Franco Ugozzoli

The preparation and properties of a new lipophilic sodium selective ether ester ligand derived from p-t-butylcalix[4]arene

Abstract A new lipophilic cation ligand (2), which shows selectivity for sodium in extraction experiments, has been obtained by the reaction of p-t-butylcalix[4]arene and t-butyl bromoacetate. The X-ray crystal structure determination and 1H and 13C NMR studies show compound (2) in a fixed “cone” structure both in the solid state and in solution. Compound (2) in apolar media strongly encapsulates sodium cation with a 1:1 stoichiometry and is able to separate the tight sodium picrate ion pair in THF.

p-t-Butylcalix[4]arene tetra-acetamide: a new strong receptor for alkali cations [1]

From the reaction ofp-t-butylcalix[4]arene with α-chloro-N,N-diethyl acetamide a new lipophilic ether-amide ligand (2) has been obtained in high yield. Solution studies show (2) to be a very strong cation receptor for alkali cations, especially sodium and potassium. The X-ray crystal structure determination of the free ligand (2) and two potassium complexes (KI and KSCN) shows the calix[4]arene in a fixed ‘cone’ structure and the cation completely encapsulated in a polar cavity of eight oxygen atoms.

Symbolic representation of the molecular conformation of calixarenes

In calixarene chemistry there is a continuous search for new shaping units or substructures useful for molecular recognition or for the binding of ions. The problem of assigning their molecular conformations cannot be dealt with by the use of the dihedral angles as done until now, because this method contains intrinsic ambiguities. The new approach, proposed here, is based on the use of the set ofn pairs of torsion angles (conformational parameters) which involve the flexible part of the calixarene and it is free of ambiguities. Moreover, knowledge of the set of conformational parameters allows one to build straightforwardly three-dimensional molecular models. A symbolic representation of the molecular conformation of any calix[n]arene may be obtained by combining the Schöenflies symbol of the molecular symmetry together with the signs of the conformational parameters.

Synthesis and Structure of ChiralCone Calix[4]arenes Functionalized at the Upper Rim with L-Alanine Units

Synthetic routes were developed to link L-alanine methyl ester or L-alanyl-L-alanine methyl ester at the upper rim of calix[4]arenes blocked in the cone conformation. Several tetra- (3 and 6) and difunctionalized (11 and 12) amino acids containing macrocycles were obtained. Reaction of these compounds with hydrazine gave the corresponding hydrazido derivatives 4, 13, and 14, while the hydrolysis of 3 with LiOH produced the tetraacid 5 whose lithium salt is water soluble at neutral pH. The structural properties of all amino acids containing calix[4]arenes were studied by mono- and bidimensional 1H NMR experiments. The X-ray crystal structure of the difunctionalized receptor 11 shows three different conformations in the solid state, none of them having intrachain hydrogen bonding.

Bridged calix[6]arenes in the cone conformation: New receptors for quaternary ammonium cations

Abstract The synthesis of calix[6]arene crown ethers 3 and 4 has been accomplished for the first time by selective bridging of the parent macrocycles. The alkylation of 3 with α-chloro-N,N-diethyl acetamide produces a compound 6 whose conformational flexibility is strongly reduced and which assumes a cone conformation both in solution and in the solid state. Compound 6 represents a new type of ditopic receptor which binds tetramethylammonium cation in the polar region at the lower rim, showing an association constant Ka=750 M−1 in CDCl3.

Rigidified Calixarenes Bearing Four Carbamoylmethylphosphineoxide or Carbamoylmethylphosphoryl Functions at the Wide Rim

Conformationally rigidified tetraCMPO derivatives have been prepared from calix[4]arene bis(crown ether) 4a in which adjacent oxygens are bridged at the narrow rim by two diethylene glycol links. Acylation of the tetraamine 4c with the CMPO-active ester 5b gave the tetraphosphine oxide 6a, while the tetraphosphinate 6b and the tetraphosphonate 6c were obtained by Arbuzov reaction of tetrabromoacetamido derivative 7 with PhP(OEt)2 or P(OEt)3. The extraction ability of these CMPO derivatives was checked for selected lanthanides and actinides and compared with the analogous compounds 1b, 10b and 10d derived from calix[4]arene tetrapentyl ether. All rigidified bis(crown ether) ligands are more effective extractants than their pentyl ether counterparts and require only 1/10 of the concentration (cL= 10 4M) to obtain the same distribution coefficients, while with CMPO itself a 2,000-fold concentration is necessary. This could be a consequence of a better preorganisation of the ligating functions owing to the rigidity which on the other hand did not change the observed selectivity for americium (DAm/DEu=9-19) and for light lanthanides over heavy ones. NMR relaxivity titration curves show that the complex of Gd3+ with ligand 6a is highly oligomerised in anhydrous acetonitrile over a large range of ligand:metal concentration ratios. Nuclear magnetic relaxation dispersion (NMRD) profiles also showed that large oligomers were formed, and their mean tumbling times were deduced from the Solomon-Bloembergen-Morgan equations. The NMR spectra of dia- and paramagnetic lanthanide complexes with 6a agreed with the presence of two conformers with an elongated calix[4]arene skeleton in which the distances between opposite methylene groups are different. Contrary to what was observed with ligand 2a, the addition of nitrate ions does not labilize the metal complexes, presumably because of the rigidification effect of the ether bridges. Single-crystal X-ray structures were obtained for the active ester 5b and for diphenylphosphorylacetic acid 5a.

Supramolecular Sensing with Phosphonate Cavitands

Phosphonate cavitands are an emerging class of synthetic receptors for supramolecular sensing. The molecular recognition properties of the third-generation tetraphosphonate cavitands toward alcohols and water at the gas-solid interface have been evaluated by means of three complementary techniques and compared to those of the parent mono- and diphosphonate cavitands. The combined use of ESI-MS and X-ray crystallography defined precisely the host-guest association at the interface in terms of type, number, strength, and geometry of interactions. Quartz crystal microbalance (QCM) measurements then validated the predictive value of such information for sensing applications. The importance of energetically equivalent multiple interactions on sensor selectivity and sensitivity has been demonstrated by comparing the molecular recognition properties of tetraphosphonate cavitands with those of their mono- and diphosphonate counterparts.

Biomimetic macrocyclic receptors for carboxylate anion recognition based on C-linked peptidocalix(4)arenes

Two neutral macrobicyclic anion receptors 4 and 6, containing a calix[4]arene in the cone conformation, two l-alanine units, and a 2,6-diacylpyridine or a phthaloyl bridge, are described. The x-ray crystal structure of the acetone complexes of the pyridine containing macrocycle 6 shows the four amide NH groups to be in close proximity to the chiral pocket delimited by the pyridine and one aromatic nucleus of the calix[4]arene. This conformation is also the most stable in acetone-d6 solution, as proven by one- and two-dimensional NMR spectral measurements. Electrospray ionization–MS and 1H NMR experiments reveal that the two ligands strongly bind carboxylate anions in acetone solution. H-bonding interactions between the carboxylate anions and the amide NH groups, together with π/π stacking, are invoked to explain the efficiency and the selectivity of these anion receptors.

Design and self-assembly of wide and robust coordination cages

The self-assembly of a new class of coordination cages formed from two tetrapyridyl-substituted cavitands connected through four square-planar palladium or platinum complexes is reported. The shape of the internal cavity resembles an ellipsoid with a calculated volume of 840 Å3. The four lateral portals have a diameter of about 6 Å, large enough to allow the fast entrance/egress of counterions in solution. The platinum cages 3a,e cannot be disassembled using triethylamine as competitive ligand and they are kinetically stable at room temperature, whereas the palladium cages 3b-d, 3f-h are disassembled and kinetically labile under the same conditions. The different solubility properties of the cage components have allowed the extension of this self-assembly protocol to the liquid–liquid interface.

Rigid cone calix[4]arenes as π-donor systems: complexation of organic molecules and ammonium ions in organic media

One step synthesis of calix[4]arene biscrowns, with a rigid cone structure and alkyl or phenyl groups at the ‘upper rim’, has been performed. The binding ability of these rigidified cone calix[4]arenes 1–4,13 has been evaluated, in apolar organic media, towards neutral organic molecules and ammonium cation salts. Comparison with more flexible analogues 5,6,11 shows that only rigid cone calix[4]arenes are able to complex organic species. The association constants strongly depend on the type of substituents present at the upper rim. The X-ray crystal structure of the endo complex p-cyclohexyl-25,26-27,28-biscrown-3-calix[4]arene 3 with CH3NO2 has been resolved.