Amide-based tripodal receptors for selective anion recognition

The binding properties of ethylester derivative of p-tetraphenyl tetrahomodioxacalix[4]arenes (1) towards alkali, alkaline-earth, transition and heavy metal cations using UV-absorption spectrophotometry and ¹H-NMR spectroscopy are reported.     

New P-bridgehead urea-based tripodal anion receptors for H2PO4 recognition

A series of new P-bridgehead tripodal urea-based anion receptors 1-3 bearing phosphine oxide (PO) were synthesized and characterized. Their anion-binding ability was examined by UV-vis, ¹H NMR, ³¹P NMR, and ESI-MS. The results revealed that receptors 1-3 showed good sensitivity, selectivity, and binding affinity for H₂PO₄⁻ over NO₃⁻ and Br⁻, and among them receptor 2 showed the best binding affinity for H₂PO₄⁻ over F⁻, Br⁻, CH₃COO⁻, HSO₄⁻, and NO₃⁻. The Job plot experiments indicated that receptors 1-3 formed 1:1 stoichiometric complex with H₂PO₄⁻.     

Tris-(2-aminoethyl)amine-based tripodal trisindolylureas: new receptors for sulphate

A series of tren-based amide or urea linked tris-indole anion receptors have been synthesised and their anion complexation properties studied in DMSO-d ₆/water mixtures.     

Self-assembly of frameworks with specific topologies: construction and anion exchange properties of M3L2 architectures by tripodal ligands and silver(I) salts

Three five-component architectures, compounds 3, 4, and 5 were obtained by self-assembly of tripodal 1,3,5-tris(imidazol-1-ylmethyl )-2,4,6-trimethylbenzene (6) and 1,3,5-tris(benzimidazol-2-ylmethyl)benzene (7) ligands with silver(I) salts. The structures of these novel complexes have been determined by X-ray crystallography. The results of structural analysis indicate that these frameworks have same M3L2 components, but different structures. Compounds 3 and 4 are both M3L2 type cage-like complexes, while the 5 is an open trinuclear complex. The complex 3 is a cylindrical cage with simultaneous inclusion of a perchlorate anion inside of the cage as a guest molecule. Such guests can be exchanged for other anions through the open edge of the cage as evidenced by crystal structure of 4. The results demonstrate that the molecular M3L2 type cage can act as a host for anions and provide a nice example of supramolecular architectures with interesting properties and possible applications.     

Cobalt complexes with tripodal ligands: implications for the design of drug chaperones

Extensive research is currently being conducted into metal complexes that can selectively deliver cytotoxins to hypoxic regions in tumours. The development of pharmacologically suitable agents requires an understanding of appropriate ligand-metal systems for chaperoning cytotoxins. In this study, cobalt complexes with tripodal tren (tris-(2-aminoethyl)amine) and tpa (tris-(2-pyridylmethyl)amine) ligands were prepared with ancillary hydroxamic acid, β-diketone and catechol ligands and several parameters, including: pK(a), reduction potential and cytotoxicity were investigated. Fluorescence studies demonstrated that only tpa complexes with β-diketones showed any reduction by ascorbate in situ and similarly, cellular cytotoxicity results demonstrated that ligation to cobalt masked the cytotoxicity of the ancillary groups in all complexes except the tpa diketone derivative [Co(naac)tpa](ClO(4))(2) (naac = 1-methyl-3-(2-naphthyl)propane-1,3-dione). Additionally, it was shown that the hydroxamic acid complexes could be isolated in both the hydroxamate and hydroximate form and the pK(a) values (5.3-8.5) reveal that the reversible protonation/deprotonation of the complexes occurs at physiologically relevant pHs. These results have clear implications for the future design of prodrugs using cobalt moieties as chaperones, providing a basis for the design of cobalt complexes that are both more readily reduced and more readily taken up by cells in hypoxic and acidic environments.     

Molecular recognition of fluoride anion: benzene-based tripodal imidazolium receptor

A benzene-based tripodal imidazolium receptor utilizing the strong (C-H)(+)...X(-) hydrogen bonding interaction between imidazolium moieties and halide anions is extensively investigated both theoretically and experimentally. Ab initio calculations predict that this receptor has a very high affinity for fluoride ion (F(-)). The association constant and free energy gain of the N-butyl receptor 2 for F(-) in acetonitrile were measured to be 2.1 x 10(5) M(-1) and -7.25 kcal/mol, respectively, showing that the receptor has a high affinity for F(-) in highly polar organic solvents.     

Structure-activity relationships in tripodal transmembrane anion transporters: the effect of fluorination

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.     

A strategy for the build-up of transition-metal complexes containing tripodal [ArPOS2]2- and [ArPS3]2- ligands (Ar = 4-anisyl)

The investigation presents new synthetic methods for the generation of tripodal P/S ligands by reactions of metal alkoxides and carboxylates with the organoperthiophosphinic acid anhydride Lawesson's reagent. Four new transition-metal complexes containing various tripodal ligand sets were synthesised and characterised.     

Binding of ligands by copolymer globules: Mesoscopic simulation

A simple mesoscopic model of a synthetic ligand-containing copolymer is proposed. Proteinlike copolymers—copolymers containing special sequences that can form globules with a dense solvophobic core and a loose solvophilic corona in solutions—are considered as ligand carriers. It is assumed that solvophilic units contain groups that can coordinate ligands from solution. The binding ability of such copolymers at various chain conformations is studied. It is found that the globular conformation promotes the coordination of ligands. On average, the amount of ligands bound by the copolymer in this conformation is a factor of 3 greater than that in the coil conformation. Apparently, this finding may be explained by the presence of the loose corona, which, on the one hand, provides the increased concentration of solvophilic units and, on the other hand, does not prevent the free diffusion of ligands in it.     

Intermolecular interactions of extended aromatic ligands: the synchrotron molecular structures of [Ru(bpy)2(N-HSB)].2PF6 and [Ru(bpy)2(N-(1/2)HSB)].2PF6

An off-set stack and a saddle-like distortion are revealed by the molecular structures of [Ru(bpy)2(N-HSB)].2PF6 and [Ru(bpy)2(N-(1/2)HSB)].2PF6.     

From molecule to bulk material: optical properties of hydrogen-bonded dimers [C12H12N4O2AgPF6]2 and [C28H28N6O3AgPF6]2 depend on the arrangement of the oxime moieties

The dependence of the optical properties of [C(12)H(12)N(4)O(2)AgPF(6)](2) (dimer-1) and [C(28)H(28)N(6)O(3)AgPF(6)](2) (dimer-2) on the arrangement of the oxime moieties in the molecule and in bulk crystals was investigated by means of time-dependent density functional theory. Dimer-1 with simple pyridine oxime ligands and a wavy arrangement has a smaller dipole moment and larger transition energy between the two states, and thus smaller third-order polarizabilities and two-photon absorption cross sections. Dimer-2 with extended pyridine oxime ligands and a ladder arrangement has a larger dipole moment and smaller transition energy between the two states, and thus larger third-order polarizabilities and two-photon absorption cross sections. The lowest energy absorption band is red-shifted for dimer-2 as compared with dimer-1, due to more pronounced pi-pi delocalization interactions and weaker hydrogen bonding in dimer-2. The electronic absorption spectra, frequency-dependent third-order polarizabilities, and two-photon absorption cross sections involve significant contributions from charge transfers from pi/pi* orbitals of the pyridine oxime ligands but no contribution from PF(6) (-) ions or H(2)O molecules in the wavelength range studied for the monomers and dimers of the C(12)H(12)N(4)O(2)AgPF(6) and C(28)H(28)N(6)O(3)AgPF(6) molecules. The third-order susceptibilities and two-photon absorption coefficients of bulk solids were estimated on the basis of the optical properties of the corresponding dimers, and the bulk material constructed from dimer-2 has the larger optical parameters of the two.     

Spectrophotometric determination of the stability constants of HgCl(-)3 and HgCl(2-)4 in aqueous ethanol

The stability constants of HgCl(-)(3) and HgCl(2-)(4) in 60% aqueous ethanol (v/v) were determined by spectroscopy at 25 degrees and constant ionic strength and acidity; beta(1) was 3 +/- 1 and beta(2) 9 +/-3.     

Syntheses of Ru-S clusters with kinetically labile ligands via the photolysis of [(cymene)3RuS2](PF6)2

Three ruthenium sulfide clusters with labile CH3CN ligands have been photochemically synthesized. Irradiation of [(cymene)3Ru3S2](PF6)2 ([1](PF6)2) in CH3CN gives [(cymene)2(CH3CN)3Ru3S2](PF6)2 ([2](PF6)2), which has been characterized by 1H NMR spectroscopy, ESI mass spectrometry, and chemical reactivity. Treatment of [2](PF6)2 with PPh3 gives [(cymene)2(CH3CN)2(PPh3)Ru3S2](PF6)2 ([3](PF6)2) and [(cymene)2(CH3CN)(PPh3)2Ru3S2](PF6)2 ([4](PF6)2), while treatment with 1,4,7-trithiacyclononane (9S3) gives [(cymene)2(9S3)Ru3S2](PF6)2 ([5](PF6)2). A crystallographic study demonstrated that the Ru3 core in [3](PF6)2, [4](PF6)2, and [5](PF6)2 is distorted with a pair of elongated Ru-Ru bonds. Cyclic voltammetry shows that [3](PF6)2 and [4](PF6)2 undergo two closely spaced reversible one-electron reductions whereas [5](PF6)2 undergoes one irreversible one-electron reduction and one reversible one-electron reduction. Prolonged irradiation of [1](PF6)2 in CH3CN causes decomposition, resulting in the pentanuclear cluster [(cymene)4Ru5S4](PF6)2 ([6](PF6)2).     

Rhenium(I) compounds bound by tripodal ligands of pyridine and N-methylimidazole

The reaction of Re(CO)(5)Br with tris(2-pyridyl)methanol (tpmOH) leads to unexpectedly complex chemistry with three new compounds forming instead of a single product. In compound 1, the tpmOH ligand binds to the metal in the N,N',N'-mode; 2 has tpmO(-) bound in the N,N',O-mode; while 3 is a dimer with the tpmO(-) ligand utilizing each of the four donor atoms to bridge the two metal centers. The analogous methyl ether ligands, tris(2-pyridyl)methoxymethane (tpmOMe) or tris[2-(l-methylimidazolyl)]methoxymethane (timmOMe), each yielded a single product, 4 and 5, respectively, bound in the N,N',N'-mode, and are new leads for potential radiotherapeutic agents. All compounds have been structurally characterized.     

Sequential and selective Buchwald-Hartwig amination reactions for the controlled functionalization of 6-bromo-2-chloroquinoline: synthesis of ligands for the Tec Src homology 3 domain

Src homology 3 (SH3) domains are highly conserved protein-protein interaction domains that mediate important biological processes and are considered valuable targets for the development of therapeutic agents. In this paper, we report the preparation of a range of new 6-heterocyclic substituted 2-aminoquinolines using Buchwald-Hartwig chemistry. 6-Heterocyclic substitution of the 2-aminoquinoline has provided ligands with increased binding affinity for the SH3 domain relative to the lead compound, 2-aminoquinoline, that are the highest affinity ligands prepared to date. The key step in the synthesis of these compounds required a selective Buchwald-Hartwig amination of an aryl bromide in the presence of an activated heteroaryl chloride. The optimization of reaction conditions to achieve the selective amination is discussed and has allowed for cross-coupling with a range of cyclic amines. Introduction of the amino functionality of the 6-heterocyclic 2-aminoquinolines involved additional Buchwald-Hartwig chemistry utilizing lithium bis(trimethylsilyl)amide as an ammonia equivalent.