Experimental and theoretical studies on halide binding with a p-xylyl-based azamacrocycle.

A p-xylyl-based macrocycle L has been synthesized and its binding properties with halides have been investigated by (1)H NMR titrations, single crystal X-ray diffraction analysis, and density functional theory (DFT) calculations. As investigated by (1)H NMR titrations, the ligand preferentially binds a halide in a 1:2 binding mode, with the association constants (in log K2) of 2.82, 2.70, 2.28, and 2.20 for fluoride, chloride, bromide, and iodide, respectively. The overall binding trend was found to be in the order of fluoride > chloride > bromide > iodide, reflecting that the binding strength correlates with the relative basicity and size of the respective halide. Crystallographic studies indicate that the ligand forms 1:2 complexes with chloride, bromide and iodide. In the chloride complex, the ligand is hexaprotonated and each chloride is held via three NH···Cl(-) bonds. The ligand is tetraprotonated for the other complexes, where each halide is H-bonded to two secondary ammonium NH(+) groups via NH···X(-) bonds. The results of DFT calculations performed on [H6L](6+) at M062x/6-311G (d,p) level in both gas and solvent phases, suggest that the ligand binds halides with the binding energy in the order of F(-) > Cl(-) > Br(-) > I(-), supporting the experimental data obtained from (1)H NMR studies. Results from DFT calculations further indicate that a 1:2 binding is energetically more favorable than a 1:1 binding of the ligand.

Bio-Conjugated Magnetic-Fluorescence Nanoarchitectures for the Capture and Identification of Lung-Tumor-Derived Programmed Cell Death Lighand 1-Positive Exosomes.

As per the American Cancer Society, lung cancer is the leading cause of cancer-related death worldwide. Since the accumulation of exosomal programmed cell death ligand 1 (PD-L1) is associated with therapeutic resistance in programmed cell death 1 (PD-1) and PD-L1 immunotherapy, tracking PD-L1-positive (PD-L1 (+)) exosomes is very important for predicting anti-PD-1 and anti-PD-L1 therapy for lung cancer. Herein, we report the design of an anti-PD-L1 monoclonal antibody-conjugated magnetic-nanoparticle-attached yellow fluorescent carbon dot (YFCD) based magnetic-fluorescence nanoarchitecture for the selective separation and accurate identification of PD-L1-expressing exosomes. In this work, photostable YFCDs with a good photoluminescence quantum yield (23%) were synthesized by hydrothermal treatment. In addition, nanoarchitectures with superparamagnetic (28.6 emu/g), biocompatible, and selective bioimaging capabilities were developed by chemically conjugating the anti-PD-L1 antibody and YFCDs with iron oxide nanoparticles. Importantly, using human non-small-cell lung cancer H460 cells lines, which express a high amount of PD-L1 (+) exosomes, A549 lung cancer cells lines, which express a low amount of PD-L1 (+) exosomes, and the normal skin HaCaT cell line, which does not express any PD-L1 (+) exosomes, we demonstrate that nanoarchitectures are capable of effectively separating and tracking PD-L1-positive exosomes simultaneously. Furthermore, as a proof-of-concept of clinical setting applications, a whole blood sample infected with PD-L1 (+) exosomes was analyzed, and our finding shows that this nanoarchitecture holds great promise for clinical applications.

Highly selective and sensitive macrocycle-based dinuclear foldamer for fluorometric and colorimetric sensing of citrate in water.

The selective detection of citrate anions is essential for various biological functions in living systems. A quantitative assessment of citrate is required for the diagnosis of various diseases in the human body; however, it is extremely challenging to develop efficient fluorescence and color-detecting molecular probes for sensing citrate in water. Herein, we report a macrocycle-based dinuclear foldamer (1) assembled with eosin Y (EY) that has been studied for anion binding by fluorescence and colorimetric techniques in water at neutral pH. Results from the fluorescence titrations reveal that the 1·EY ensemble strongly binds citrate anions, showing remarkable selectivity over a wide range of inorganic and carboxylate anions. The addition of citrate anions to the 1·EY adduct led to a large fluorescence enhancement, displaying a detectable color change under both visible and UV light in water up to 2 µmol. The biocompatibility of 1·EY as an intracellular carrier in a biological system was evaluated on primary human foreskin fibroblast (HF) cells, showing an excellent cell viability. The strong binding properties of the ensemble allow it to be used as a highly sensitive, detective probe for biologically relevant citrate anions in various applications.

Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine Monophosphate (TMP) with a Dinuclear Copper(II) Receptor.

Understanding the intermolecular interactions between nucleotides and artificial receptors is crucial to understanding the role of nucleic acids in living systems. However, direct structural evidence showing precise interactions and bonding features of a nucleoside monophosphate (NMP) with a macrocycle-based synthetic molecule has not been provided so far. Herein, we present two novel crystal structures of uridine monophosphate (UMP) and thymidine monophosphate (TMP) complexes with a macrocycle-based dinuclear receptor. Structural characterization of these complexes reveals that the receptor recognizes UMP through coordinate-covalent interactions with phosphates and π-π stackings with nucleobases and TMP through coordinate-covalent interactions with phosphate groups. Furthermore, the receptor has been shown to effectively bind nucleoside monophosphates in the order of GMP > AMP > UMP > TMP > CMP in water at physiological pH, as investigated by an indicator displacement assay.

Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First Trimester Cytotrophoblast Cells.

The cytotrophoblast (CTB) cells of the human placenta have membrane receptors that bind certain cardiotonic steroids (CTS) found in blood plasma. One of these, marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used synthetic receptors (SR) to study their effectiveness on the angiogenic profile of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. Culture media of CTB cells treated with ≥1 nM SR level revealed sFlt-1 (Soluble fms-like tyrosine kinase-1) was significantly increased while VEGF (vascular endothelial growth factor) was significantly decreased in the culture media (* p < 0.05 for each) The AT2 receptor (Angiotensin II receptor type 2) expression was significantly upregulated in ≥1 nM SR-treated CTB cells as compared to basal; however, the AT1 (Angiotensin II receptor, type 1) and VEGFR-1 (vascular endothelial growth factor receptor 1) receptor expression was significantly downregulated (* p < 0.05 for each). Our results show that the anti-proliferative and anti-angiogenic effects of SR on CTB cells are similar to the effects of CTS. The observed anti angiogenic activity of SR on CTB cells demonstrates that the functionalized-urea/thiourea molecules may be useful as potent inhibitors to prevent CTS-induced impairment of CTB cells.

Crystal structure of bis(bis{(E)-[(6-{(E)-[(4-fluorobenzyl)imino]methyl}pyridin-2-yl)methylidene](4-fluorophenyl)amine}nickel(II)) tetra-bromide nona-hydrate.

In the title complex, [Ni(C21H17F2N3)2]2Br4·9H2O, there are two independent metal complexes per asymmetric unit and two ligands per metal complex. The structural features (bond lengths and angles) of the two complexes are almost identical. In each complex, the nickel(II) ion is coordinated in an octa-hedral environment by six N atoms from two chelating (9E)-N-({6-[(E)-(4-fluoro-benzyl-imino)-meth-yl]pyridin-2-yl}methyl-ene)(4-fluoro-phen-yl)methanammine ligands. The Ni-N bond lengths range from 1.973 (2) to 2.169 (2) Å, while the chelate N-Ni-N angles range from 77.01 (10) to 105.89 (9)°. Additionally, there are four bromide anions and nine solvent water mol-ecules within the asymmetric unit. The water mol-ecules form a hydrogen-bonded network, displaying C-H⋯O, C-H⋯Br, O-H⋯Br, O-H⋯O and O-H⋯F inter-actions into layers parallel to (111). In each unit, the fluoro-phenyl rings of one ligand are stacked with the central ring of the other ligand via π-π inter-actions, with the closest centroid-to-plane distances being 3.445 (5), 3.636 (5), 3.397 (5) and 3.396 (5) Å.

Colourimetric and fluorescent detection of oxalate in water by a new macrocycle-based dinuclear nickel complex: a remarkable red shift of the fluorescence band.

A new macrocycle-based dinuclear nickel chemosensor selectively binds oxalate anions both in solution and the solid state, displaying a remarkable red shift of the fluorescence band with a visible colour change in water at physiological pH in the presence of an external dye.

A highly efficient dinuclear Cu(II) chemosensor for colorimetric and fluorescent detection of cyanide in water.

A novel dinuclear copper chemosensor selectively binds cyanide over a wide range of inorganic anions, enabling it to detect cyanide in water up to 0.02 ppm which is 10 times lower than the EPA standard for drinking water.