Cis Ligands Research Articles

Understanding the Glycosylation Pathways Involved in the Biosynthesis of the Sulfated Glycan Ligands for Siglecs.

Carbohydrate sulfation plays a pivotal role in modulating the strength of Siglec-glycan interactions. Recently, new aspects of Siglec binding to sulfated cell surface carbohydrates have been discovered, but the class of glycan presenting these sulfated Siglec ligands has not been fully elucidated. In this study, the contribution of different classes of glycans to cis and trans Siglec ligands was investigated within cells expressing the carbohydrate sulfotransferase 1 (CHST1) or CHST2. For some Siglecs, the glycan class mediating binding was clear, such as O-glycans for Siglec-7 and N-glycans for Siglec-2 and Siglec-9. Both N-glycans and mucin-type O-glycans contributed to ligands for Siglec-3, -5, -8, and -15. However, significant levels of Siglec-3 and -8 ligands remained in CHST1-expressing cells lacking complex N-glycans and mucin-type O-glycans. A combination of genetic, pharmacological, and enzymatic treatment strategies ruled out heparan sulfates and glycoRNA as contributors, although Siglec-8 did exhibit some binding to glycolipids. Genetic disruption of O-mannose glycans within CHST1-expressing cells had a small but significant impact on Siglec-3 and -8 binding, demonstrating that this class of glycans can present sulfated Siglec ligands. We also investigated the ability of sulfated cis ligands to mask Siglec-3 and Siglec-7. For Siglec-7, cis ligands were again found to be mucin-type O-glycans. While N-glycans were the major sulfated trans ligands for Siglec-3, disruption of complex mucin-type O-glycans had the largest impact on Siglec-3 masking. Overall, this study enhances our knowledge of the types of sulfated glycans that can serve as Siglec ligands.

Catalysis activity and chemoselectivity control with the trans ligand in Ru-H pincer complexes.

(PhPNHP)Ru(H)(Cl)(CO) serves as a precatalyst to a variety of important catalytic transformations but most improvements have been restricted to the replacement of the CO ligand cis to the hydride or changing the Ph groups of the pincer for other aryl or alkyl groups. The ligand trans to the hydride is often another hydride and studies that utilize other trans ligands in catalysis are limited. In this work, we synthesized a series of [(PhPNHP)Ru(H)(CO)(L)][BPh4] complexes bearing isonitrile, PMe3, or a N-heterocyclic ligand trans to the Ru-H. We compared the new complexes abilities to catalyze the transfer hydrogenation of ketones. We found that all the trans ligands improved the chemoselectivity and stability of the catalysts; and strong π-accepting ligands resulted in poor catalytic activities whereas strong σ-donating ligands accelerated the catalysis.

Structural Diversity and Dimensionality of Three Cu(II)-dpds-C5O5 2- Coordination Polymers Controlled by the Coordination Sphere of Cu(II) Centers and the Coordination Modes of C5O5 2- (dpds = 4,4'-Dipyridyldisulfide).

Three supramolecular architectures, [Cu2(dpds)2(C5O5)2(H2O)4]·3H2O (1), [Cu(dpds)(C5O5)]·3H2O (2), and [Cu2(dpds)2(C5O5)2]·9H2O·C2H5OH (3) (dpds = 4,4'-dipyridyldisulfide and C5O5 2- (croconate) = dianion of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione), have been synthesized and structurally characterized. Compound 1 contains two crystallographically independent Cu(II) ions, which are both distorted octahedral geometry with elongation along the croconate- and H2O-bound axial positions and bonded with two N atoms of two dpds, two O atoms of one C5O5 2-, and two H2O molecules. Two crystallographically independent dpds ligands, both adopting the bis-monodentate bridging mode, connect two Cu(II) ions to form a one-dimensional zigzag chain-like coordination polymer. In 2 and 3, there are two and three crystallographically independent Cu(II) ions, respectively, which are all distorted octahedral geometries with elongation along the croconate-bound axial positions six-coordinated and bonded with two N atoms of two dpds ligands in cis- or/and trans-forms and four O atoms of two C5O5 2- ligands. The dpds ligands in 2 and 3 all adopt the bis-monodentate bridging mode, and the C5O5 2- ligands act as bridging ligands with bridging bis-bidentate through three C5O5 2- oxygen atoms in 2 and bridging bis-bidentate through four adjacent C5O5 2- oxygen atoms in 3, respectively, linking the Cu(II) ions to generate a two-dimensional layered and a three-dimensional metal-organic framework, respectively. The structural diversity and dimensionality observed in 1-3 may be attributed to the cis- or/and trans-coordination sphere of Cu(II) centers with two dpds ligands and the coordination modes of croconate ligands. Thermal stability and in situ temperature-dependent structural variations of 1-3 have been verified by thermogravimetric analysis and powder X-ray diffraction measurements. Compounds 1 and 3 both exhibit water vapor capture behaviors with hysteresis isotherms.

Dissecting the Ability of Siglecs To Antagonize Fcγ Receptors.

Fcγ receptors (FcγRs) play key roles in the effector function of IgG, but their inappropriate activation plays a role in several disease etiologies. Therefore, it is critical to better understand how FcγRs are regulated. Numerous studies suggest that sialic acid-binding immunoglobulin-type lectins (Siglecs), a family of immunomodulatory receptors, modulate FcγR activity; however, it is unclear of the circumstances in which Siglecs can antagonize FcγRs and which Siglecs have this ability. Using liposomes displaying selective ligands to coengage FcγRs with a specific Siglec, we explore the ability of Siglec-3, Siglec-5, Siglec-7, and Siglec-9 to antagonize signaling downstream of FcγRs. We demonstrate that Siglec-3 and Siglec-9 can fully inhibit FcγR activation in U937 cells when coengaged with FcγRs. Cells expressing Siglec mutants reveal differential roles for the immunomodulatory tyrosine-based inhibitory motif (ITIM) and immunomodulatory tyrosine-based switch motif (ITSM) in this inhibition. Imaging flow cytometry enabled visualization of SHP-1 recruitment to Siglec-3 in an ITIM-dependent manner, while SHP-2 recruitment is more ITSM-dependent. Conversely, both cytosolic motifs of Siglec-9 contribute to SHP-1/2 recruitment. Siglec-7 poorly antagonizes FcγR activation for two reasons: masking by cis ligands and differences in its ITIM and ITSM. A chimera of the Siglec-3 extracellular domains and Siglec-5 cytosolic tail strongly inhibits FcγR when coengaged, providing evidence that Siglec-5 is more like Siglec-3 and Siglec-9 in its ability to antagonize FcγRs. Additionally, Siglec-3 and Siglec-9 inhibited FcγRs when coengaged by cells displaying ligands for both the Siglec and FcγRs. These results suggest a role for Siglecs in mediating FcγR inhibition in the context of an immunological synapse, which has important relevance to the effectiveness of immunotherapies.

CD47 masks pro-phagocytic ligands in cis on tumor cells to suppress antitumor immunity.

Cancer cells often overexpress CD47, which triggers the inhibitory receptor SIRPα expressed on macrophages, to elude phagocytosis and antitumor immunity. Pharmacological blockade of CD47 or SIRPα is showing promise as anticancer therapy, although CD47 blockade has been associated with hematological toxicities that may reflect its broad expression pattern on normal cells. Here we found that, in addition to triggering SIRPα, CD47 suppressed phagocytosis by a SIRPα-independent mechanism. This mechanism prevented phagocytosis initiated by the pro-phagocytic ligand, SLAMF7, on tumor cells, due to a cis interaction between CD47 and SLAMF7. The CD47-SLAMF7 interaction was disrupted by CD47 blockade and by a first-in-class agonist SLAMF7 antibody, but not by SIRPα blockade, thereby promoting antitumor immunity. Hence, CD47 suppresses phagocytosis not only by engaging SIRPα, but also by masking cell-intrinsic pro-phagocytic ligands on tumor cells and knowledge of this mechanism may influence the decision between CD47 blockade or SIRPα blockade for therapeutic purposes.

Interactions between Siglec-8 and endogenous sialylated cis ligands restrain cell death induction in human eosinophils and mast cells.

Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a sialoside-binding receptor expressed by eosinophils and mast cells that exhibits priming status- and cell type-dependent inhibitory activity. On eosinophils that have been primed with IL-5, GM-CSF, or IL-33, antibody ligation of Siglec-8 induces cell death through a pathway involving the β2 integrin-dependent generation of reactive oxygen species (ROS) via NADPH oxidase. In contrast, Siglec-8 engagement on mast cells inhibits cellular activation and mediator release but reportedly does not impact cell viability. The differences in responses between cytokine-primed and unprimed eosinophils, and between eosinophils and mast cells, to Siglec-8 ligation are not understood. We previously found that Siglec-8 binds to sialylated ligands present on the surface of the same cell (so-called cis ligands), preventing Siglec-8 ligand binding in trans. However, the functional relevance of these cis ligands has not been elucidated. We therefore explored the potential influence of cis ligands of Siglec-8 on both eosinophils and mast cells. De-sialylation using exogenous sialidase profoundly altered the consequences of Siglec-8 antibody engagement on both cell types, eliminating the need for cytokine priming of eosinophils to facilitate cell death and enabling Siglec-8-dependent mast cell death without impacting anti-Siglec-8 antibody binding. The cell death process licensed by de-sialylation resembled that characterized in IL-5-primed eosinophils, including CD11b upregulation, ROS production, and the activities of Syk, PI3K, and PLC. These results implicate cis ligands in restraining Siglec-8 function on eosinophils and mast cells and reveal a promising approach to the selective depletion of mast cells in patients with mast cell-mediated diseases.

A photoaffinity glycan-labeling approach to investigate immunoglobulin glycan-binding partners.

Glycans play a pivotal role in biology. However, because of the low-affinity of glycan-protein interactions, many interaction pairs remain unknown. Two important glycoproteins involved in B-cell biology are the B-cell receptor and its secreted counterpart, antibodies. It has been indicated that glycans expressed by these B-cell-specific molecules can modulate immune activation via glycan-binding proteins. In several autoimmune diseases, an increased prevalence of variable domain glycosylation of IgG autoantibodies has been observed. Especially, the hallmarking autoantibodies in rheumatoid arthritis, anti-citrullinated protein antibodies, carry a substantial amount of variable domain glycans. The variable domain glycans expressed by these autoantibodies are N-linked, complex-type, and α2-6 sialylated, and B-cell receptors carrying variable domain glycans have been hypothesized to promote selection of autoreactive B cells via interactions with glycan-binding proteins. Here, we use the anti-citrullinated protein antibody response as a prototype to study potential in solution and in situ B-cell receptor-variable domain glycan interactors. We employed SiaDAz, a UV-activatable sialic acid analog carrying a diazirine moiety that can form covalent bonds with proximal glycan-binding proteins. We show, using oligosaccharide engineering, that SiaDAz can be readily incorporated into variable domain glycans of both antibodies and B-cell receptors. Our data show that antibody variable domain glycans are able to interact with inhibitory receptor, CD22. Interestingly, although we did not detect this interaction on the cell surface, we captured CD79 β glycan-B-cell receptor interactions. These results show the utility of combining photoaffinity labeling and oligosaccharide engineering for identifying antibody and B-cell receptor interactions and indicate that variable domain glycans appear not to be lectin cis ligands in our tested conditions.

Reactivity of four coordinate iridium complex towards hydrogen: An experimental and computational study

Reaction of a four coordinate, 16-electron Ir complex, [Ir(iPr)4(POCOP)(PPh3)] (4) ((iPr)4(POCOP = 2,6-bis(di-isopropyl phosphinito)benzene, κ3-C6H3-1,3-[OP(iPr)2]2), with H2 resulted in an oxidative addition product, cis-dihydride complex, cis-[Ir(H)2(iPr)4(POCOP)(PPh3)] (cis-5) presumably via the intermediacy of a sigma complex, [Ir(η2-H2)(iPr)4(POCOP)(PPh3)]. The cis-dihydride complex completely isomerizes to the trans-dihydride complex trans-[Ir(H)2(iPr)4(POCOP)(PPh3)] (trans-5) under ambient conditions in about 3 h. It was found that the steric and electronic features on the iridium center have significant influence on the approach of H2 onto the metal center followed by oxidative addition and isomerization. The isomerization process was studied in detail and all the mechanistic aspects have been elucidated using a combination of both experimental work and computation. The cis-dihydride complex isomerizes to the trans-dihydride by compensating the trans influence of the strongly trans-directing hydride ligand. A mechanism involving the exchange of the position of PPh3 with a hydride ligand cis to itself via PPh3 dissociation and re-coordination thereby resulting in the formation of the trans-dihydride complex, has been proposed for the isomerization. The cis-dihydride was found to be a highly active catalyst for hydrogenation of ethylene. A competing reactivity study of cis-dihydride between isomerization versus insertion of C2H4 into the Ir—H bond, was studied experimentally and computationally.

A Ruthenium(II) Nitrosyl Complex of N-Dehydroacetic Acid-Sulfadiazine: Synthesis, DFT Studies and in silico ADME Properties

A sulpha drug-derived Schiff base ligand N-dehydroacetic acid-sulfadiazine was synthesized by treatment of dehydroacetic acid and sulfadiazine. A mononuclear Ru(II) nitrosyl complex of the Schiff base ligand cis-[RuCl2(NO)(PPh3)(dha-sdz)] was synthesized. The complex was characterized by spectral (IR, 1H NMR and UV/visible) techniques and physico-chemical studies. A cyclic voltammetric technique observed the electrochemistry of the complex compound. Therefore, the Gaussian 09 programme has been used to optimized molecular structure, electronic surface analysis, NLO properties through DFT approaches via mixed basis set at B3LYP/LANL2DZ level of theory. The 1H NMR spectrum of complex compound was computed with the GIAO method and correlated to experimental chemical shift. The TD-DFT based electronic absorption spectrum was computed using the PCM model. Additionally, the synthesized compound was predicting its in silico ADME properties, showing good physico-chemical and bioactivity. Finally, the in vitro antioxidant activity of the studied compound was monitored via two radical scavenging inhibitors.

The conserved C2 phospholipid-binding domain in Delta contributes to robust Notch signalling

Accurate Notch signalling is critical for development and homeostasis. Fine-tuning of Notch–ligand interactions has substantial impact on signalling outputs. Recent structural studies have identified a conserved N-terminal C2 domain in human Notch ligands which confers phospholipid binding in vitro. Here, we show that Drosophila ligands Delta and Serrate adopt the same C2 domain structure with analogous variations in the loop regions, including the so-called β1-2 loop that is involved in phospholipid binding. Mutations in the β1-2 loop of the Delta C2 domain retain Notch binding but have impaired ability to interact with phospholipids in vitro. To investigate its role in vivo, we deleted five residues within the β1-2 loop of endogenous Delta. Strikingly, this change compromises ligand function. The modified Delta enhances phenotypes produced by Delta loss-of-function alleles and suppresses that of Notch alleles. As the modified protein is present on the cell surface in normal amounts, these results argue that C2 domain phospholipid binding is necessary for robust signalling in vivo fine-tuning the balance of trans and cis ligand–receptor interactions.

Bis(N-picolinamido)cobalt(II) Complexes Display Antifungal Activity toward Candida albicans and Aspergillus fumigatus.

This report highlights the synthesis and characterization of ten new bis(N‐picolinamido)cobalt(II) complexes of the type [(L)2CoX2]0/2+, whereby L=N‐picolinamide ligand and X=diisothiocyanato (−NCS), dichlorido (−Cl) or diaqua (−OH2) ligands. Single crystal X‐ray (SC‐XRD) analysis for nine of the structures are reported and confirm the picolinamide ligand is bound to the Co(II) center through a neutral N,O binding mode. With the addition of powder X‐ray diffraction (PXRD), we have confirmed the cis and trans ligand arrangements of each complex. All complexes were screened against several fungal species and show increased antifungal activity. Notably, these complexes had significant activity against strains of Candida albicans and Aspergillus fumigatus, with several compounds exhibiting growth inhibition of >80 %, and onecompound inhibiting Aspergillus fumigatus hyphal growth by >90 %. Conversely, no antifungal activity was exhibited toward Cryptococcus neoformans and no cytotoxicity towards mammalian cell lines.

Shared Binding Mode of Perrottetinene and Tetrahydrocannabinol Diastereomers inside the CB1 Receptor May Incentivize Novel Medicinal Drug Design: Findings from an in Silico Assay.

In recent years, therapeutic compounds derived from phytocannabinoids have brought renewed attention to the benefits they offer to ameliorate chronic disease symptoms. Among cannabinoids, tetrahydrocannabinol (THC) is a well-known component of the Cannabis plant, whose active principles have been studied through the years. Another psychoactive phytocannabinoid, derived from liverworts Radula, perrottetinene (PET), has created interest, especially as a pharmaceutical product and for its legal recreational use. Unfortunately, so far, the interaction mode of these compounds at the type 1 cannabinoid receptors (CB1R) binding site remains unknown, and no experimental three-dimensional structure in complex with THC or PET is available in the Protein Data Bank. Today, many computational methodologies can assist in this crusade and help unveil how these molecules bind, based on the already known pose of a structurally similar compound. In this work, we aim to elucidate the binding mode of THC and PET molecules in both cis and trans conformers, using a combination of several computational methodologies, including molecular docking, molecular dynamics, free energy calculations, and protein-energy network studies. We found that THC and PET interact similarly with the CB1R, in a different conformation depending on the considered diastereomer. We have observed that cis ligands adopted a half-chair conformation of the cycle ring containing the dimethyl group, assuming an axial or equatorial conformation producing a different induced fitting of the surrounding residues compared with trans ligands, with higher interaction energy than the trans conformer. For PET, we have seen that Trp-279 and Trp-356 have a marked influence on the binding. After binding, Trp-279 accommodates its side chain to better interact with the PET's terminal phenyl group, disturbing CB1R residues communication. The interaction with Trp-356 might impair the activation of CB1R and can influence the binding of PET as a partial agonist. Understanding the PET association with CB1R from a molecular perspective can offer a glimpse of preventing potential toxicological or recreational effects since it is an attractive lead for drug development with fewer side effects than trans-THC.

195Pt and 15N NMR Data in Square Planar Platinum(II) Complexes of the Type [Pt(NH3)aXb]n (Xb = Combination of Halides): “NMR Effective Molecular Radius” of Coordinated Ammonia

By studying a model set of square‐planar [Pt(NH3)aXb]n (a + b = 4; Xb = combination of b halido ligands; n = 2 – b) complexes, we found that their δ(195Pt) NMR chemical shift decreases proportionally to the platinum bonded halido ligands' ionic radii overall sum. This confirms also for these systems, the already observed NMR shielding attributed to pseudo ring currents, circulating around the M–X bond axis. Moreover, the present data show that also the NH3 ligands are characterized by a constant NMR shielding ability toward the central metal. This could be rationalized in term of a “NMR effective molecular radius” of the NH3 ligand, affecting the observed δ(195Pt) as previously found for halido ligands. Interestingly, a δ(15N) decrease is observed in Pt bonded NH3 ligands if the ionic radius of a cis halido ligand is increased. The opposite occurs if the ionic radius of a trans halido ligand is increased. The two contrasting effects stem from both shielding electric ring currents affecting the cis ligands and prevailing trans‐influence due to coordinated halido ligands.

Crystal structures of a series of bis-(acetyl-aceto-nato)oxovanadium(IV) complexes containing N-donor pyridyl ligands.

Crystal structures for a series of bis-(acetyl-acetonato)oxovanadium(IV) complexes containing N-donor pyridyl ligands are reported, namely, bis-(acetyl-acetonato-κ2 O,O')oxido(pyridine-κN)vanadium(IV), [V(C5H7O2)2O(C5H5N)], 1, bis-(acetyl-acetonato-κ2 O,O')oxido(pyridine-4-carbo-nitrile-κN)vanadium(IV), [V(C5H7O2)2O(C6H4N2)], 2, and bis-(acetyl-acetonato-κ2 O,O')(4-meth-oxy-pyridine-κN)oxidovanadium(IV), [V(C5H7O2)2O(C6H7NO)], 3, Compounds 1-3 have the formulae VO(C5H7O2)2 L, where L = pyridine (1), 4-cyano-pyridine (2), and 4-meth-oxy-pyridine (3). Compound 1 was previously reported [Meicheng et al. (1984 ▸). Kexue Tongbao, 29, 759-764 and DaSilva, Spiazzi, Bortolotto & Burrow (2007). Acta Crystallogr., E63, m2422] and redetermined here at cryogenic temperatures. Compounds 1 and 2 as pyridine and 4-cyano-pyridine adducts, respectively, crystallize as distorted octa-hedral structures with the oxo and pyridyl ligands trans to one another. A crystallographic twofold axis runs through the O-V-N bonds. Compound 3 containing a 4-meth-oxy-pyridine ligand crystallizes as a distorted octa-hedral structure with the oxo and pyridyl ligands cis to one other, removing the twofold symmetry seen in the other complexes.

Evidence for Modulation of Oxygen Rebound Rate in Control of Outcome by Iron(II)- and 2-Oxoglutarate-Dependent Oxygenases.

Iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenases generate iron(IV)-oxo (ferryl) intermediates that can abstract hydrogen from aliphatic carbons (R-H). Hydroxylation proceeds by coupling of the resultant substrate radical (R•) and oxygen of the Fe(III)-OH complex ("oxygen rebound"). Nonhydroxylation outcomes result from different fates of the Fe(III)-OH/R• state; for example, halogenation results from R• coupling to a halogen ligand cis to the hydroxide. We previously suggested that halogenases control substrate-cofactor disposition to disfavor oxygen rebound and permit halogen coupling to prevail. Here, we explored the general implication that, when a ferryl intermediate can ambiguously target two substrate carbons for different outcomes, rebound to the site capable of the alternative outcome should be slower than to the adjacent, solely hydroxylated site. We evaluated this prediction for (i) the halogenase SyrB2, which exclusively hydroxylates C5 of norvaline appended to its carrier protein but can either chlorinate or hydroxylate C4 and (ii) two bifunctional enzymes that normally hydroxylate one carbon before coupling that oxygen to a second carbon (producing an oxacycle) but can, upon encountering deuterium at the first site, hydroxylate the second site instead. In all three cases, substrate hydroxylation incorporates a greater fraction of solvent-derived oxygen at the site that can also undergo the alternative outcome than at the other site, most likely reflecting an increased exchange of the initially O2-derived oxygen ligand in the longer-lived Fe(III)-OH/R• states. Suppression of rebound may thus be generally important for nonhydroxylation outcomes by these enzymes.

Isolation of a Square-Planar Th(III) Complex: Synthesis and Structure of [Th(OC6H2tBu2-2,6-Me-4)4]1.

Reduction of Th(OC6H2tBu2-2,6-Me-4)4 using either KC8 or Li in THF forms a new example of a crystallographically characterizable Th(III) complex in the salts [K(THF)5(Et2O)][Th(OC6H2tBu2-2,6-Me-4)4] and [Li(THF)4][Th(OC6H2tBu2-2,6-Me-4)4]. Surprisingly, in each structure the four aryloxide ligands are arranged in a square-planar geometry, the first example of this coordination mode for an f element complex. The Th(III) ion and four oxygen donor atoms are coplanar to within 0.05 Å with O-Th-O angles of 89.27(8) to 92.02(8)° between cis ligands. The ligands have Th-O-C(ipso) angles of 173.9(2) to 178.6(4)°, and the aryl rings make angles of 58.5 to 65.1° with the ThO4 plane. The effect of the eight tert-butyl substituents in generating the unusual structure through packing and/or dispersion forces is discussed. EPR spectroscopy reveals an axial signal consistent with a metal-based radical in a planar complex. DFT calculations yield a C4-symmetric structure that accommodates a low-lying SOMO of 6dz2 character with 7s Rydberg admixture.

Four isostructural lanthanide(III) coordination compounds based on a new N-oxydic pyridyl naphthalenediimide ligand: synthesis and characterization.

Naphthalenediimides, an attractive class of electron-deficient organic dyes with rich redox and photoredox properties, have been investigated extensively as building blocks for coordination networks or metal-organic frameworks in recent decades. However, most of the available work has focused on d-block metal cations rather than f-block lanthanide ions, whose complexes exhibit a large variability in coordination numbers. In this article, four coordination polymers composed of naphthalenediimides and lanthanide cations, namely catena-poly[[[tris(nitrato-κ2O,O')lanthanide]-bis{μ-N,N'-bis[(1-oxidopyridin-1-ium-3-yl)methyl]-1,8:4,5-naphthalenetetracarboxdiimide-κ2O:O'}-[tris(nitrato-κ2O,O')lanthanide]-μ-N,N'-bis[(1-oxidopyridin-1-ium-3-yl)methyl]-1,8:4,5-naphthalenetetracarboxdiimide-κ2O:O'] methanol disolvate], {[Ln(C26H16N4O4)1.5(NO3)3]·CH3OH}n, with Ln = Eu, 1, Gd, 2, Dy, 3, and Er, 4, have been successfully synthesized under hydrothermal conditions. Single-crystal X-ray diffraction analyses revealed that the four compounds are isomorphic and that each asymmetric unit contains one nine-coordinated Ln centre, one and a half diimide ligands, three nitrate anions and one uncoordinated methanol molecule. In addition, each metal centre is surrounded by nine O atoms in a distorted tricapped trigonal-prismatic geometry. Two centres are bridged by two cis ligands to form a ring, which is further bridged by trans ligands to generate one-dimensional chains. Neighbouring chains are stacked via π-π interactions between pyridine rings to give a two-dimensional structure, which is stabilized by π-π interactions between naphthalene rings, forming the final three-dimensional supermolecular network. Solid-state optical diffuse-reflectance spectral studies indicate that compound 4 is a potential wide band gap semiconductor.

N-cadherin provides a cis and trans ligand for astrotactin that functions in glial-guided neuronal migration

Prior studies demonstrate that astrotactin (ASTN1) provides a neuronal receptor for glial-guided CNS migration. Here we report that ASTN1 binds N-cadherin (CDH2) and that the ASTN1:CDH2 interaction supports cell-cell adhesion. To test the function of ASTN1:CDH2 binding in glial-guided neuronal migration, we generated a conditional loss of Cdh2 in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronal Cdh2, and more severe migration defects occurred after a conditional loss of glial Cdh2 Expression in granule cells of a mutant form of ASTN1 that does not bind CDH2 also slowed migration. Moreover, in vitro chimeras of granule cells and glia showed impaired neuron-glia attachment in the absence of glial, but not neuronal, Cdh2 Thus, cis and trans bindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron-glial bridge complex that promotes glial-guided neuronal migration.

Dicarbonyl cis-[M(CO)2(N,O)(C)(P)] (M = Re, 99mTc) Complexes with a New [2 + 1 + 1] Donor Atom Combination.

The synthesis and characterization of the dicarbonyl mixed ligand cis-[Re(CO)2(quin)(cisc)(PPh3)] complex, 4, where quin is the deprotonated quinaldic acid, cisc is cyclohexyl isocyanide, and PPh3 is triphenylphosphine, is presented. The synthesis of 4 proceeds in three steps. In the first, the intermediate fac-[Re(CO)3(quin)(H2O)] aqua complex 2 is generated from the fac-[NEt4]2[Re(CO)3Br3] precursor, together with the brominated products fac-[Re(CO)3(quinH)(Br)] 1a and fac-[NEt4][Re(CO)3(quin)(Br)] 1b, in low yield. In the following step, replacement of the aqua ligand of complex 2 by the monodentate isocyanide ligand leads to the formation of fac-[Re(CO)3(quin)(cisc)], 3. In the third step replacement of the species trans to the isocyanide carbonyl group of 3 by a phosphine generates complex 4. The Re complexes 2-4 were prepared in high yield and fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography. At the technetium-99m (99mTc) tracer level, the analogous complexes 3' and 4' were produced in high radiochemical purity, characterized by comparative reverse phase high-performance liquid chromatography and showed high resistance to transchelation by histidine or cysteine. This new [N,O][C][P] donor atom combination with the cis-[M(CO)2]+ core (M = Re, 99mTc) is a promising scaffold for the development of novel diagnostic and therapeutic targeted radiopharmaceuticals.

Unlocking Structural Diversity in Gold(III) Hydrides: Unexpected Interplay of cis/ trans-Influence on Stability, Insertion Chemistry, and NMR Chemical Shifts.

The synthesis of new families of stable or at least spectroscopically observable gold(III) hydride complexes is reported, including anionic cis-hydrido chloride, hydrido aryl, and cis-dihydride complexes. Reactions between (C^C)AuCl(PR3) and LiHBEt3 afford the first examples of gold(III) phosphino hydrides (C^C)AuH(PR3) (R = Me, Ph, p-tolyl; C^C = 4,4′-di-tert-butylbiphenyl-2,2′-diyl). The X-ray structure of (C^C)AuH(PMe3) was determined. LiHBEt3 reacts with (C^C)AuCl(py) to give [(C^C)Au(H)Cl]−, whereas (C^C)AuH(PR3) undergoes phosphine displacement, generating the dihydride [(C^C)AuH2]−. Monohydrido complexes hydroaurate dimethylacetylene dicarboxylate to give Z-vinyls. (C^N^C)Au pincer complexes give the first examples of gold(III) bridging hydrides. Stability, reactivity and bonding characteristics of Au(III)–H complexes crucially depend on the interplay between cis and trans-influence. Remarkably, these new gold(III) hydrides extend the range of observed NMR hydride shifts from δ −8.5 to +7 ppm. Relativistic DFT calculations show that the origin of this wide chemical shift variability as a function of the ligands depends on the different ordering and energy gap between “shielding” Au(dπ)-based orbitals and “deshielding” σ(Au–H)-type MOs, which are mixed to some extent upon inclusion of spin–orbit (SO) coupling. The resulting 1H hydride shifts correlate linearly with the DFT optimized Au–H distances and Au–H bond covalency. The effect of cis ligands follows a nearly inverse ordering to that of trans ligands. This study appears to be the first systematic delineation of cis ligand influence on M–H NMR shifts and provides the experimental evidence for the dramatic change of the 1H hydride shifts, including the sign change, upon mutual cis and trans ligand alternation.