Y-shaped Ligand Research Articles

Solvent-Induced In(III)-MOFs with Controllable Interpenetration Degree Performing High-Efficiency Separation of CO2/N2 and CO2/CH4.

Herein, three In(III)-based metal-organic frameworks (In-MOFs) with different degrees of interpenetration (DOI), namely In-MOF-1, In-MOF-2, and In-MOF-3, constructed by In3+ and Y-shaped ligands 4,4',4″-s-triazine-2,4,6-triyltribenzoate (H3TATB), are successfully synthesized through the ionothermal/solvothermal method. Subsequently, three novel In-MOFs, including noninterpenetration polycatenation, 2-fold interpenetrated, and 4-fold interpenetrated structure, are employed as the platform for systematically investigating the separation efficiency of CO2/N2, CO2/CH4, and CO2/CH4/N2 mixture gas system. Among them, In-MOF-2 shows the highest CO2 uptake capacities at 298 K and simultaneously possesses the low adsorption enthalpy of CO2 (26.4 kJ/mol at low coverage), a feature desirable for low-energy-cost adsorbent regeneration. The CO2/N2 (v: v = 15/85) selectivity of In-MOF-2 reaches 37.6 (at 298 K and 1 bar), also revealing outstanding selective separation ability from flue gases and purifying natural gas, affording a unique robust separation material as it has moderate DOI and pore size. In-MOF-2 shows exceptional stability and feasibility to achieve reproducibility. Aperture adjustment makes In-MOF-2 a versatile platform for selectively capturing CO2 from flue gases or purifying natural gas.

Hydrothermal Synthesis and Structural Characterization of a Novel Ni(II) Coordination Polymer Based on a Y-shaped Ligand

Hydrothermal Synthesis and Structural Characterization of a Novel Ni(II) Coordination Polymer Based on a Y-shaped Ligand

Structural insights into the interaction of three Y-shaped ligands with PI3Kα

Class IA phosphoinositide 3-kinase alpha (PI3Kα) is an important drug target because it is one of the most frequently mutated proteins in human cancers. However, small molecule inhibitors currently on the market or under development have safety concerns due to a lack of selectivity. Therefore, other chemical scaffolds or unique mechanisms of catalytic kinase inhibition are needed. Here, we report the cryo-electron microscopy structures of wild-type PI3Kα, the dimer of p110α and p85α, in complex with three Y-shaped ligands [cpd16 (compound 16), cpd17 (compound 17), and cpd18 (compound 18)] of different affinities and no inhibitory effect on the kinase activity. Unlike ATP-competitive inhibitors, cpd17 adopts a Y-shaped conformation with one arm inserted into a binding pocket formed by R770 and W780 and the other arm lodged in the ATP-binding pocket at an angle that is different from that of the ATP phosphate tail. Such a special interaction induces a conformation of PI3Kα resembling that of the unliganded protein. These observations were confirmed with two isomers (cpd16 and cpd18). Further analysis of these Y-shaped ligands revealed the structural basis of differential binding affinities caused by stereo- or regiochemical modifications. Our results may offer a different direction toward the design of therapeutic agents against PI3Kα.

Fructose and biotin co-modified liposomes for dual-targeting breast cancer

Chemotherapy, as the main treatment for breast cancer, inevitably damages normal tissues due to the lack of targeting. Various nano targeting drug delivery systems (TDDS) have the potential to be developed as anticancer therapeutics. Although mono-ligand-directed liposomes have been used with some success, dual-ligand-directed liposomes exhibit promising advantages. In current work, we synthesized a Y-shaped ligand covalently linking fructose and biotin (Fru-Bio-Chol) to prepare a dual-targeting liposome Fru-Bio-Lip for breast cancer. The targeting ability was evaluated by comparing the Fru-Bio-Lip with the non-modified liposome (Lip), fructose or biotin mono modified liposomes (Fru-Lip and Bio-Lip), and another dual-targeting liposome (Fru + Bio-Lip) physically mixing fructose and biotin mono modified ligands (Fru-Chol and Bio-Chol). The cellular uptake of Fru-Bio-Lip is 3.27-, 1.81-, 2.19-, 1.15-times that of Lip, Fru-Lip, Bio-Lip and Fru + Bio-Lip on 4T1 cells, and 3.11-, 1.80-, 1.89-, 1.15-times on MCF-7 cells. Additionally, the uptake mechanism indicates the uptake of Fru-Bio-Lip is energy-dependently achieved through multiple endocytosis pathway with a dual recognition of fructose and biotin by GLUT5 and SMVT. The cytotoxicity and apoptosis assay show PTX-Fru-Bio-Lip among liposomes have the strongest proliferation inhibitory effect on breast cancer cells, and the apoptosis rate is 1.7-times that of PTX-Lip. In vivo images indicate Fru-Bio-Lip have the strongest tumour enrichment ability, which is 2.76-, 1.60-, 1.96-, 1.40-times that of Lip, Fru-Lip, Bio-Lip and Fru + Bio-Lip, respectively. Overall, the fructose and biotin covalently modified liposomes improved breast cancer targeting ability, demonstrating great potential as a drug delivery system for breast cancer.

Molecular Scaffolds as Double-Targeting Agents For the Diagnosis and Treatment of Neuroblastoma.

The selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta-iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y-shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y-structure. The cellular uptake capacity of these double-targeting ligands has been evaluated in vitro and in vivo, yielding one specific Y-shaped structure that is able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent. This Y-shaped ligand can provide a powerful tool for the current treatment and diagnosis of this disease.

Crystal structures, thermodynamics and accelerating thermal decomposition of RDX: two new energetic coordination polymers based on a Y-shaped ligand of tris(5-aminotetrazole)triazine

Two new energetic coordination polymers were prepared under hydrothermal condition. They have good detonation velocity, detonation pressure and effective acceleration effect toward the thermal decomposition of RDX (1,3,5-trinitro-1,3,5-triazinane).

Molecular association model of PPARα and its new specific and efficient ligand, pemafibrate: Structural basis for SPPARMα

Peroxisome proliferator-activated receptor-α (PPARα) is a ligand-activated transcription factor involved in the regulation of lipid homeostasis and improves hypertriglyceridemia. Pemafibrate is a novel selective PPARα modulator (SPPARMα) that activates PPARα transcriptional activity. Here, we computationally constructed the structure of the human PPARα in a complex with pemafibrate, along with that of hPPARα complexed with the classical fenofibrate, and studied their interactions quantitatively by using the first-principles calculations-based fragment molecular orbital (FMO) method. Comprehensive structural and protein-ligand binding elucidation along with the in vitro luciferase analysis let us to identify pemafibrate as a novel SPPARMα. Unlike known fibrate ligands, which bind only with the arm I of the Y-shaped ligand binding pocket, the Y-shaped pemafibrate binds to the entire cavity region. This lock and key nature causes enhanced induced fit in pemafibrate-ligated PPARα. Importantly, this selective modulator allosterically changes PPARα conformation to form a brand-new interface, which in turn binds to PPARα co-activator, PGC-1α, resulting in the full activation of PPARα. The structural basis for the potent effects of pemafibrate on PPARα transcriptional activity predicted by the in silico FMO methods was confirmed by in vitro luciferase assay for mutants. The unique binding mode of pemafibrate reveals a new pattern of nuclear receptor ligand recognition and suggests a novel basis for ligand design, offering cues for improving the binding affinity and selectivity of ligand for better clinical consequences. The findings explain the high affinity and efficacy of pemafibrate, which is expected to be in the clinical use soon.

Spin-Canted Antiferromagnetic Ordering in Transition Metal–Organic Frameworks Based on Tetranuclear Clusters with Mixed V- and Y-Shaped Ligands

Four transition metal–organic frameworks were solvothermally synthesized with V-shaped 1,3-bis(1-imidazolyl)benzene (bib) and two Y-shaped carboxylate ligands (1,3,5-benzenetricarboxylic acid (H3btc) and 3,5-pyridinedicarboxylic acid (H2pydc)), namely, {[M2(μ3-OH)(bib)(btc)]·H2O}n (M = Co (1) and Fe (2)) and {[M′2(μ3-OH)(μ2-NO3)(bib)(pydc)]·solvents}n (M′ = Co (3) and Ni (4)). All of them are characterized by single-crystal X-ray diffraction, infrared spectrosopy, and powder X-ray diffraction. Both complexes 1 and 2 present two-dimensional (3,8)-connected layer structures, and the point symbol is (3.42)2(34.46.56.68.73.8), but Fe2 in 2 is weakly coordinated to O5 as a trigonal bipyramidal geometry compared with the tetrahedral Co2 in 1, while complexes 3 and 4 exhibit three-dimensional “pillar-layer” structures with (3,8)-connected tfz-d net. Interestingly, nitrate anions with a rare μ2-η2 coordination mode take part in coordination, and rectangular channels along the c axis exist in 3 and 4. Magnetic stu...

Genuine supramolecular isomers based on Y-shaped pyridinedicarboxylate ligands with distinct topology: 2D 63layer, kgd layer to 3D rtl net

Three genuine supramolecular isomers with an identical formula of [Co(cpna)(H2O)2] (1a, 1b and 1c) [H2cpna = 5-(4′-carboxyl-phenyl) nicotinic acid] have been synthesized by adjusting the relative molar ratio of Y-shaped ligand H2cpna : CoCl2 under solvothermal conditions. Isomer 1a possesses a two-dimensional (2D) 63-hcb layer, in which the central Co(II) adopts trigonal bipyramidal geometry. 1b and 1c contain the same edge-shared dimeric SBUs, which are further ligated by cpna2− ligands to form 2D (3,6)-connected (43)2(46·66·83)-kgd layers and a 3D (3,6)-connected (4·62)2(42·610·83)-rtl net, respectively. The coordination modes of the cpna2− ligand in 1b and 1c are the same, indicating that only the difference in the dihedral angles of the pyridine and phenyl rings contributes to different isomers. Magnetic investigation indicates ferromagnetic interactions between Co(II) ions in edge-shared dimeric SBUs.

Preparation of iron oxide nanoparticles functionalized with Y-shaped ligands for brain tumor targeting.

In this study, we developed functionalized iron oxide nanoparticles for brain tumor targeting. The iron oxide (Fe3O4) particles were stabilized with pluronic F127 and coupled with dopamine-terminated Y-shaped ligands (Tat peptide and transferrin) as a result of the noncovalent conjugation of dopamine (of Y-shaped ligands) and the iron oxide nanoparticles. Here, the hydrophobic domain of pluronic F127 coated on the iron oxide nanoparticles enabled the absorption of a model photosensitizing antitumor drug (chlorin e6) in the core/shell interface of the nanoparticles. The experimental results demonstrated that the Y-shaped ligands on the nanoparticles enabled a significant enhancement of in vitro/in vivo cellular uptake for human primary glioblastoma U87-MG cells as a result of multivalent endocytosis by Y-shaped ligands (transferrin receptor-mediated endocytosis and the following Tat peptide-mediated cellular interaction). Furthermore, the Ce6-loaded nanoparticles showed significant enhancement of in vitro/in vivo photodynamic U87-MG cell ablation under light illumination.

Y-shaped ligand-driven gold nanoparticles for highly efficient tumoral uptake and photothermal ablation.

We report functional gold nanoparticles (AuNP) with antibody-like ligands. These particles consist of Y-shaped ligands and AuNP. Transferrin (Tf) and Tat peptide were linked to each head of a Y-shaped poly(ethylene glycol) (PEG)-containing dopamine at one tail site. Also, Y-shaped ligands (with Tf and Tat peptide) were anchored to the surface of the AuNP as the result of noncovalent conjugation of dopamine and the AuNP. Interestingly, the partial shielding of Tat peptides by large Tf molecules rather improved Tf-mediated endocytosis of the AuNP, while minimizing the natural nonspecific cell interaction of Tat peptides. This system resulted in highly improved in vitro/in vivo tumor-selective uptake over AuNP bearing a single ligand (Tf or Tat peptides). Furthermore, this system resulted in significant enhancement of in vivo photothermal tumor cell ablation under light-irradiation conditions for AuNP. We believe that this design is a promising method to easily modify conventional antibodies or ligands to improve their disease-recognition ability.

Syntheses and solid state structures of hybrid d10 metal–organic frameworks based on methylenediisophthalic acid (H4MDIP)

Four novel hybrid d10 metal complexes [Zn(H2MDIP)(4,4′-bpy)0.5]n1 (4,4′-bpy = 4,4′-bipyridine, H4MDIP = methylenediisophthalic acid), [Zn2(MDIP)(bix)·H2O]n2 [bix = 1,4-bis(imidazol-1-ylmethyl)-benzene], {[Cd(H2MDIP)(H2O)]2·H2O}n3, {[Cd2(MDIP)(H2O)2(en)2]·2H2O}n4 (en = ethylenediamine) based on tetracarboxylate acid were synthesized and their structures were determined by X-ray single-crystal diffraction. Complexes 1–2 are 2D grid and undulated structures with four-coordinated Zn2+ ions, respectively; 3–4 are 2D grid and double-sheet structures with six-coordinated Cd2+ ions, respectively. MDIP in complexes 1 and 3 act as V-shaped and Y-shaped ligands, respectively, yet in 2 and 4 MDIP act as similar X-shaped ligands. Diverse topologies, thermal and luminescent properties of complexes 1–4 have also been investigated.