synthesis inhibitor SU-10603, suggesting the involvement of neurosteroids in the protective mechanism. As inflammatory processes play a crucial role in the retinal neurodegenerative disease progression toward photoreceptors' death and complete blindness, targeting TSPO might represent a successful strategy to slow down this degenerative process that may lead to the inexorable loss of vision.

Classical vs. Non-Classical Cyclometalated Pt(II) Complexes.

Rollover cyclometalated complexes constitute a family of derivatives which differ from classical cyclometalated species in certain aspects. Various potential application fields have been developed for both classes of compounds, which have both similarities and differences. In order to uncover the relationships and distinctions between these two families of compounds, four Pt(II) cyclometalated complexes derived from 2-phenylpyridine (ppy) and 2,2'-bipyridine (bpy), assumed as prototypical ligands, were compared. For this study, an electron rich isostructural and isoelectronic pair of compounds, [Pt(N^C)Me(PPh3)], and an electron-poorer compound, [Pt(N^C)Cl(PPh3)] were chosen (N^C = ppy or bpy). DFT calculations, cyclic voltammetry, and UV-Vis spectra also helped to shed light into these species. Due to the presence of the more electronegative nitrogen in place of a C-H group, the rollover bpy-H ligand becomes a slightly weaker donor than the classical ppy-H ligand, and hence, generates (slightly) more stable cyclometalated complexes, lower energy frontier molecular orbitals, and electron-poorer platinum centers. On the whole, it was revealed that classical and rollover complexes have overall structural similarity, which contrasts to their somewhat different chemical behavior.

Dinuclear PdII complexes bearing mixed NHC/Py/PPh3 donor set ligands: Catalytic applications and electrochemical investigations

Bimetallic palladium(II) complexes containing classical NHC donor ligands are becoming increasingly popular owing to their various catalytic applications. However, examples of the aforementioned complexes with mixed NHC/PPh3 ligands are still rare. Bimetallic palladium(II) complexes possessing these mixed ligands are described starting from a C2‐symmetric bis‐imidazolium salt containing 4,4′‐substituted central biphenyl ring. All the palladium(II) complexes have been tested as precatalysts in α‐arylation of oxindole and Suzuki–Miyaura coupling reactions. The complex composed of mixed NHC/PPh3 donor ligands shows superior catalytic activity compared with the corresponding PEPPSI type complexes when applied in α‐arylation of oxindole. The dinuclear complexes display better activity compared with the mononuclear complexes. The preliminary electrochemical measurements show the facile oxidation of PdII in the presence of combined NHC/PPh3 ligands compared with a combination of NHC/Py ligands.

Ni-catalyzed, enantioselective three-component radical relayed reductive coupling of alkynes: Synthesis of axially chiral styrenes

Axially chiral styrenes are of great interest because they could serve as a class of novel chiral ligands in enantioselective synthesis. However, only recently have strategies been developed for their enantioselective preparation. Herein, we have developed a Ni-catalyzed, enantioselective, three-component radical relayed reductive coupling to rapidly construct axially chiral styrene. This three-component radical relayed reductive coupling strategy utilizes a chiral nickel/pyridine-oxazoline system to facilitate the challenging three-component, enantioselective difunctionalization of alkynes with high efficiency and excellent enantioselectivity. The mild conditions allow for broad substrate scopes as well as good functional-group toleration. We performed computational mechanistic studies to gain insights into the mechanism and origin of the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be easily transformed into 1-(1-phenylvinyl)naphthalene phosphine ( ( s )-SJTU-PHOS-1 ) with high stereoselectivities, which showed great promise as a new type of styrene ligand. • Three-component radical relayed reductive coupling to construct axial chiral styrene • Broad substrate scope with excellent enantioselectivity and regioselectivity • Axially chiral styrenes transformed into chiral ligand • Computational studies to gain insights into the chemo- and enantioselectivity Axially chiral styrene has recently attracted considerable attention from chemists because of its widespread use in biological active compounds, chiral catalysts, and ligands. In this article, we develop a radical relayed reductive coupling to construct axially chiral styrene with high efficiency and excellent enantioselectivity via highly active sp 2 center radicals. The resulting axially chiral styrenes could be easily transformed into a new type of potential styrene ligand. Mechanistically, we conducted detailed computational mechanistic studies to understand the chemo- and enantioselectivity of this reaction. We anticipate that this enantioselective three-component radical relayed reductive coupling protocol will have important implications for the construction of axially chiral styrene. Zhang and co-workers have developed a novel radical relayed reductive coupling to construct axial chiral styrene with high efficiency. A weak coordination effect, found to be crucial in nickel-catalyzed three-component cross-coupling reactions, is not required in this system. The authors performed computational studies to gain insights into the chemo- and enantioselectivity. Furthermore, the reaction could be scaled up, and the resulting axially chiral styrenes could be transformed into chiral ligand ( s )-SJTU-PHOS-1 , which showed great promise as a new styrene ligand.

Electronic Characterization of Vis-NIR Absorbing Noninnocent Ruthenium Oxyquinolate-merocyanine Complexes and their Photoacoustic Emission in Aqueous Micellar Solution†.

The electronic and photophysical properties for a series of ruthenium(II) polypyridyl dyes are presented where a π-accepting 5-(vinyl-cyanine)-8-oxyquinolate class of ligand is incorporated to yield an improved vis-NIR absorption. A combination of computational, UV-vis-NIR absorption, phosphorescence emission and cyclic voltammetry studies are used to probe the influence of these ligands on complex electronic and photophysical properties. To assess their potential as vis-NIR photoacoustic contrast agents, select complexes were formulated in a PBS buffer/Tween® 20 solvent system. The p-quinolin-1-ium, 1,3,3-trimethyl-3H-indol-1-ium and 1,1,3-trimethyl-1H-benzo[e]indol-3-ium acceptor groups each impart a strong 680 nm optical absorption and photoacoustic emission on par with the performance exhibited by both the methylene blue and cryptocyanine commercial dyes.