Hydrogen bonding receptors of tetraamide derivatives derived from thiacalix[4]arene in cone- and 1,3-alternate conformation

Novel ditopic receptors of tetraamide derivatives possessing four 2-pyridyl groups derived from thiacalix[4]arene in cone- and 1,3-alternate conformation were prepared. The structure of one of the tetraamide derivatives was confirmed by a single crystal X-ray analysis. The tetrathiacalix[4]arene tetraamides show strong intramolecular hydrogen bonding. The binding behaviour towards Ag⁺ and halides has been investigated by ¹H NMR titration experiments.     

Synthesis and conformational evaluation of p-tert-butylthiacalix[4]arene-crowns

Bridging of p-tert-butylthiacalix[4]arene afforded 1,3-dihydroxythiacalix[4]arene-monocrown-5 (3b), 1,2-alternate thiacalix[4]arene-biscrown-4 and -5 (4a,b), and 1,3-alternate thiacalix[4]arene-biscrown-5 and -6 (5a,b), depending on the metal carbonates and oligoethylene glycol ditosylates used. Starting from 1,3-dialkylated thiacalix[4]arenes, the corresponding bridging reaction gave 1,3-alternate, partial-cone, and cone conformers 10-19, depending on the substituents present. Temperature-dependent studies revealed that the conformationally flexible 1,3-dimethoxythiacalix[4]arene-crowns 10a-c exclusively occupy the 1,3-alternate conformation. Demethylation exclusively gave the cone 1,3-dihydroxythiacalix[4]arene-crowns (3a,c), which could not be obtained by direct bridging of thiacalix[4]arene. The different structures were assigned on the basis of several X-ray crystal structures and extensive 2-D (1)H NMR studies.     

Alkyl-malonate-substituted thiacalix[4]arenes as ligands for bottom-up design of paramagnetic Gd(III)-containing colloids with low cytotoxicity

The present work introduces thiacalix[4]arene adopting 1,3-alternate conformation with alkyl-malonate terminal substituents as ligands for Gd(III) ions. pH-dependent complex formation of Gd(III) ions via alkyl-malonate substituents in aqueous DMSO solutions results in a precipitation. The precipitated complexes were converted into hydrophilic colloids of “plum-pudding” morphology, where the Gd(III) complexes form hard small (1.5–4 nm) cores included into larger (about 180 nm) soft PSS shells. The precipitate-to-colloid transformation is facilitated by polystyrolsulfonate (PSS) for Gd(III) complexes with thiacalix[4]arene bearing propyl-malonate groups, while the presence of PSS triggers a dissolution of the precipitated complexes for thiacalix[4]arenes with pentyl-malonate substituents. To a lesser extent the similar tendency disturbs the formation of PSS-stabilized colloids on the basis of butyl-malonate substituted thiacalix[4]arene. The PSS-stabilized colloids exhibit high longitudinal and transverse relaxivities (r₁ = 23.8 and r₂ = 29.4 mM⁻¹ s⁻¹ at 0.47 T, respectively), while the recoating of the PSS-stabilized colloids with polyethyleneimine is accompanied by the dissolution of the hard cores. High relaxivity along with low cytotoxicity of PSS-stabilized colloids indicates their applicability as contrast agents in MRI.     

Aminolysis of p-tert-butyltetrathiacalix[4]arene tetraethylacetates in cone, partial cone and 1,3-alternate conformation: synthesis of amide based receptors for oxyanions

Cone, partial cone and 1,3-alternate conformers of tetrathiacalix[4]arene tetraethylacetate were synthesized and subjected to aminolysis with alkyl amines [CH₃(CH₂)_nNH₂; n=2, 3, 5] to yield mono-, di-, tri- or tetrasubstituted p-tert-butyltetrathiacalix[4]arene amides which were characterized by detailed analysis of their NMR spectral and single crystal X-ray crystallography. It has been observed that while the 1,3-alternate and cone conformers of the tetrathiacalix[4]arene tetraethylacetate gave corresponding tetrathiacalix[4]arene tetraamides under different experimental conditions, the corresponding partial cone conformer undergoes a cascade of regioselective reactions with the same amines. Variable temperature ¹H NMR experiments allowed the determination of relative stability of different conformers within the temperature range of 298-333 K. The synthesized derivatives were evaluated as molecular extractants for cations and anions and were determined to facilitate extraction of oxyanions (CrO₄²⁻ and Cr₂O₇²⁻) from aqueous to the organic phase. The studies have a significance in the design of tetrathiacalix[n]arene based molecular receptors for innovative applications.     

Effect of copper(I) on the conformation of the thiacalixarene platform in azide-alkyne cycloaddition

New lower-rim tetrasubstituted p-tert-butylthiacalix[4]arene derivatives bearing alkyl, propargyl, or triazole-containing substituents were synthesized. The structures of these compounds were determined by 1D and 2D NMR spectroscopy in solution and by X-ray diffraction in the solid phase. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) of azides to a mixture of 1,3-alternate–partial cone stereoisomers of dipropargyl derivatives of thiacalix[4]arene affords triazole-containing products exclusively in the 1,3-alternate conformation.     

The influence of heteroatoms on the conformational properties of heteracalix[4]arenes. Comparison of oxygen-, sulfur-, and nitrogen-bridged [14]metacyclophanes

Oxygen- and sulfur-bridged calix[4]arenes have been synthesized by the nucleophilic aromatic substitution of 1,5-difluoro-2,4-dinitrobenzene with 4,6-diisopropylresorcinol or 4,6-diisopropyl-1,3-benzenedithiol. X-ray crystal structure analyses revealed that the oxacalix[4]arene 2 adopts an unsymmetrical 1,3-alternate conformation and that the dinitrobenzene rings strongly conjugate with the bridging oxygen atoms. On the other hand, the thiacalix[4]arene 3 adopts a heavily twisted unsymmetrical 1,3-alternate conformation, and the conjugation is very weak. In the ¹H NMR spectrum (CDCl₃, 30 °C), both compounds display a pair of diastereotopic methyl signals for the isopropyl groups in agreement with the frozen 1,3-alternate conformation on the NMR time scale. The free energies of activation of the macrocyclic inversion for 2 and 3 were determined to be 69.5 kJ mol⁻¹ and 74.9 kJ mol⁻¹, respectively, by variable temperature NMR spectroscopy.     

Hard–Soft Receptors, Tetrakis[(N,N-diethylaminocarbonyl)methoxy] thiacalix[4]arene Derivatives with cone and 1,3-alternate Conformation

Direct O-alkylation of p-tert-butyltetrathiacalix[4]arene with N,N-diethylchloroacetamide afforded two conformational isomers (1,3-alternate and cone) of tetrakis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene and 1,3-disubstituted bis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene, depending on the base used. The complaxation behaviors of the tetrakis isomers were assessed by ¹H NMR titration experiments. Evidence of 1:2 (homo- and hetero-dinuclear) complexes formation of 1,3-alternate-tetrakis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene with alkali (K⁺ and Na⁺) or transition (Ag⁺) metal ions was obtained. Interestingly, it was found that the cone-tetrakis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene required a prior Ag⁺ complexation to form 1:2 heterodinuclear complex. Received in final form: 26 January 2005     

Cation control on the synthesis of p-t-butylthiacalix[4](bis)crown ethers

Bridging of p-t-butylthiacalix[4]arene with ethylene glycol ditosylates gave diametrically bridged thiacalix[4]monocrowns-4 and -5, 1,2-alternate thiacalix[4]biscrowns-4 and -5 and 1,3-alternate thiacalix[4]biscrown-5, dependent on the metal carbonate used. They show excellent extraction ability towards Ag⁺ cations.     

Synthesis,crystal structure and complexation behaviour of a thiacalix[4]arene bearing 1,2,3-triazole groups

The structure and complexation behaviour of 1,3-alternate-1,2,3-triazole based on thiacalix[4]arene,1,3-alternate-1 and 2 have been determined by means of X-ray analysis, fluorescence and ¹H NMR spectroscopy. The X-ray results suggested that the nitrogen atom N3 on triazole ring can act as hydrogen bond acceptors in the self-assembly of a supramolecular structure. The fluorescence spectra changes indicated that the thiacalix[4]arene bearing 1,2,3-triazole groups were highly selective for Ag⁺ in comparison with other tested metal ions by enhancement of the monomer emission of pyrene. The ¹H NMR results suggested that Ag⁺ can be strongly bonded by the triazole groups with the cooperation of the ionophoric cavity formed by the two inverted benzene rings and the sulfur atoms of the thiacalix[4]arene.     

Aminopyridyl derivative of thiacalix[4]arene-carboxylic acid as ionizable highly selective Ag+ ionophore

A novel mono-ionizable receptor 2 possessing three aminopyridyl and one carboxylic group in 1,3-alternate conformation based on thiacalix[4]arene, confirmed by single crystal X-ray analysis, was prepared. For competitive solvent extraction of alkali metal (Na⁺, K⁺ and Cs⁺) and some transition metal (Cu²⁺, Zn²⁺, TI⁺, Ag⁺) cations from aqueous solutions into chloroform, it was found that the introduction of proton-ionizable group (carboxylic acid moiety) into the aminopyridyl-thiacalix[4]arene derivative could further improve its Ag⁺ extractability with high selectivity.     

Informational rigidity in mesitylene-based calix[4]arenes adopting a 1,3-alternate conformation

Two chiral derivatives of a mesitylene-based calix[4]arene known to exist in the 1,3-alternate conformation were prepared by the attachment of homochiral residues to the four exo-hydroxy groups. Thus, the enantiotopic protons of the central scaffold became diastereotopic, leading to a doubling of their ¹H NMR signals in one example. From the temperature independence of the NMR spectrum, a lower limit of 24.2 kcal/mol could be estimated for the barrier of ring inversion. MM3 calculations confirm the 1,3-alternate conformation as the energy minimum, and estimate a barrier of 25.7 kcal/mol for the 1,3-alternate-to-1,3-alternate* interconversion process. This high barrier is due to the repulsive steric interactions between exo-methyl groups at vicinal rings when these groups pass each other.     

Cesium ion-selective electrodes based on 1,3-alternate thiacalix[4]biscrown-6,6

Four thiacalix[4]biscrown ethers with 1,3-alternate conformation were examined for the potentiometric responses in poly(vinyl chloride) membrane electrodes. Their potentiometric selectivities toward potassium and cesium ions over other alkali, alkaline earth, and transition metal ions were measured by the fixed interference method (FIM). Among the ionophores, 1,3-alternate thiacalix[4]biscrown-6,6 showed a high selectivity for cesium over potassium ion and so was optimized as a Cs⁺-selective electrode. The electrode exhibited a linear response with a near Nernstian slope of 57.6 mV per decade in the concentration range of 1.0×10⁻⁶ to 3.2×10⁻² M. It was suitable for use in aqueous solution in a wide range of pH 2.5-12.5 and had a fast response time of ca. 5 s. On the basis of 1,3-alternate thiacalix[4]biscrown-6,6, the electrode has a wide linear range and selectivity for cesium ion over potassium ion better than those previously reported with other ionophores.     

Synergistic extraction of cesium,strontium, and europium with adamantylated thiacalix[4]arenes in the presence of chlorinated cobalt dicarbollide

Synergistic extraction of long-lived fission products ¹³⁷Cs⁺, ⁸⁵Sr²⁺, and ¹⁵²Eu³⁺ from dilute HNO3 into dichloroethane with ligands derived from p-(1-adamantyl)thiacalix[4]arene in mixtures with chlorinated cobalt dicarbollide was studied. An extraordinary synergistic effect is observed in extraction of europium with p-(1-adamantyl)thiacalix[4]arene tetraacetate derivative. Amides of p-(1-adamantyl)thiacalix-[4]arene tetracarboxylic acid are selective toward europium, although their extraction ability toward the examined ions is lower than that of the classical extractant, p-(1-adamantyl)calix[4]arene tetracarboxylic acid diethylamide.     

Structure and conformational equilibrium of thiacalix[4]arene by density functional theory

Density functional theory calculations for the structure and conformational equilibrium of thiacalix[4]arene are reported. The conformational equilibrium of thiacalix[4]arene, a heterocalixarene in which the phenol groups are bridged by sulphur atoms is compared to the conformational equilibrium of calix[4]arene. Thiacalix[4]arene conformational energies relative to the cone conformer (ΔE's) are reduced in comparison with calix[4]arene. This conformational change is in qualitative agreement with recent NMR spectroscopy measurements of the conformational equilibrium for a tetraethylether of thiacalix[4]arene in a CDCl₃ solution which indicates an enhanced chemical exchange of thiacalixarene conformers in comparison with similar methylene bridged structures. Density functional theory results for the structure of thiacalix[4]arene are in good agreement with recent X-ray diffraction measurements. The electrostatic potentials in the cone conformers of thiacalix[4]arene and calix[4]arene suggest that their complexation or recognition abilities can be significantly different. Dipole moments of the four thiacalix[4]arene conformers are in the order: cone>1,2-alternate>partial-cone>1,3-alternate.     

Allosteric bindings of thiacalix[4]arene-based receptors with 1,3-alternate conformation having two different side arms

A novel ditopic receptor possessing two complexation sites such as crown ether and 2-pyridylmethyl groups bearing 1,3-alternate conformation based on thiacalix[4]arene was prepared. The binding behaviors with Li⁺ and Ag⁺ have been examined by ¹H NMR titration experiment. The exclusive formation of mononuclear complexes of 1,3-alternate-5 with Li⁺ and Ag⁺ was observed even though the formation of the heterogeneous dinuclear complexes was expected. The decomplexation of Li⁺ from the crown moiety of 1:1 complex 1,3-alternate-5?Li⁺ to form the Ag⁺?1,3-alternate-5 complex by addition of AgSO₃CF₃ clearly shows that pyridyl moiety works as an efficient switch-off of the recognition ability of the crown moiety. We have also developed the construction of hydrogen-bonding self-assembly heterodimeric systems based on bis(4-pyridyl) and dicarboxylic acid thiacalix[4]arene derivatives in 1,3-alternate conformation. Their supramolecular behaviors are studied by ¹H NMR titration experiments with K⁺ and Ag⁺ ions. Although the values of the dimerization constants are relatively small, the stability of the dimers is strong enough to overcome only small conformational changes upon complex formation.     

Synthesis and evaluation of a novel pyrenyl-appended triazole-based thiacalix[4]arene as a fluorescent sensor for Ag ion

New fluorescent chemosensors 1,3-alternate-1 and 2 with pyrenyl-appended triazole-based on thiacalix[4]arene were synthesized. The fluorescence spectra changes suggested that chemosensors 1 and 2 are highly selective for Ag⁺ over other metal ions by enhancing the monomer emission of pyrene in neutral solution. However, other heavy metal ions, such as Cu²⁺, and Hg²⁺ quench both the monomer and excimer emission of pyrene acutely. The ¹H NMR results indicated that Ag⁺ can be selectively recognized by the triazole moieties on the receptors 1 and 2 together with the ionophoricity cavity formed by the two inverted benzene rings and sulfur atoms of the thiacalix[4]arene.     

Synthesis of unique cagelike thiacalix[4]arene derivatives in a 1,3-alternate conformation

A novel type of doubly bridged thiacalix[4]arenes in the 1,3-alternate conformation has been prepared by direct aminolysis reaction of easily accessible thiacalix[4]arene tetraacetates with alpha,omega-diamines. Despite the high excess of diamine, both sites of a 1,3-alternate conformer can be intramolecularly bridged to form the cagelike structures in high yields. Optimum results were obtained using 1,2-ethanediamine as bridging units. X-ray analysis of the novel cagelike molecules revealed a highly preorganized array of -C(O)-NH- bonds pointing to the interior of the cavity.     

Novel dendritic cores based on thiacalix[4]arene derivatives

Thiacalix[4]arenes possessing carboxylic groups were used for the design of potential dendritic cores with amino surface groups. The known tetraacetic acid in the 1,3-alternate conformation gave the desired product in very low yield because of steric hindrance on thiacalix[4]arene moiety. Therefore, synthetic strategy based on withdrawing of the carboxyl groups via benzylic spacer from the thiacalix[4]arene moiety was successfully applied for the realization of novel thiacalix[4]arenes bearing two or four protected lysine units.     

Thiacalix[4]arene based reconfigurable molecular switches: set-reset memorized sequential device

The fluorescent chemosensors 3, 5 and 7 based on thiacalix[4]arene bearing naphthyl groups have been designed and synthesized. The optical chemosensor 3 based on a thiacalix[4]arene of cone conformation behaves as "turn-on" optical chemosensor for Fe(3+) and F(-) ions. However, chemosensors 5 and 7 based on a thiacalix[4]arene of 1,3-alternate conformation demonstrate "turn-on" optical behaviour for Hg(2+), F(-) ions (with receptor 5 as turn-on for K(+) ions also) and "turn-off" behaviour for Fe(3+) ions. The simultaneous presence of Fe(3+) and Hg(2+) or K(+) or F(-) ions results in formulation of reversible "on-off" switches. Various molecular logic gates developed in response to molecular switching between these chemical inputs have been integrated into sequential logic circuits with memory function in a feedback loop which mimics "set-reset" molecular level information processing device.     

Anion receptors based on ureido-thiacalix[4]arenes

The regioselective ipso-nitration of tert-butylthiacalix[4]arene-tetrasulfone was used for the construction of thiacalixarene derivatives bearing one or two arylureido functions on the upper rim. The preorganization of ureido units using the thiacalix[4]arene moiety as a molecular scaffold leads to novel anion receptors with good complexation ability toward selected anions of various geometry (halides, carboxylates, HSO₄⁻, H₂PO₄⁻, NO₃⁻, CN⁻) in organic solvents.