Quantum mechanical calculations of conformationally relevant 1H and 13C NMR chemical shifts of calixarene systems

[graphs: see text] QM GIAO calculations of 13C and 1H chemical shift values of the ArCH2Ar group have been performed, using the hybrid DFT functional MPW1PW91 and the 6-31G(d,p) basis set, on some representative calixarenes and on a series of simplified calixarene models allowing derivation of chemical shift surfaces versus phi and chi dihedral angles. A good reproduction of experimental data was obtained. The applicability of chemical shift surfaces in the study of calixarene conformational features is illustrated.     

An NMR Method To Pinpoint Supramolecular Ligand Binding to Basic Residues on Proteins

Targeting protein surfaces involved in protein–protein interactions by using supramolecular chemistry is a rapidly growing field. NMR spectroscopy is the method of choice to map ligand‐binding sites with single‐residue resolution by amide chemical shift perturbation and line broadening. However, large aromatic ligands affect NMR signals over a greater distance, and the binding site cannot be determined unambiguously by relying on backbone signals only. We herein employed Lys‐ and Arg‐specific H2(C)N NMR experiments to directly observe the side‐chain atoms in close contact with the ligand, for which the largest changes in the NMR signals are expected. The binding of Lys‐ and Arg‐specific supramolecular tweezers and a calixarene to two model proteins was studied. The H2(C)N spectra track the terminal CH₂ groups of all Lys and Arg residues, revealing significant differences in their binding kinetics and chemical shift perturbation, and can be used to clearly pinpoint the order of ligand binding.     

Synthesis, Structure, and Complexing Property of p-tert-Butylcalix

p-tert-Butylcalix[4]arene 1,3-digallate, which contains a nonbonded close contact between galloyl groups, was synthesized and its structure was determined by dynamic (1)H NMR and X-ray crystallography. The electronic spectra showed that a new absorption band of the complexes appeared at a longer wavelength region upon adding Ag(+) ion. This spectral shift was explained in terms of the interaction between the facing galloyl groups of the lower rim of the calixarene framework.     

Neutral,Cationic, and Anionic Alkyl Derivatives of Tungsten Bonded to a Calix[4]arene Oxo Surface

The chemically reversible reduction of [(Me)₂W(calix)] to the diamagnetic [(Me)₂W(calix)Na₂] [Eq. (1)], without major changes in the connectivity of the molecule, illustrates the flexibility of the calixarene ligand and stresses its potential as a molecular functional model of heterogeneous oxo surfaces.     

Surface enhanced vibrational (IR and Raman) spectroscopy in the design of chemosensors based on ester functionalized p-tert-butylcalix[4]arene hosts

Surface-enhanced IR (SEIR) and Raman scattering (SERS) have been employed to study the adsorption of ester functionalized tert-butyl calix[4]arenes on Ag and Au nanostructured surfaces as well as their complexes with pyrene. The influence of adsorption and complexation with pyrene on the host calixarene structure was tested for two different calixarene molecules bearing carboethoxy groups (CH(3)CH(2)COOCH(2)-) in the low rim at positions 1,3- and 1,2,3,4-. The results obtained with SEIR were compared to those obtained with SERS, to better understand the interaction mechanism of the studied calixarenes with the metallic surfaces and the ligand as well as to investigate the structure/selectivity relationship of these two surface techniques in the analysis of recognition problems in which these ester functionalized calixarene molecules are involved.     

Bilayers, corrugated bilayers, and coordination polymers of p-sulfonatocalix[6]arene

Exploration into the host-guest supramolecular chemistry of p-sulfonatocalix[6]arene with pyridine N-oxide and 4,4'-dipyridine N,N'-dioxide has resulted in the characterization of three new structural motifs with the calixarene in the "up-down" double partial cone conformation. Two are hydrogen-bonded network structures formed with pyridine N-oxide and either nickel or lanthanide metal counterions (1 and 2, respectively). Complex 1 displays host-guest interactions between pyridine N-oxide and the calixarene in the presence of hexaaquanickel(II) counterions. Complex 2 demonstrates selective coordination modes for different lanthanides involving the calixarene and pyridine N-oxide. The third structure, 3, is a coordination polymer which is formed with 4,4'-dipyridine N,N'-dioxide molecules which span a hydrophilic layer and join lanthanide/p-sulfonatocalix[6]arene fragments. Although complexes 1-3 all have the calixarene in the "up-down" double partial cone conformation, 1 and 3 form bilayer arrangements within the extended structures while 2 forms a previously unseen corrugated bilayer arrangement.     

Energetics of small molecule and water complexation in hydrophobic calixarene cavities

Calixarenes grafted on silica are energetically uniform hosts that bind aromatic guests with 1:1 stoichiometry, as shown by binding energies that depend upon the calixarene upper rim composition but not on their grafted surface density (0.02-0.23 nm(-2)). These materials are unique in maintaining a hydrophilic silica surface, as probed by H2O physisorption measurements, while possessing a high density of hydrophobic binding sites that are orthogonal to the silica surface below them. The covalently enforced cone-shaped cavities and complete accessibility of these rigidly grafted calixarenes allow the first unambiguous measurements of the thermodynamics of guest interaction with the same calixarene cavities in aqueous solution and vapor phase. Similar to adsorption into nonpolar protein cavities, adsorption into these hydrophobic cavities from aqueous solution is enthalpy-driven, which is in contrast to entropy-driven adsorption into water-soluble hydrophobic hosts such as beta cyclodextrin. The adsorption thermodynamics of several substituted aromatics from vapor and liquid are compared by (i) describing guest chemical potentials relative to pure guest, which removes differences among guests because of aqueous solvation and van der Waals contacts in the pure condensed phase, and (ii) passivating residual guest binding sites on exposed silica, titrated by water during adsorption from aqueous solution, using inorganic salts before vapor adsorption. Adsorption isotherms depend only upon the saturation vapor pressure of each guest, indicating that guest binding from aqueous or vapor media is controlled by van der Waals contacts with hydrophobic calixarene cavities acting as covalently assembled condensation nuclei, without apparent contributions from CH-pi or other directional interactions. These data also provide the first direct quantification of free energies for interactions of water with the calixarene cavity interior. The calixarene-water interface is stabilized by approximately 20 kJ/mol relative to the water-vapor interface, indicating that water significantly competes with the aromatic guests for adsorption at these ostensibly hydrophobic cavities. This result is useful for understanding models of water interactions with other concave hydrophobic surfaces, including those commonly observed within proteins.     

Inclusion properties of 3-fluoromesotetraphenylporphyrin with C60 and C70

To improve the selectivity ratio of C70 over C60, a new designer molecule, viz., 3-fluoromesotetraphenylporphyrin (1) has been reported in the present investigations. Fluorescence studies reveal that the Q-absorption band of 1 gets sufficient quenching effect upon addition of both C60 and C70. Binding constants (K) of the C60/1 and C70/1 complexes are estimated to be 580 and 10,800 dm3 mol(-1), respectively. Thus, K(C70)/K(C60) is approximately 19 which is very large and even comparable with other macrocyclic host molecules like calix[5]arene, azacalix[m]arene[n]pyridine, cyclotriveratrylenophane and calixarene bisporphyrin. 1H NMR chemical shift measurements show that the -NH- proton of 1 suffers more shifts in presence of C70 compared to C60. This finding also offers a good support in favor of high K value for C70/1 complex as well as large selectivity ratio of C70 over C60.     

19F Magic angle spinning NMR reporter molecules: empirical measures of surface shielding, polarisability and H-bonding

Magic Angle Spinning (MAS) (19)F NMR spectra have been obtained and chemical shifts measured for 37 molecules in the gas phase and adsorbed on the surfaces of six common materials: octadecyl- and octyl-functionalised chromatography silicas, Kieselgel 100 silica, Brockmann neutral alumina, Norit activated charcoal and 3-(1-piperidino)propyl functionalised silica. From these six surfaces, octadecyl-silica is selected as a non-polar reference to which the others are compared. The change in chemical shift of a fluorine nucleus within a molecule on adsorption to a surface from the gas phase, Deltadelta(gas)(surface), is described by the empirical relationship: Deltadelta(gas)(surface) = delta(s) + (alpha(s)+pi(s))/alpha(r) (Deltadelta(gas)(reference) - delta(r)) + delta(HBA) + delta(HBD), where delta(s) and delta(r) are constants that describe the chemical shift induced by the electromagnetic field of the surface under investigation and reference surface, alpha(s) and alpha(r) are the relative surface polarisability for the surface and reference, pi(s) is an additional contribution to the surface polarisabilities due to its ability to interact with aromatic molecules, and delta(HBA) and delta(HBD) are measurements of the hydrogen acceptor and donor properties of the surface. These empirical parameters are measured for the surfaces under study. Silica and alumina are found to undergo specific interactions with aromatic reporter molecules and both accept and donate H-bonds. Activated charcoal was found to have an extreme effect on shielding but no specific interactions with the adsorbed molecules. 3-(1-Piperidino)propyl functionalised silica exhibits H-bond acceptor ability, but does not donate H-bonds.     

1H and 7Li NMR Study on the Complex Formation of Lithium Cations with Pyridinium Derivatives of Calix[4]arenes

Complexation of lithium ions by three chromoionophoric calix[4]arenes has been studied by ¹H and ⁷Li NMR spectroscopy. The signalling unit of the chromoionophores is the N-methylpyridinium(methyleneimino) group in conjugation with a phenolic group of the calixarene ring while the coordination spheres contain esteric (ethoxycarbonylmethoxy) or etheric (ethoxy, propoxy) units. ¹H NMR and NOESY measurements suggest the dominance of cone conformations of the calixarene rings with slight, solvent-dependent distortions. Complexation occurs only in the presence of a weak base. The interaction with lithium ions causes a broadening of both the ¹H and ⁷Li NMR signals. Analysis of the chemical shifts in the three complexes indicates a different coordination environment for the lithium with the calixarene containing esteric groups from those having etheric groups. This explains the differences in the stabilities of the lithium complexes of the two types of calixarenes.     

含杯芳烃聚合物的合成与应用

杯芳烃在主客体化学中是继冠醚和环糊精之后被广泛关注的第三代主体分子,能够选择性地与客体分子或离子形成络合物。近年来,含杯芳烃聚合物逐渐受到人们的重视。结合聚合物稳定性好,易于加工的特性,含杯芳烃聚合物将有望被开发成为新型功能高分子材料。本文详细介绍了含杯芳烃聚合物的合成及其应用。     

Control of the optical properties of quantum dots by surface coating with calix[n]arene carboxylic acids

A new method for the control of the optical properties of quantum dots (QDs) has been developed using calix[n]arene carboxylic acids (1-3) as surface coating agents for QDs. The calixarene coating of CdSe/ZnS QDs was easily performed in tetrahydrofuran at room temperature. Deprotonation of the carboxyl groups of the calixarene derivatives surrounding the QDs resulted in highly fluorescent water-soluble QDs. The emission peak of the calixarene-coated QDs shifted to longer wavelengths depending on the oligomer size of the calix[n]arene derivative used for the surface coating. Although the red shift of the emission peak decreases with the increase in the particle size of QDs, this surface coating method is useful for the preparation of multi-colored water-soluble QDs from a single-colored hydrophobic QD.     

Synthesis and photochemical reaction of novel p-alkylcalix[6]arene derivatives containing acryloyl or methacryloyl groups

Novel polyfunctional (meth)acrylates with a calixarene backbone [calixarene (meth)acrylates] were synthesized in good yields by certain reactions of p-methylcalix[6]arene (1a) or p-tert-butylcalix[6]arene (1b) with (meth)acrylate derivatives such as acryloyl chloride, methacryloyl chloride, (2-methacryloxy)ethyl isocyanate, and glycidyl methacrylate. Polyfunctional acrylate 6a having poly(oxyethylene) spacer chain between 1a and acrylate groups was also synthesized by the reaction of the poly(oxyethylene) modified 1a with acrylic acid. Calixarene acrylate 6a was liquid at room temperature, although the other calixarene (meth)acrylates were solid at room temperature. The initial decomposition temperature (IDT) of the resulting calixarene (meth)acrylates was measured by the thermogravimetric analysis to evaluate the thermal stability, and it was found that some of the IDTs of the calixarene acrylates were over 400°C. This means that calixarene (meth)acrylates have very good thermal stability. The photopolymerization of the resulting some calixarene (meth)acrylates with (2-phenyoxy)ethyl acrylate as a reactive diluent in the presence of photoinitiator proceeded smoothly upon irradiation with UV light. Therefore, polyfunctional (meth)acrylates with a calixarene backbone can be expected to be novel and thermally stable photoreactive acrylate oligomers. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3071–3078, 1999     

Interactions of a water-soluble calix[4]arene with spermine: solution and solid-state characterisation

Abstract

The octaanionic 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis(hydroxycarbonylmethoxy)-calix[4]arene (cone conformation) (C₄TsTc) was investigated as a sensor for the biogenic tetracationic polyamine, spermine _.(H₄Spe⁴⁺). Fluorescence titration experiments of the water-soluble calixarene with spermine showed the formation of the 2:1 and 1:1 calixarene:spermine complexes in solution. The single crystal X-ray diffraction analysis of [(NaC₄TsTc)₄·(H₄Spe)₇] confirmed the formation of 2:1 and 1:1 calixarene:spermine species and showed that the water-soluble calixarene binds the spermine either by partially hosting it in the inner cavity or through the carboxylate groups on the lower rim. In order to investigate the effect of multivalent systems, supramolecular assemblies of octaanionic calixarene molecules templated by meso-tetrakis(4-N-methylpyridyl)porphyrin (H₂T₄) in different stoichiometric porphyrin:calixarene ratios (1:4 and 3:4) were also tested for spermine binding in solution. Fluorescence titration experiments with the 1:4 and 3:4 H₂T₄:C₄TsTc supramolecular complexes showed that the multivalent assemblies are more sensitive to the presence of spermine than the calixarene alone.     

Synthesis and photochemical reaction of novel p-alkylcalix[n]arene derivatives containing cationically polymerizable groups

New photoreactive p-methylcalix[6]arene (MCA) derivatives containing cationically polymerizable groups such as propargyl ether (calixarene 1), allyl ether (calixarene 2), and ethoxy vinyl ether (calixarene 3) groups were synthesized with 80, 74, and 84% yields by the substitution reaction of MCA with propargyl bromide, allyl bromide, and 2-chloroethyl vinyl ether (CEVE), respectively, in the presence of either potassium hydroxide or sodium hydride by using tetrabutylammonium bromide (TBAB) as a phase transfer catalyst (PTC). The p-tert-butylcalix[8]arene (BCA) derivative containing ethoxy vinyl ether groups (calixarene 4) was also synthesized in 83% yield by the substitution reaction of BCA with CEVE by using sodium hydride as a base and TBAB as a PTC. The MCA derivative containing 1-propenyl ether groups (calixarene 5) was synthesized in 80% yield by the isomerization of calixarene 2, which contained allyl ether groups, by using potassium tert-buthoxide as a catalyst. The photochemical reactions of carixarene 1, 3, 4, 5, and 6 were examined with certain photoacid generators in the film state. In this reaction system, calixarene 3 containing ethoxy vinyl ether groups showed the highest photochemical reactivity when bis-[4-(diphenylsulfonio)phenyl]sulfide bis(hexafluorophosphate) (DPSP) was used as the catalyst. On the other hand, calixarene 1 containing propargyl ether groups had the highest photochemical reactivity when 4-morpholino-2,5-dibuthoxybenzenediazonium hexafluorophosphate (MDBZ) was used as the catalyst. It was also found that the prepared carixarene derivatives containing cationically polymerizable groups such as propargyl, allyl, vinyl, and also 1-propenyl ethers have good thermal stability. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1805–1814, 1999     

Functionalization of the methylene groups of p-tert-butylcalix[4]arene: S-C,N-C,and C-C bond formation

Reaction of the calixarene derivative 7 with two exocyclic double bonds with carbon-, nitrogen-, oxygen-, or sulfur-containing nucleophiles afforded bis(spirodienone) derivatives substituted at two opposite methylene groups in a trans fashion. LiAlH(4) reduction of the bis(spirodienone) derivatives with two methylenes functionalized by thiomethoxy, diethyl malonate, or anilino substituents yielded trans methylene-substituted calix[4]arenes. Upon standing in solution, the calixarene derivative incorporating SMe groups on the bridges underwent trans right harpoon over left harpoon cis isomerization. An equilibration study performed on this calixarene derivative (tetrachloroethane-d(2), 430 K) indicated that the cis isomer is the form of lower free energy.     

Liquid-liquid extraction of transition and alkali metal cations by a new calixarene: Diphenylphosphino calix[4]arene methyl ether

The liquid-liquid extraction of various metal ions by a diphenylphosphino calix[4]arene (1) using picrate counter ion has been studied and compared with those ofp-tert-butyl-calix[4]arene methyl ether (2) and triphenylphosphine (3). The calixarene 1 shows strong binding ability to almost all metal cations examined, but calixarene 2 shows little ability to extract any of them. Based on the continuous variation method, calixarene 1 formed 1: 2 complexes with copper(II) ion.     

On the Role of Flexibility in Protein–Ligand Interactions: the Example of p53 Tetramerization Domain

The recognition of protein surfaces by designed ligands has become an attractive approach in drug discovery. However, the variable nature and irregular behavior of protein surfaces defy this new area of research. The easy to understand “lock‐and‐key” model is far from being the ideal paradigm in biomolecular interactions and, hence, any new finding on how proteins and ligands behave in recognition events paves a step of the way. Herein, we illustrate a clear example on how an increase in flexibility of both protein and ligand can result in an increase in the stability of the macromolecular complex. The biophysical study of the interaction between a designed flexible tetraguanidinium‐calix[4]arene and the tetramerization domain of protein p53 (p53TD) and its natural mutant p53TD‐R337H shows how the floppy mutant domain interacts more tightly with the ligand than the well‐packed wild‐type protein. Moreover, the flexible calixarene ligand interacts with higher affinity to both wild‐type and mutated protein domains than a conformationally rigid calixarene analog previously reported. These findings underscore the crucial role of flexibility in molecular recognition processes, for both small ligands and large biomolecular surfaces.     

Chemical shifts in nucleic acids studied by density functional theory calculations and comparison with experiment

NMR chemical shifts are highly sensitive probes of local molecular conformation and environment and form an important source of structural information. In this study, the relationship between the NMR chemical shifts of nucleic acids and the glycosidic torsion angle, χ, has been investigated for the two commonly occurring sugar conformations. We have calculated by means of DFT the chemical shifts of all atoms in the eight DNA and RNA mono-nucleosides as a function of these two variables. From the DFT calculations, structures and potential energy surfaces were determined by using constrained geometry optimizations at the BP86/TZ2P level of theory. The NMR parameters were subsequently calculated by single-point calculations at the SAOP/TZ2P level of theory. Comparison of the (1) H and (13) C?NMR shifts calculated for the mono-nucleosides with the shifts determined by NMR spectroscopy for nucleic acids demonstrates that the theoretical shifts are valuable for the characterization of nucleic acid conformation. For example, a clear distinction can be made between χ angles in the anti and syn domains. Furthermore, a quantitative determination of the χ angle in the syn domain is possible, in particular when (13) C and (1) H chemical shift data are combined. The approximate linear dependence of the C1' shift on the χ angle in the anti domain provides a good estimate of the angle in this region. It is also possible to derive the sugar conformation from the chemical shift information. The DFT calculations reported herein were performed on mono-nucleosides, but examples are also provided to estimate intramolecularly induced shifts as a result of hydrogen bonding, polarization effects, or ring-current effects.