Different Types Of Ligands Research Articles

Restricted and Unrestricted Migration Mechanisms of Silica Nanoparticles in Agarose Gels and Their Utilization for the Separation of Binary Mixtures

The migration of SiO2 nanoparticles (NP) was investigated during agarose gel electrophoresis with various gel mesh sizes. As a model system, spherical SiO2 NP of different sizes were synthesized by Stober synthesis, and surface-modified by covalently binding different types of ligands to tailor the zeta potential as required. In the following step, agarose gels were cast with TBE (Tris/Borate/EDTA) buffer solution, thereby controlling the mesh sizes by varying agarose concentration, with higher concentrations leading to smaller mesh sizes. Additionally, the applied voltage could be varied for different electrophoretic experiments. Generally, small mesh sizes and high applied voltages lead to faster particle migration. The migration of SiO2 NP occurs under two regimes: restricted migration, where small mesh size interferes with large particles so that the gel is acting similar to a sieve; and unrestricted migration, where mesh size does not influence the particles’ migration behavior and they move accordin...

Role of Ammonium Derivative Ligands on Optical Properties of CH3NH3PbBr3 Perovskite Nanocrystals.

Amines, ammonium salts, and their combination with organic acids are commonly employed ligands during the synthesis of colloidal perovskite nanocrystals (PNCs). However, the role of surface coordination, derived from different ammonium derivative ligands, on the optical properties of PNCs remains poorly understood. In this study, octylamine (OA), octylammonium bromide (OABr), and oleic acid (OAc) were applied, standing for amine, ammonium salt, and organic acid, respectively. The effects of four different types of ligands, including OA, OABr, OA-OAc, and OABr-OAc, on the surface coordination and subsequently optical properties of CH3NH3PbBr3 PNCs were comparatively investigated. Compared to amine ligand, the ammonium salt could coordinate to both surface cations and anions of PNCs to passivate their surface defects more effectively, leading to enhanced optical properties including higher photoluminescence (PL) spectral intensities and PL quantum yield. Moreover, the combination of OAc with amine rather than ammonium salt ligand could trigger the protonation-deprotonation reaction to further improve their coordination effect on a PNC's surface, thus leading to significantly enhanced optical properties of PNCs. This study clarified the surface coordination of different ammonium derivative ligands and their role on the optical properties of PNCs, which could guide the design of ligands during the synthesis of PNCs.

Tailored Transition‐Metal Coordination Environments in Imidazole‐Modified DNA G‐Quadruplexes

Two types of imidazole ligands were introduced both at the end of tetramolecular and into the loop region of unimolecular DNA G‐quadruplexes. The modified oligonucleotides were shown to complex a range of different transition‐metal cations including NiII, CuII, ZnII and CoII, as indicated by UV/Vis absorption spectroscopy and ion mobility mass spectrometry. Molecular dynamics simulations were performed to obtain structural insight into the investigated systems. Variation of ligand number and position in the loop region of unimolecular sequences derived from the human telomer region (htel) allows for a controlled design of distinct coordination environments with fine‐tuned metal affinities. It is shown that CuII, which is typically square‐planar coordinated, has a higher affinity for systems offering four ligands, whereas NiII prefers G‐quadruplexes with six ligands. Likewise, the positioning of ligands in a square‐planar versus tetrahedral fashion affects binding affinities of CuII and ZnII cations, respectively. Gaining control over ligand arrangement patterns will spur the rational development of transition‐metal‐modified DNAzymes. Furthermore, this method is suited to combine different types of ligands, for example, those typically found in metalloenzymes, inside a single DNA architecture.

Comparative study of 1:1 Lewis acid–base adducts between Cp2M(L)H (M = V, Nb, Ta; L = CO, C2H4, P(CH3)3) and BF3/AlF3

Transition metal hydrides play important roles in organometallic catalysis and synthetic reactions. Metallocenes niobium or tantalum hydride derivatives show high reactivities with variety of main group 13 Lewis acids. In this work, the nature of MH···B/Al interaction between Cp2M(L)H(M = V, Nb, and Ta) and BF3/AlF3 in 1:1 Lewis acid–base adducts as well as the influences of different types of ligands on the interactions is investigated. The results show that in Cp2M(L)H···BF3/AlF3, the MH···B interaction belongs to covalent interaction, and MH···Al shows partly covalent character. The covalent character of MH···B/Al bonds decreases with the increasing period of metal atom. The strength of MH···B/Al interaction is related to the type of metal atom (M) and ligand (L) in Cp2M(L)H, and the influences of L are larger than those of M. For the same M, the strength of MH···B/Al bonds is mainly influenced by the type of ligand, and they increase in the sequence of L = CO, C2H4, and P(CH3)3. The formation of Cp2M(L)H···BF3/AlF3 increases the polarity of M–H bond of Cp2M(L)H.

The Role Of Endothelial And Macrophage Scavenger Receptor Stabilin 1 And 2 In Early Atherosclerosis Development In Zebrafish

Atherosclerosis, the main underlying cause of cardiovascular disease and related morbidities, is a multifactorial disease in which liver endothelial cells and macrophages have shown to play an important role. Recently, it has been demonstrated that oxidized phospholipids in oxidized LDL (oxLDL) are pro-inflammatory and pro-atherogenic in hypercholesterolaemic mice. Multiple scavenger receptors are known for oxLDL. They form a superfamily of membrane bound receptors that bind and internalize different types of ligands including other modified lipoproteins, endogenous proteins and pathogens. Several studies, including a microarray study of our research group, have already identified scavenger receptors stabilin-1 and -2 (STAB1 and STAB2) as a risk factor for atherosclerosis, and therefore as potential targets for treatment. An upcoming and powerful model organism to study early atherogenesis and that allows non-invasive cell tracking studies is the zebrafish. Recent studies have demonstrated the possibility to induce (early) atherosclerosis in zebrafish. We have used Crispr/Cas9 mutagenesis to generate zebrafish stab1 and stab2 mutants. Our results show that oxLDL clearance by zebrafish scavenger endothelial cells (homologous to liver sinusoidal endothelial cells) is diminished in stab2 zebrafish mutants and is absent in stab1/2 double mutants. In stabilin mutants, macrophage oxLDL uptake is increased, suggesting a protective role for stabilins in foam cell formation. To study this further, we are currently performing an atherosclerosis study to examine foam cell formation and vascular lipid accumulation in stabilin mutant zebrafish.

Effective treatment of cancer metastasis using a dual-ligand nanoparticle.

Metastasis is responsible for the majority of deaths of breast cancer patients. While cytotoxic drugs are available with high potency to kill breast cancer cells, they are not designed to specifically seek and navigate in the dynamic and continuously changing microenvironment of metastatic disease. To effectively delivery chemotherapeutic agents to metastasis, we designed a dual-ligand nanoparticle loaded with doxorubicin by using two different types of ligands targeting EGFR and αvβ3 integrin. Metastatic cancer cells continuously change resulting in heterogeneity even across adjacent micrometastatic regions with variable expression of these targetable receptors. Using a mouse model of breast cancer metastasis, in vivo and ex vivo imaging showed that both EGFR and αvβ3 integrin-targeting were required to reliably direct the nanoparticle to metastasis and capture the spread and exact topology of the disease. Survival studies compared the anticancer efficacy of the standard drug, EGFR-targeting nanoparticle, αvβ3 integrin-targeting nanoparticle and the dual-ligand nanoparticle. While all the other treatments produced moderate therapeutic outcomes, treatment with the dual-ligand nanoparticle yielded significant improvement and event-free survival in a mouse model of breast cancer metastasis.

Combined Ensemble Docking and Machine Learning in Identification of Therapeutic Agents with Potential Inhibitory Effect on Human CES1.

The human carboxylesterase 1 (CES1), responsible for the biotransformation of many diverse therapeutic agents, may contribute to the occurrence of adverse drug reactions and therapeutic failure through drug interactions. The present study is designed to address the issue of potential drug interactions resulting from the inhibition of CES1. Based on an ensemble of 10 crystal structures complexed with different ligands and a set of 294 known CES1 ligands, we used docking (Autodock Vina) and machine learning methodologies (LDA, QDA and multilayer perceptron), considering the different energy terms from the scoring function to assess the best combination to enable the identification of CES1 inhibitors. The protocol was then applied on a library of 1114 FDA-approved drugs and eight drugs were selected for in vitro CES1 inhibition. An inhibition effect was observed for diltiazem (IC50 = 13.9 µM). Three others drugs (benztropine, iloprost and treprostinil), exhibited a weak CES1 inhibitory effects with IC50 values of 298.2 µM, 366.8 µM and 391.6 µM respectively. In conclusion, the binding site of CES1 is relatively flexible and can adapt its conformation to different types of ligands. Combining ensemble docking and machine learning approaches improves the prediction of CES1 inhibitors compared to a docking study using only one crystal structure.

NKp44-NKp44 Ligand Interactions in the Regulation of Natural Killer Cells and Other Innate Lymphoid Cells in Humans.

Natural Killer (NK) cells are potent cytotoxic cells belonging to the family of Innate Lymphoid Cells (ILCs). Their most characterized effector functions are directed to the control of aberrant cells in the body, including both transformed and virus-infected cells. NK cell-mediated recognition of abnormal cells primarily occurs through receptor-ligand interactions, involving an array of inhibitory and activating NK receptors and different types of ligands expressed on target cells. While most of the receptors have become known over many years, their respective ligands were only defined later and their impressive complexity has only recently become evident. NKp44, a member of Natural Cytotoxicity Receptors (NCRs), is an activating receptor playing a crucial role in most functions exerted by activated NK cells and also by other NKp44+ immune cells. The large and heterogeneous panel of NKp44 ligands (NKp44L) now includes surface expressed glycoproteins and proteoglycans, nuclear proteins that can be exposed outside the cell, and molecules that can be either released in the extracellular space or carried in extracellular vesicles. Recent findings have extended our knowledge on the nature of NKp44L to soluble plasma glycoproteins, such as secreted growth factors or extracellular matrix (ECM)-derived glycoproteins. NKp44L are induced upon tumor transformation or viral infection but may also be expressed in normal cells and tissues. In addition, NKp44-NKp44L interactions are involved in the crosstalk between NK cells and different innate and adaptive immune cell types. NKp44 expression in different ILCs located in tissues further extends the potential role of NKp44-NKp44L interactions.

Catalyst-Inspired Charge Carriers for High Energy Density Redox Flow Batteries

We introduce a theoretical design approach aiming at improving energy density of redox flow batteries (RFBs) via the utilization of redox noninnocent ligands capable of stabilizing a metal center in a wide range of oxidation states. Our findings suggest that this promotes the possibility of multiple redox events as well as high open circuit voltages. Specifically, we have proposed two Fe-coordination complexes (I, Fe(Me2Pytacn)(C2N3H2), and II, Fe(H2pmen)(C2N3H2)) combining two different types of ligands, i.e., catalyst-inspired scaffolds and triazole ring, which were previously shown to promote high and low oxidation states in transition metals, respectively. These complexes exhibit as many as six theoretical redox events in the full range of charge states +4 → –2, several of which reside within the electrochemical window of acetonitrile. Electronic structure calculations show that the Fe center exhibits oxidation states ranging from the very rare Fe4+ to Fe1+. Values of the reduction potentials as well as nature of the redox events of both complexes is found to be similar in their high +4 → +1 charge states. In contrast, while exhibiting qualitatively similar redox behavior in the lower 0 → –2 range, some differences in the electronic ground states, delocalization patterns as well as reduction potential values are also observed. The calculated open circuit voltages can reach values of 5.09 and 6.14 V for complexes I and II, respectively, and hold promise to be experimentally accessible within the electrochemical window of acetonitrile expanded by addition of ionic liquids. The current results obtained for these two complexes are intended to illustrate a more general principle based on the simultaneous utilization of two types of ligands responsible for the stabilization of high and low oxidation states of the metal that can be used to design the next-generation charge carriers capable of supporting multi-electron redox and operating in a broad range of charge states, leading to RFBs with greater energy density.

G Protein-coupled Receptors: One of the Most Important Drug Discovery Targets

G protein-coupled receptors are considered the most widely investigated drug discovery targets. They are the largest family of receptors with almost 800 genes in humans. Different types of ligands can activate these receptors, such as catecholamines, nucleotides, lipids, and gut microbiota, where some ligands could be bitopic. Nevertheless, some receptors have internal ligands bound to them. Activated G protein-coupled receptors have complex signaling pathways that are involved in almost all bodily functions. Furthermore, they constitute a large percentage of Food and Drug Administration marketed drugs and global share of drugs, in addition to a great proportion of drugs currently in clinical trials targeting these receptors. The approved G protein-coupled receptors targeted drugs and potential drugs are involved in the management of many diseases including cancer, inflammatory diseases, diabetes mellitus, hypertension, obesity, pain, and diseases of the central nervous system. Only 10% of G protein-coupled receptors are targeted. Different pharmacological approaches have been considered in drug discovery of these receptors including polypharmacology, allosteric modulators, biased agonism, tethered agonism, and pharmacogenomics. Advances in the technologies are promising to help in the discovery of new targets. The review's aim is to discuss the importance of G protein-coupled receptors as drug discovery targets.

Decoupled molecules with binding polynomials of bidegree (n,\xa02)

We present a result on the number of decoupled molecules for systems binding two different types of ligands. In the case of n and 2 binding sites respectively, we show that there are 2(n!)^{2} decoupled molecules to a generic binding polynomial. For molecules with more binding sites for the second ligand, we provide computational results.

High-sensitivity broadband colloidal quantum dot heterojunction photodetector for night-sky radiation

Being with excellent photosensibility, bandgap tunability and solution processibility, lead sulfide (PbS) colloidal quantum dot (CQD) gets one of the most attracting nanomaterials for photodetectors and light-harvesting devices. Usually short ligands are used to passivate the surface of CQDs to enhance the carrier mobility in QD films, and different types of ligands show distinct influence on the physical/electrical properties on the passivated CQD films. In this paper, a high-sensitivity broadband photodetector based on PbS-EDT/PbS-TBAl heterojunction by band-alignment engineering was presented. After optimizing the thickness of PbS CQD films, we found that the maximum specific detectivity of the photodiode ITO/ZnO(40 nm)/PbS-TBAl(160 nm)/PbS-EDT(40 nm)/Au reached to 3.93 × 1013 Jones and 5.52 × 1013 Jones under 2.0 μW/cm2 910 nm and 1.9 μW/cm2 500 nm illuminations, respectively, showing excellent stability in air and high sensitivity to weak signal (i.e. night-sky radiation). Further, the device performance of photodiode ITO/ZnO/PbS-TBAl/PbS-EDT/Au is compared with that of the control device ITO/ZnO/PbS-TBAI/Au, and the underneath mechanism for the enhanced performance is discussed.

20 Years Anniversary for SORLA/SORL1 (1996-2016)

SORLA is a sorting receptor known to control the intracellular trafficking of the amyloid precursor protein, which impaired pathway has a central role in the development of Alzheimer’s disease (AD). Recently, genetic analyses confirmed the casual role for SORLA in AD, as coding variants and single nucleotide polymorphisms of SORL1 (gene encoding SORLA) were identified in individuals affected by early-onset AD and late-onset AD, respectively. However, many other different types of ligands were found to target the receptor, thus strongly indicating that SORLA can exert multifunctional activities. In the current review, we provide an overview of the multi-ligand properties of SORLA, showing how this complex receptor is involved in a variety of biological functions.

Nanodisc-Targeted STD NMR Spectroscopy Reveals Atomic Details of Ligand Binding to Lipid Environments.

Saturation transfer difference (STD) NMR spectroscopy is one of the most popular ligand-based NMR techniques for the study of protein-ligand interactions. This is due to its robustness and the fact that it is focused on the signals of the ligand, without any need for NMR information on the macromolecular target. This technique is most commonly applied to systems involving different types of ligands (e.g., small organic molecules, carbohydrates or lipids) and a protein as the target, in which the latter is selectively saturated. However, only a few examples have been reported where membrane mimetics are the macromolecular binding partners. Here, we have employed STD NMR spectroscopy to investigate the interactions of the neurotransmitter dopamine with mimetics of lipid bilayers, such as nanodiscs, by saturation of the latter. In particular, the interactions between dopamine and model lipid nanodiscs formed either from charged or zwitterionic lipids have been resolved at the atomic level. The results, in agreement with previous isothermal titration calorimetry studies, show that dopamine preferentially binds to negatively charged model membranes, but also provide detailed atomic insights into the mode of interaction of dopamine with membrane mimetics. Our findings provide relevant structural information for the design of lipid-based drug carriers of dopamine and its structural analogues and are of general applicability to other systems.

FUNGSI DAN PEMERIKSAAN LIMFOSIT γδT (Functions and Examination of γδT lymphocytes)

T lymphocytes most have TCR α and β chains. However, TCR formed from γ and δ chains determine a new subset of T lymphocytes. γδTCR specific to different types of ligands, including bacterial phosphoantigen, nonclassical MHC-I molecules and unprocessed protein. γδT lymphocytes have several innate cell-like features that allow their early activation following the recognition of conserved stress-inducedligands. γδ T lymphocytes able to rapidly produce cytokines that regulate pathogen clearance, inflammation and tissue homeostasisin response to tissue stress. They are capable of generating more unique antigen receptors than γδ T lymphocytes and B lymphocytescombined, yet their repertoire of antigen receptors is dominated by specific subsets that recognize a limited number of antigens. A varietyof sometimes conflicting effectors functions have been ascribed to them, yet their biological functions remain unclear. Innate featuresof γδ T lymphocytes underlie their non-redundant role in several physiopathological contexts and are therefore being exploited in thedesign of new immunotherapeutic approaches. The purpose of writing is giving an overview in mainly functions of γδ T lymphocytes inthe immune system and laboratory tests that expand knowledge about the introduction of γδ T lymphocytes.

Characterization of two odorant binding proteins in Spodoptera exigua reveals functional conservation and difference

As the first biochemical step of olfactory reception and recognition, odorant binding proteins (OBPs) have been demonstrated to be essential. Considering functional diversities of OBPs within a single species, we here extended the characterization of two other OBPs from Spodoptera exigua, belonging to insect Classic OBPs. With a combination of transcriptome and Rapid Amplification of cDNA End (RACE) approaches, two OBP genes in S. exigua were identified, namely SexiOBP1 and OBP7. Expression pattern analysis revealed that both of them exhibited a distinct expression pattern, where OBP1 was broadly and highly expressed in several tissues including antennae of adults whereas OBP7 was abundant only in the antennae of both sexes, strongly indicative of olfactory roles. Further, binding assays showed that the two SexiOBPs shared a common odorant-response spectrum with considerable affinities to host odorants of acetophenone, farnesol and β-ionone (Ki<20μM). Specially, OBP1 could strongly bind an insect attractant β-caryophyllene (Ki=2.76μM) released by maize. Intriguingly, the major sex pheromone of S. exigua, Z9,E12-14:Ac, was the best ligand for OBP7 with Ki value of 7.58μM. Ligand structural analysis revealed that the two SexiOBPs were capable of accommodating different types of ligands in shape and size, possibly implying the plasticity of binding pockets. Ultimately, comparison of binding properties among 10 SexiOBPs including the two OBPs in this study implied a cross-talk in functions, i.e. different OBPs are also suitable to accept some common odorants except for unique ligands. Taken together, this study has provided evidence for their involvements in seeking and orientation of host plants, and meanwhile indicates functional conservation and differences between OBP1 and OBP7 from S. xigua.

Different ligand based monodispersed Pt nanoparticles decorated with rGO as highly active and reusable catalysts for the methanol oxidation

Addressed herein, a highly effective and monodisperse Pt/L@rGO nanocatalysts were successfully synthesized by using different types of ligands (pentylamine, Pt/PA@rGO and tripentylamine, Pt/TPA@rGO) and the impact of ligand on catalytic activity of the prepared nanomaterials have been examined for methanol oxidation. An easy and facile ultrasonication method was applied to produce highly efficient, monodispersed and durable (Pt) NPs dispersed on reduced graphene oxides (rGO). The structure morphology, composition and properties of Pt/L@rGO NPs were characterized by using different techniques such as ICP-OES, XPS, TEM, HRTEM, and XRD methods. A different ligand based monodisperse Pt (0) nanocatalysts have been compared with each other and commercial catalysts in terms of catalytic performance, life-time and reusability of catalyst for methanol oxidation reaction in THF at room temperature. All experimental results demonstrate the highly stable and reusable rGO furnished Pt (0) nanomaterials and their excellent catalytic performance in the methanol oxidation reactions at room temperature.

Trap-Induced Dispersive Transport and Dielectric Loss in PbS Nanoparticle Films

Abstract In this work, we investigate the electrical and dielectric response of lead sulfide (PbS) nanoparticle (NP) films with impedance spectroscopy. In particular, the influence of the ligand passivation on the surface trap state density of PbS NPs is demonstrated by comparing two different types of ligands: ethane-1,2-dithiol (EDT) and 3-sulfanylpropanoic acid (MPA). We observe that the MPA treatment passivates the PbS surface more efficiently than EDT. By analyzing the dielectric loss spectra, we are able to visualize shallow trap states in the bulk of PbS-EDT films and correlate this with the dispersive response observed in the impedance spectra. Evidence of deep trap states is revealed for both PbS-EDT and PbS-MPA diodes. Under illumination, the PbS-MPA and PbS-EDT films demonstrate almost identical trap profiles, showing solely the deep trap state densities. We conclude that the deep traps are related to the stoichiometry of the PbS NPs.

Inflammation and Notch signaling: a crosstalk with opposite effects on tumorigenesis

The Notch cascade is a fundamental and highly conserved pathway able to control cell-fate. The Notch pathway arises from the interaction of one of the Notch receptors (Notch1–4) with different types of ligands; in particular, the Notch pathway can be activated canonically (through the ligands Jagged1, Jagged2, DLL1, DLL3 or DLL4) or non-canonically (through various molecules shared by other pathways). In the context of tumor biology, the deregulation of Notch signaling is found to be crucial, but it is still not clear if the activation of this pathway exerts a tumor-promoting or a tumor suppressing function in different cancer settings. Untill now, it is well known that the inflammatory compartment is critically involved in tumor progression; however, inflammation, which occurs as a physiological response to damage, can also drive protective processes toward carcinogenesis. Therefore, the role of inflammation in cancer is still controversial and needs to be further clarified. Interestingly, recent literature reports that some of the signaling molecules modulated by the cells of the immune system also belong to or interact with the canonical and non-canonical Notch pathways, delineating a possible link between Notch activation and inflammatory environment. In this review we analyze the hypothesis that specific inflammatory conditions can control the activation of the Notch pathway in terms of biological effect, partially explaining the dichotomy of both phenomena. For this purpose, we detail the molecular links reported in the literature connecting inflammation and Notch signaling in different types of tumor, with a particular focus on colorectal carcinogenesis, which represents a perfect example of context-dependent interaction between malignant transformation and immune response.

On the performance of ruthenium dyes in dye sensitized solar cells: a free cluster approach based on theoretical indexes.

The performance of ruthenium dye sensitized solar cells (DSSC) with different types of ligand was studied by means of a theoretical model where the ruthenium complex is bound to two [Ti(OH)3](+) units, instead of the more usual cluster TiO2 model. Electron injection is proposed to proceed from a thermalized (3)MLCT state rather than from higher vibrational excited states. The efficiency of the dye linked to the two [Ti(OH)3](+) units was determined in terms of a global index (ξ), calculated as the product of three theoretical indexes (FI) built from the results of time-dependent density functional theory (TDDFT) calculations. The index considers the harvested and delivered energy (F1), the charge transferred to the semiconductor (F2), and dye regeneration (F3). The results show that this set of parameters is unique for each dye, and allows the comparative evaluation of the performance of a series of dyes, with a different ancillary ligand at each stage of the cell operation. The method provides insights that can help explain the improved performance of N3 and black dyes compared to other dyes.