Partial Cone Conformation Research Articles

Synthesis and Structure of Functionalized Homo Heteracalix[2]arene[2]triazines: Effect of All Heteroatom Bridges on Macrocyclic Conformation.

A number of unprecedented homo heteracalix[2]arene[2]triazines were synthesized by means of a fragment coupling approach. Two directional nucleophilic substitution reactions of N-Boc-protected 1,3-dihydrazobenzene with cyanuric acid chloride and 2-butoxy-4,6-dichloro-1,3,5-triazine led to hydrazo-linked trimers, which underwent an efficient macrocyclic condensation reaction with functionalized resorcinol derivatives to afford (NHNBoc)2,O2-calix[2]arene[2]triazine macrocycles, which contain a functional group either on the upper rim or the lower rim. The use of 1,3-phenylenediamines instead of resorcinol in the reaction produced (NR)2,(NHNBoc)2-calix[2]arene[2]triazines. Postmacrocyclization modifications such as a nucleophilic substitution reaction of chloro on triazine by amines and the removal of Boc from hydrazo moieties produced homo calix[2]arene[2]triazine derivatives. In the solid state, (NHNR)2,O2-bridged calix[2]arene[2]triazines with and without a substituent on the upper rim position and (NMe)2,(NHNBoc)2-calix[2]arene[2]triazine adopted a typical partial cone conformation while the heavily twisted 1,3-alternate conformational structures were observed for both (NHNBoc)2,O2-calix[2]arene[2]triazines bearing a functional group on the lower rim position and (NH)2,(NHNBoc)2-calix[2]arene[2]triazine. In solution, all synthesized homo heteracalix[2]arene[2]triazines existed as the mixture of different macrocyclic conformers, which underwent slow interconversions at room temperature relative to the NMR time scale.

Fixing the Conformation of Calix[4]arenes: When Are Three Carbons Not Enough?

Calix[4]arenes are unique macrocycles that through judicious functionalisation at the lower rim can be either fixed in one of four conformations or remain conformationally flexible. Introduction of propynyl or propenyl groups unexpectedly provides a new possibility; a unidirectional conformational switch, with the 1,3-alternate and 1,2-alternate conformers switching to the partial cone conformation, whilst the cone conformation is unchanged, under standard experimental conditions. Using 1 H NMR kinetic studies, rates of switching have been shown to be dependent on the starting conformation, upper-rim substituent, where reduction in bulk enables faster switching, solvent and temperature with 1,2-alternate conformations switching fastest. Ab initio calculations (DFT) confirmed the relative stabilities of the conformations and point towards the partial cone conformer being the most stable of the four. The potential impact on synthesis through the "click" reaction has been investigated and found not to be significant.

Enantiopure Tertiary Urea and Thiourea Derivatives of Trianglamine Macrocycle: Structural Studies and Metallogeling Properties.

Synthesis and detailed experimental and theoretical study on new urea and thiourea derivatives of chiral trianglamine are presented. In solution, the urea derivative of the trianglamine adopts cone conformation, whereas a respective thiourea derivative exists in solution predominantly as a partial cone conformer. In the crystalline phase, the thiourea trianglamine derivative adapts partial cone conformation. In the solid state, the two symmetry independent molecules of thiourea trianglamine create bilayers, containing molecules arranged in a zipper motif. The bilayers are separated by channels filled with disordered solvent molecules. The thiourea derivative of trianglimine appeared to be a simple, low molecular weight supergelator that formed stable chiral metallogels in N,N-dimethylformamide with Ag(I), Cu(I). and Cu(II) salts. The enantiomeric enrichment of the macrocycle is a necessary condition for effective gelling because neither racemic nor enantiomerically enriched samples (up to 50% ee) form metallogels. The metallogels formed from silver cations and thiourea trianglamine show reversible thixotropic property rarely observed in metallogels.

Calix[n]triazoles and Related Conformational Studies.

Calix[n]triazoles are developed as new derivatives in the calixarene family. Calixtriazole compounds 2-4 are synthesized using an iterative convergent strategy including an inter-/intramolecular copper(I)-catalyzed azide-alkyne cycloaddition reaction. Solid-state structures are clearly refined to give 1,2-alternate and partial cone conformations for calix[4]triazole and calix[5]triazole, respectively. Theoretical studies based on density functional theory (DFT) calculations indicated that intermolecular interactions are crucial in determining the conformers of the crystals, and the most stable conformers of calix[4]triazole, calix[5]triazole, and calix[6]triazole in the monomeric forms are 1,3-alternate, 1,3-alternate, and 1,3,5-alternate, respectively.

P-tert-Butylthiacalix[4]arenes functionalized by N-(4'-nitrophenyl)acetamide and N,N-diethylacetamide fragments: synthesis and binding of anionic guests.

New p-tert-butylthiacalix[4]arenes, which are mono-, 1,2-di- and tetrasubstituted at the lower rim containing N-(4’-nitrophenyl)acetamide and N,N-diethylacetamide groups in cone and partial cone conformations have been synthesized. Their complexation ability towards a number of tetrabutylammonium salts n-Bu4NX (X = F−, Cl−, Br−, I−, CH3CO2−, H2PO4−, NO3−) was studied by UV spectroscopy. The effective receptor for the anions studied as well as selective receptors for F−, CH3CO2− and H2PO4− ions, which based on the synthesized thiacalix[4]arenes, have been obtained. It was shown that p-tert-butylthiacalix[4]arene tetrasubstituted at the lower rim by N-(4’-nitrophenyl)acetamide moieties bonded to the anions studied with association constants within the range of 3.55 × 103–7.94 × 105 M−1. Besides, the binding selectivity for F−, Cl−, CH3CO2−, and H2PO4− anions against other anions was in the range of 4.1–223.9. Substituting one or two fragments in the macrocycle with N,N-diethylacetamide groups significantly reduces the complexation ability of the receptor. In contrast to the 1,3-disubstituted macrocycle containing two N-(4’-nitrophenyl)acetamide moieties, the 1,2-disubstituted thiacalix[4]arene, which contains only one such fragment and a N,N-diethylacetamide moiety, selectively binds F− anions.

Smart Polymorphism of Thiacalix[4]arene with Long-Chain Amide Containing Substituents

A problem of controlled (smart) formation of polymorphs was solved for a set of tert-butylthiacalix[4]arene derivatives with four N-(2-acetoxyethyl)carbamoylmethoxy substituents at the lower rim with 1,3-alternate, cone, and partial cone conformations. For this, an effective polymorph screening with a reproducible influence of preparation history was achieved using guest vapor inclusion and a standard state of host glass powder. By this procedure with consequent guest release and heating, the ability of the studied calixarenes for polymorphism was investigated and compared as a function of their macrocycle conformation. The data of simultaneous thermogravimetry and differential scanning calorimetry with mass spectrometry of evolved vapors were determined together with the data of powder X-ray diffraction for the initial host samples, intermediate clathrates, and final polymorphs. In addition, single crystal X-ray diffraction data were obtained for four crystalline forms of the studied calixarenes. The results yielded a structure–property relationship, where 1,3-alternate calixarene without an extended H-bonded supramolecular network at least in one crystalline form has a much higher ability for polymorphism than the other two conformations. Thus, 10 polymorphs with essentially different crystal packing were found for this calixarene including a unique tetramorphism with four consecutive melting points of guest-free polymorph and corresponding three crystallization ranges. This ability of 1,3-alternate calixarene is linked with its other smart property: selective crystallization of its compact glass in vapors of binary liquid mixtures, which can be used for visual detection of very small benzene impurities (0.5% (v/v)) in cyclohexane.

Conformationally Selective Synthesis of Mononitrocalix[4]arene in Cone or Partial Cone

Nitro‐substituted calixarenes in a cone and a partial cone conformation were prepared selectively using distinct synthetic routes. The selective nitration of tris‐ or penta‐substituted phenols of calix[4]arene or calix[6]arene provided mononitrocalix[n]arenes (n = 4, 6). Subsequent addition of ethylene glycol (EG) moieties to mononitrocalix[4]arene provided tetraEGylcalix[4]arene in locked partial cone conformation. By an alternative route – initial addition of EG moieties to the non‐derivatized calix[4]arene followed by the uncontrolled nitration – provided mononitro‐ and dinitro‐tetraEGylcalix[4]arenes locked in the cone conformation. These nitrocalix[4]arenes with locked cone or partial cone conformation are useful building blocks for further assembly of supramolecular systems, especially in the area of material sciences.

Design, synthesis and structure determination of new inherently chiral para-bromoalkoxycalix[4]arenes

The preparative method for the synthesis of inherently chiral para-bromoalkoxycalix[4]arenes based on para-bromination, stepwise regioselective debenzoylation and the following alkylation of the readily available 25-propoxy-26,27-dibenzoyloxycalix[4]arene with propyl bromide or (R)-N-(1-phenylethyl)bromoacetamide has been developed. Three types of the inherently chiral calix[4]arenes in cone or partial cone conformations with asymmetrical (AHHHHBHH, AAHHHBHH, AHBHHCHH) substitution of both upper and lower rims have been obtained in racemic, diastereomerically pure or enantiomerically pure forms. Their structure and the absolute configuration have been determined by NMR and X-ray.

Synthesis of inherently chiral calixarenes via direct mercuration of the partial cone conformation.

Direct mercuration of calix[4]arene immobilized in the partial cone conformation led to the meta-substituted isomer which was subsequently subjected to Pd-catalysed coupling (C-H activation) with the neighbouring aromatic subunit. Regioselective mercuration thus enabled access to a novel type of inherently chiral calixarenes with a highly distorted cavity potentially applicable to the design of new chiral receptors.

Conformational and configurational diversity of solvent inclusion complexes of some calix[4]pyrroles and their anion recognition properties

Sterically hindered meso-tetramethyl-meso-tetraarylcalix[4]pyrroles 1-4 where aryl is p-fluorophenyl 1, p-chlorophenyl 2, and p-methylphenyl 3, 4 (configurational isomers) are synthesized and purified by the recrystallization technique. They are characterized by IR, 1H and 13C NMR, and mass spectroscopy. Configurational isomers ααββ (3) and αααα (4) of meso-tetramethyl-meso-tetramethylphenylcalix[ 4]pyrroles are assigned by the 1H NMR studies and confirmed by the X-ray diffraction analysis. The single crystal X-ray diffraction analysis reveals that the ethanol adduct of 1, the acetone adduct of 2 and 3 adopt the 1,2-conformation while the acetone-water adduct of 1 and the acetone adduct of 4 adopt partial cone and cone conformations respectively. The conformational diversity is due to non-covalent interactions among the encapsulated guest, pyrrolic NH protons, and meso- substituents. Anion binding studies (F–, Cl–, CH3COO–, HSO 4 − ) are carried out through 1H NMR titrations; the binding constants are evaluated using the EQNMR program, displaying that they are more selective towards fluoride rather than other anions with the 1:1 stoichiometry. The configuration of compounds drastically influences the ion-recognition processes.

Synthesis and metal ion extraction of partial-cone di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 ligands with elongated acidic side arms

Proton di-ionizable calix[4]arene-1,2-crown-5 ligands with elongated pendant side arms are synthesized in the partial-cone conformation. Solvent extraction studies probed the influence of elongated side arms and conformation toward various metal cations. Results of the solvent extraction experiments show that these compounds are poor extractants from aqueous solutions into chloroform for hard alkali metal cations and alkaline earth metal cations and intermediate Pb2+. For soft Hg2+, the ligands with N-(X)sulfonyl carbamoyl ionizable groups exhibit very good to excellent extraction efficiency. In general, the metal ion extraction behavior for the new partial-cone conformers is quite similar to that reported recently for their cone conformational isomers.

A Convenient Synthetic Route to Partial-Cone p-Carboxylatocalix[4]arenes

p-Carboxylatocalix[n]arenes have emerged as useful building blocks for the construction of a diverse range of supramolecular assemblies. A convenient route to a p-carboxylatocalix[4]arene that is locked in a partial-cone conformation is presented. The conformation gives the molecule markedly different topological directionality relative to those previously used in self- and metal-directed assembly studies.

Reactivity, aromaticity and absorption spectra of pillar[5]arene conformers: A DFT study

Reactivity and aromaticity of conformers of pillar[5]arene are discussed in the light of DFT and conceptual density functional theory. The absorption spectra of the conformers are analysed using TDDFT (time dependent density functional theory). Reactivity parameters, total electronic energy (Eel), energy of the HOMO (highest occupied molecular orbital, EHOMO), global hardness (η) and electrophilicity (ω) are used to explain the reactivity of the conformers. Aromaticity of the conformers is gauged in terms of nucleus independent chemical shift (NICS). The out of plane component, (NICS)zz values advocate that the conformers are less aromatic compared to benzene. 1,2-alternate and 1,3-alternate conformers showed absorption peaks at higher wavelengths compared to the cone and partial cone conformers.

Ion pair-induced conformational motion in calix[4]arene-strapped calix[4]pyrroles.

In order to understand the still-poorly understood interplay between calix[4]arene conformations and cation and anion recognition in multicomponent systems, the ion pair receptors 1 and 2 were synthesized. In solution and in the solid state, the calix[4]arene subunit of receptor 1 adopts a cone conformation, while that of 2 interconverts between the cone and the partial cone conformation. These geometric features differ from previous systems where the calix[4]arene moiety was locked in the 1,3-alternate conformation. A combination of 1H NMR spectroscopic analyses and single crystal X-ray diffraction studies reveal that receptor 1 binds the fluoride and the chloride anion via significantly different binding modes, displaying, for instance, 1 : 1 and 2 : 3 binding stoichiometries with CsF and CsCl, respectively. In the case of 2, the conformation of the calix[4]arene constituent of 2 is highly dependent on the size and quantity of anions present. For example, upon treatment of 2 with the fluoride anion (as both the TBA+ and Cs+ salts), the calix[4]arene unit coexists as cone and partial cone conformers that are inter-convertible. In the presence of excess CsF, the aromatic rings of the calix[4]arene subunit becomes locked in the pinched cone conformation with the result that an ion pair-mediated coordination polymer is formed. In the presence of excess CsCl, the calix[4]arene unit of 2 adopts only the partial cone conformation stabilized by aryl CH-anion hydrogen bonding interactions. The present systems constitute a rare set of related receptors wherein the effects of conformational changes are so tightly coupled with ion recognition.

Synthesis and Conformational Studies on [3.3.3]Metacyclophane Oligoketone Derivatives, and Their Metal Ion Recognition

Chemical reactions were used to synthesize 2,11,20-tris(ethanedithia)-9,18,27-trimethoxy-6,15, 24-tri-tert-butyl[3.3.3]metacyclophane 2 and 2,11-bis(ethanedithia)-9,18,27-trimethoxy-6,15,24-tri-tert-butyl[3.3.3]metacyclophane 4 from 6,15,24-tri-tert-butyl-9,18,27-trimethoxy[3.3.3]meta-cyclophane-2,11,20-trione 1 and -2,11-dione 3. The yields of 2 and 4 were 70% and 81% respectively. The conformations of the synthesized compounds 2 and 4 were studied using mainly solution Proton Nuclear Magnetic Resonance (1H NMR) spectroscopic methods. Compounds 2 and 4 were found to have a partial-cone conformation. Detailed variable temperature Proton Nuclear Magnetic Resonance studies further confirmed the partial-cone conformation for the two products, 2, 4. During the variable temperature nuclear magnetic resonance spectroscopic studies, compound 2 was found to have a coalescence temperature of about 0?C. Extraction of silver ions with compound 2 gave an extractability of 82% while the parent compound 1 showed zero (0) silver affinity. A 1:1 mol/mol mixture of compound 2 and silver ions studied by solution 1H NMR revealed a novel “Molecular Roulette” type of motion.

A molecular level study of selective cation capture by a host–guest mechanism for 25,26,27,28-tetramethoxycalix[4]arene in MClO4 solution (M = Na, K)

25,26,27,28-Tetramethoxycalix[4] arene selectively captures cations by changing the conformation. In this study, a hybrid approach of ab initio molecular orbital calculation and statistical mechanics for molecular liquid was utilised to understand the capture mechanism in electrolyte solution phase at molecular level. The association free energy and solvation structure were evaluated on the basis of statistical mechanics for molecular liquids. The selectivity is correctly reproduced by the computation, namely cone conformer captures Na+ while K+ is recognised by the partial-cone conformer.

Synthesis of p-tert-butylthiacalix[4]arenes functionalized with tris(2-aminoethyl)amine fragments at the lower rim and their interaction with model lipid membranes

New tetrasubstituted derivatives of thiacalix[4]arene functionalized with tris(2-aminoethyl)amine fragments at the lower rim in the cone, partial cone and 1,3-alternate conformations have been synthesized. It has been shown that during the interaction of tris(2-aminoethyl)amine with thiacalix[4]arenes in cone and partial cone conformation, the cyclic fragments are formed. The structure with acyclic fragments is obtained in the case of thiacalix[4]arenes in 1,3alternate conformation. The interaction of these compounds with a biomembrane model system was studied. It has been shown that the interaction of these compounds with model lipid membranes depends not only on the presence of hydrophilic-hydrophobic groups but also on the spatial orientation of these groups.

Calixradialenes: Calixarene Derivatives with Exocyclic Double Bonds

Reaction of dioxocalix[4]arene 7 with MeLi followed by 2-fold elimination of water yielded calixarene 8 possessing exocyclic double bonds at two adjacent bridges. Calixarene 8 exists in tetrachloroethane-d2 solution at rt, as a 2.3:1 mixture of the 1,3-alternate and partial cone conformers. Keto[n]calixarenes (n = 5, 6) were prepared via hydrolysis of the bromocalixarenes 11 and 12, followed by CrO3 oxidation of the respective hydroxymethylene derivatives. Addition of MeLi to the ketocalix[n]arenes (n = 4, 5 and 6) followed by elimination of water yielded the corresponding calix[n]radialenes. Calix[5]- and calix[6]radialenes adopt in the crystal irregular alternate (i.e., noncone) conformations.

MPW1PW91 study for conformational isomers of methylene bridge-monosubstituted tetramethoxycalix[4]arenes

Structures of ten conformational isomers of methylene bridge-monosubstituted tetramethoxycalix[4]arenes, 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetramethoxy-2-ethylcalix[4]arene (1), and methyl 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetramethoxycalix[4]arene-2-carboxylate (2) were optimized by quantum mechanical mPW1PW91/6-31G(d,p) (hybrid Hartree–Fock density functional) calculations. The total electronic and Gibbs free energies of the various conformations (cone, partial cone, 1,2-alternate, and 1,3-alternate) of 1 and 2 were analyzed. The cone (equatorial) and partial cone (equatorial) conformers were disclosed to be the most stable among all the isomers of 1 and 2. The calculated structures agreed well with the experimental results. The IR spectra were calculated at the mPW1PW91/6-31G(d,p) level for the most stable conformer of each methylene bridge-monosubstituted tetramethoxycalix[4]arene.

Benzimidazole-derived calix[4]arenes with polymerizable styrene groups and their Cu(II) complexes

p-tert-Butylcalix[4]arene [C4(OH)4] was substituted with one to four benzimidazole groups at the phenolic positions affording the compounds C4(OH)3(OBzIm)–C4(OBzIm)4. The solid-state structures confirmed the cone conformation of all derivatives. A tetrasubstituted calix[4]arene with two benzimidazole groups and two 4-methylenestyryl in distal positions C4(OStyr)2(OBzIm)2, which are amenable for polymerization reactions, was also obtained. The monobenzimidazole compound C4(OH)3(OBzIm) reverts to a partial-cone conformation on binding CuCl2, giving rise to the dimeric complex [C4(OH)2(OBzIm)2]2[CuCl(μ-Cl)]2 in the solid state, featuring N and O-coordination from the benzimidazole–N and ethereal–O atoms towards the Cu2+ ions placed outside the calixarene cavity. In contrast, the tetrasubstituted C4(OStyr)2(OBzIm)2 gives rise to the crystallographically-characterized monomeric complex [C4(OStyr)2(OBzIm)2CuCl2], with the cupric ion located directly above the macrocyclic cavity. This complex has 4-methylenestyryl groups at two distal phenolic positions, ideally poised for further modifications, including polymerization of the copper-containing monomer.