An Ideal C3-Symmetric Sulfate Complex: Molecular Recognition of Oxoanions by m-Nitrophenyl- and Pentafluorophenyl-Functionalized Hexaurea Receptors.
ABSTRACT: The anion-binding properties of two tripodal-based hexaureas appended with the m-nitrophenyl (1) and pentafluorophenyl (2) groups have been studied both experimentally and theoretically, showing strong affinities for sulfate over other inorganic oxoanions such as hydrogen sulfate, dihydrogen phosphate, bicarbonate, nitrate, and perchlorate. The structural analysis of the sulfate complex with 1 reveals that the receptor organizes all urea-binding sites toward the cavity at precise orientations around a tetrahedral sulfate anion to form an ideal C3-symmetric sulfate complex that is stabilized by 12 hydrogen-bonding interactions. The receptor and the encapsulated sulfate are located on the threefold axis passing through the bridgehead nitrogen of 1 and the sulfur atom of the anionic guest. The high-level density functional theory calculations support the crystallographic results, demonstrating that the C3-symmetric conformation of the sulfate complex is achieved due to the complementary NH···O between the receptor and sulfate.
Project description:A thiourea-based tripodal receptor L substituted with 3-nitrophenyl groups has been synthesized, and the binding affinity for a variety of anions has been studied by 1H NMR titrations and nuclear Overhauser enhancement spectroscopy experiments in dimethyl sulfoxide-d6. As investigated by 1H NMR titrations, the receptor binds an anion in a 1:1 binding mode, showing the highest binding and strong selectivity for sulfate anion. A competitive colorimetric assay in the presence of fluoride suggests that the sulfate is capable of displacing the bound fluoride, showing a sharp visible color change. The strong affinity of L for sulfate was further supported by UV-vis titrations and density functional theory (DFT) calculations. Time-dependent DFT calculations indicate that the fluoride complex possesses a different optical absorption spectrum (due to charge transfer between the fluoride and the surrounding ligand) than the sulfate complex, reflecting the observed colorimetric change in these two complexes. The receptor was further tested for its biocompatibility on primary human foreskin fibroblasts and HeLa cells, exhibiting an excellent cell viability up to 100 ?M concentration.
Project description:The recognition of anions by designed receptors has attracted much attention in recent days. In particular, the selective binding of sulfate with artificial receptors is important because of its relevance to many biological and environmental applications. However, the development of organized molecular receptors with high-efficiency for sulfate binding still remains a significant challenge. We report a novel para-phenylene-bridged hexafunctional tripodal receptor that contains a urea-based inner cleft and a thiourea-based outer cleft, providing perfect sites for step-wise binding of two anions within a single cavity. The new receptor was synthesized in a three-step process, and was investigated for its anion binding properties by 1H NMR titrations, 2D NOESY experiments and computational studies. As indicated by solution binding studies, the receptor selectively binds sulfate over other oxoanions, forming a 1:2 stoichiometric complex that is stabilized via strong H-bonding interactions. High-level DFT calculations reveal that the receptor, owing to the enhanced H-bonding ability of thiourea groups, initially encapsulates one sulfate in its thiourea-based outer cleft, followed by a second encapsulation in its urea-based inner cleft. Such a functionalized receptor with the unique combination of urea-based cleft and thiourea-based cleft in a single receptor has not been reported previously.
Project description: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).
Project description:Although the palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl esters has received significant attention, there is a lack of methods that utilize cheap and readily accessible Pd-phosphane catalysts, and can be routinely carried out with high cross-coupling selectivity. Herein, we report the first general method for the cross-coupling of pentafluorophenyl esters (pentafluorophenyl = pfp) by selective C?O acyl cleavage. The reaction proceeds efficiently using Pd(0)/phosphane catalyst systems. The unique characteristics of pentafluorophenyl esters are reflected in the fully selective cross-coupling vs. phenolic esters. Of broad synthetic interest, this report establishes pentafluorophenyl esters as new, highly reactive, bench-stable, economical, ester-based, electrophilic acylative reagents via acyl-metal intermediates. Mechanistic studies strongly support a unified reactivity scale of acyl electrophiles by C(O)?X (X = N, O) activation. The reactivity of pfp esters can be correlated with barriers to isomerization around the C(acyl)?O bond.
Project description:Pentafluorophenyl triazolium carbenes, widely used in NHC-catalysis, can decompose by several mechanisms. Under high concentration conditions, the azolium may undergo a pentafluorophenyl exchange by a proposed SNAr mechanism to give an inactive salt. In the presence of appropriate substrates, cyclization on the ortho-position of the arene can occur, also by SNAr. These adducts provide a potential pathway for catalyst decomposition and serve as a caveat to the development of new reactions and catalysts.
Project description:A phosphate tether-mediated ring-closing metathesis (RCM) study to the synthesis of Z-configured, P-stereogenic bicyclo[7.3.1]- and bicyclo[8.3.1]phosphates is reported. Investigations suggest that C3-substitution, olefin substitution, and proximity of the forming olefin to the bridgehead carbon of the bicyclic affect the efficiency and stereochemical outcome of the RCM event. This study demonstrates the utility of phosphate tether-mediated desymmetrization of C2-symmetric, 1,3-anti-diol-containing dienes in the generation of macrocyclic phosphates with potential synthetic and biological utility.
Project description:A series of easy-to-make fluorinated tripodal anion transporters containing urea and thiourea groups have been prepared and their anion transport properties studied. Vesicle anion transport assays using ion-selective electrodes show that this class of compound is capable of transporting chloride through a lipid bilayer via a variety of mechanisms, including chloride/H(+) cotransport and chloride/nitrate, chloride/bicarbonate, and to a lesser extent an unusual chloride/sulfate antiport process. Calculations indicate that increasing the degree of fluorination of the tripodal transmembrane transporters increases the lipophilicity of the transporter and this is shown to be the major contributing factor in the superior transport activity of the fluorinated compounds, with a maximum transport rate achieved for clog P = 8. The most active transporter 5 contained a urea functionality appended with a 3,5-bis(trifluoromethyl)phenyl group and was able to mediate transmembrane chloride transport at receptor to lipid ratios as low as 1:250000. Proton NMR titration and single crystal X-ray diffraction revealed the ability of the tripodal receptors to bind different anions with varying affinities in a 1:1 or 2:1 stoichiometry in solution and in the solid state. We also provide evidence that the most potent anion transporters are able to induce apoptosis in human cancer cells by using a selection of in vitro viability and fluorescence assays.
Project description:A macrocyclic-based fluorescence chemosensor has been designed and synthesized from the reaction of dansyl chloride and a hexaaminomacrocycle containing four secondary and two tertiary amines. The new chemosensor has been examined for its binding ability toward phosphate, sulfate, nitrate, iodide, bromide, chloride, and fluoride by fluorescence spectroscopy in DMSO. The results indicate that the compound binds each of the anions with a 1:1 stoichiometry, showing high affinity for the oxoanions, chloride and iodide with the binding constants up to four orders of magnitude. Ab initio calculations based on density functional theory (DFT) suggest that the ligand is deformed in order to encapsulate an anion, and each anion, except fluoride, is bonded to the macrocycle through two NH…X(-) and four CH…X(-) interactions.
Project description:With the aim to make the influence of pentafluorophenyl groups in the periphery of high generation dendrons and dendrimers on their NLO performance clearly, some NLO dendrons and dendrimers with different chromophore moieties or different end-capped groups were carefully designed and investigated in detail. The results demonstrated that some strong Ar-Ar(F) interactions between the pentafluorophenyl groups in the periphery and the normal phenyl rings of the donors, could influence the topological structures of dendrons or dendrimers, and then affect their NLO performance. Furthermore, the optical transparency and the stability of the dendrons and dendrimers with pentafluorophenyl groups as end-capped moieties were all improved, in comparison with normal dendrons and dendrimers containing phenyl ones as the end-capped groups.
Project description: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 (1)H NMR, the receptor forms both 1:1 and 1:2 complex yielding the binding constants of 2.32(3) (in log ?1 ) and 4.39(4) (in log ?2 ), 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).