An exclusive fluoride receptor: Fluoride-induced proton transfer to a quinoline-based thiourea.

A new quinoline-based tripodal thiourea has been synthesized, which exclusively binds fluoride anion in DMSO, showing no affinity for other anions including, chloride, bromide, iodide, perchlorate, nitrate and hydrogen sulfate. As investigated by 1H NMR, the receptor forms both 1:1 and 1:2 complex yielding the binding constants of 2.32(3) (in log ß1 ) and 4.39(4) (in log ß2 ), respectively; where quinoline groups are protonated by the fluoride-induced proton transfer from the solution to the host molecule. The 1:2 binding is due to the interactions of one fluoride with NH binding sites of urea sites and another fluoride with secondary +NH binding sites within the tripodal pocket. The formation of both 1:1 and 1:2 complexes has been confirmed by the theoretical calculations based on density functional theory (DFT).

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.

Synthesis and anion binding studies of tris(3-aminopropyl)amine-based tripodal urea and thiourea receptors: Proton transfer-induced selectivity for hydrogen sulfate over sulfate.

Tris(3-aminopropyl)amine-based tripodal urea and thiourea receptors, tris([(4-cyanophenyl)amino]propyl)urea (L1) and tris([(4-cyanophenyl)amino]propyl)thiourea (L2), have been synthesized and their anion binding properties have been investigated for halides and oxoanions. As investigated by 1H NMR titrations, each receptor binds an anion with a 1:1 stoichiometry via hydrogen-bonding interactions (NH⋯anion), showing the binding trend in the order of F- > H2PO4- > HCO3- > HSO4- > CH3COO- > SO42- > Cl- > Br- > I in DMSO-d6 . The interactions of the receptors were further studied by 2D NOESY, showing the loss of NOESY contacts of two NH resonances for the complexes of F-, H2PO4-, HCO3-, HSO4- or CH3COO- due to the strong NH⋯anion interactions. The observed higher binding affinity for HSO4- than SO42- is attributed to the proton transfer from HSO4- to the central nitrogen of L1 or L2 which was also supported by the DFT calculations, leading to the secondary acid-base interactions. The thiourea receptor L2 has a general trend to show a higher affinity for an anion as compared to the urea receptor L1 for the corresponding anion in DMSO-d6 . In addition, the compound L2 has been exploited for its extraction properties for fluoride in water using a liquid-liquid extraction technique, and the results indicate that the receptor effectively extracts fluoride from water showing ca. 99% efficiency (based on L2).

Absorption of atmospheric CO2 as carbonate inside the molecular cavity of a new tripodal hexaurea receptor.

A new hexaurea receptor has been synthesized, which absorbs atmospheric CO2 to produce an air-stable solid carbonate complex under normal conditions. Structural analysis of the carbonate complex with this receptor suggests that the carbonate is fully encapsulated within its highly organized intramolecular cavity via 12 strong NH···O bonds in the range of 2.703(3)-2.989(3) Å from six urea units, with each anionic oxygen coordinated via four NH···O bonds with two urea groups.

A synthetic thiourea-based tripodal receptor that impairs the function of human first trimester cytotrophoblast cells.

A synthetic tripodal-based thiourea receptor (PNTTU) was used to explore the receptor/ligand binding affinity using CTB cells. The human extravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. The cell proliferation, migration and angiogenic factors were evaluated in PNTTU-treated CTB cells. The PNTTU inhibited the CTBs proliferation and migration. The soluble fms-like tyrosine kinase-1 (sFlt-1) secretion was increased while vascular endothelial growth factor (VEGF) was decreased in the culture media of CTB cells treated with ≥1 nM PNTTU. The angiotensin II receptor type 2 (AT2) expression was significantly upregulated in ≥1 nM PNTTU-treated CTB cells in compared to basal; however, the angiotensin II receptor, type 1 (AT1) and vascular endothelial growth factor receptor 1 (VEGFR-1) expression was downregulated. The anti-proliferative and anti-angiogenic effect of this compound on CTB cells are similar to the effect of CTSs. The receptor/ligand affinity of PNTTU on CTBs provides us the clue to design a potent inhibitor to prevent the CTS-induced impairment of CTB cells.