Chiroptic behaviour of a chiral guest in an achiral cucurbit[7]uril host

The protonated forms of the chiral molecules (S)- and (R)-N-benzyl-1-(1-naphthyl)ethylamine (BNEAH⁺) form very stable 1:1 guest–host complexes with cucurbit[7]uril in aqueous solution. The stoichiometry and stability constants for the guest–host complexes were determined by ¹H NMR, UV–visible and circular dichroism spectroscopy and electrospray mass spectrometry. The molecular optical rotations of the guests increase in magnitude by about 5-fold upon formation of the {BNEAH·CB[7]}⁺ species. Energy minimized structures of the guests and guest–host complexes indicate changes in the dihedral angles about the stereogenic centre upon ion-dipole and H-bonding interactions between the ammonium hydrogens of the guest and the carbonyl groups of the cucurbituril portals. The increases in the optical rotations are discussed in terms of restricted rotations of the naphthyl groups and in preferential solvation of benzylamine in the cucurbit[7]uril cavity.     

Interaction between tetramethylcucurbit[6]uril with α-furaldehyde-isonicotinyl-hydrazone hydrochloride

Interaction between tetramethylcucurbit[6]uril (TMeQ[6], host) and the hydrochloride salt of α-furaldehyde-isonicotinyl-hydrazone hydrochloride (FIHH⁺, guest) was investigated using X-ray crystallography and spectroscopic methods. X-ray crystallography showed that the π–π stacking effect and hydrogen bonding resulted in the formation of a dumbbell-shaped supramolecule which contained two FIHH⁺@TMeQ[6] host–guest inclusion complexes. The host–guest interaction provided identifiable changes in the vibrational frequencies in the IR spectra. ¹H NMR spectral analysis established a similar interaction model and revealed that TMeQ[6] preferred to include the furan moiety over the pyridine moiety of the FIHH⁺ guest molecule. Absorption spectrophotometric analysis suggested that the host and guest interact in a ratio of 1:1 with a stability constant K _s = (3.52 ± 0.74) × 10⁶ l mol^? 1.pH titration confirmed that the host–guest interaction led to a clear change in the protonation constant of the title guest. Quantum chemical calculations were used to determine the possible mechanism of formation of the dumbbell-shaped complex.     

Solvent extraction and self-assembly of nanosized aggregates of p-tert-butyl thiacalix[4]arenes tetrasubstituted at the lower rim by tertiary amide groups and monocharged metal cations in the organic phase

New p-tert-butyl thiacalix[4]arenes functionalized with morpholide and pyrrolidide groups at the lower rim in cone, partial cone, and 1,3-alternate conformations were synthesized, and their receptor properties for monocharged cations (alkali metal and silver ions) were studied using the picrate extraction method and dynamic light scattering (DLS). To evaluate the ability of the p-tert-butyl thiacalix[4]arene derivatives to recognize metal ions, liquid-liquid extraction of their picrate salts has been carried out in a mutually saturated water-dichloromethane system. The degrees of extraction and the extraction constants for monocharged metal cations (Li⁺, Na⁺, K⁺, Cs⁺) have been determined. The ability of the systems, consisting of host and guest molecules, to self-assembly was proved by DLS using a Zetasizer Nano ZS particle size analyzer. It was shown that all the investigated thiacalix[4]arenes are able to form nanoscale particles with silver cations under the experimental conditions. The pyrrolidide derivative in the cone conformation showed both self-association and aggregation processes with lithium cations. The degree of extraction for all the investigated systems that formed nanoscale aggregates in the organic phase was more than 67% and the extraction constants, log K_ex determined by the picrate extraction method, more than 6.     

Complexation Between (O‐Methyl)6‐2,6‐Helic[6]arene and Tertiary Ammonium Salts: Acid/Base‐ or Chloride‐Ion‐Responsive Host–Guest Systems and Synthesis of [2]Rotaxane

Complexation between (O ‐methyl)₆‐2,6‐helic[6]arene and a series of tertiary ammonium salts was described. It was found that the macrocycle could form stable complexes with the tested aromatic and aliphatic tertiary ammonium salts, which were evidenced by ¹H NMR spectra, ESI mass spectra, and DFT calculations. In particular, the binding and release process of the guests in the complexes could be efficiently controlled by acid/base or chloride ions, which represents the first acid/base‐ and chloride‐ion‐responsive host–guest systems based on macrocyclic arenes and protonated tertiary ammonium salts. Moreover, the first 2,6‐helic[6]arene‐based [2]rotaxane was also synthesized from the condensation between the host–guest complex and isocyanate.     

Structural connectivity of 18-Crown-6/H+/L-tryptophan noncovalent complexes in gas phase and in solution: Delineating host–guest–solvent interactions in solution from gas phase structures

We investigate the structural correlation of noncovalent crown ether/H⁺/L-tryptophan (CR/TrpH⁺) host–guest complexes in the solution phase with those in the gas phase generated through electrospray ionization/mass spectrometry (ESI/MS) techniques. We perform quantum chemical calculations to determine their structures, relative Gibbs free energies, and infrared spectra. We compare the calculated infrared (IR) spectra with the IR multiphoton dissociation (IRMPD) spectra observed for the 18-Crown-6/TrpH⁺ complex by Polfer and co-workers [J. Phys. Chem. A 2013, 117, 1181–1188] for assigning the IR bands. We observe that the carboxyl group remains “naked,” lacking hydrogen bonding with the CR unit in the gas phase, and that this most stable conformer originates from the corresponding lowest Gibbs free energy structure in solution. Based on these findings, we propose that gas phase host–guest complexes directly correlate with those in solution, reinforcing the possibility of obtaining invaluable information about host–guest–solvent interactions in solution from the structure of the host–guest pair in the gas phase.     

The electrochemical behaviour of [Co(sep)]3+ bound with p-sulfonatothiacalix[4]arene and tetracarboxy-p-sulfonatocalix[4]arene in correlation with inclusive and non-inclusive binding modes

The comparative study of the ion-pairing of Co(III) sepulchrate ([Co(sep)]³⁺) with p-sulfonatothiacalix[4]arene and p-sulfonatocalix[4]arene tetracarbonic acid by ¹H NMR and pH-metric data in solution and X-ray data in solid state elucidates pH dependent effect of carboxylate groups on the stoichiometry and the mode of the ion pairing. The electrochemical data of [Co(sep)]³⁺ bound with both calix[4]arenes have been analyzed in the correlation with stoichiometry and the mode of their binding. The pH-dependent effect of tetracarboxy-p-sulfonatocalix[4]arene on the electrochemical behavior of [Co(sep)]³⁺ has been found to correlate with the participation of carboxylate groups in the host?Cguest binding.     

Synthesis of novel pillar-shaped cavitands “Pillar[5]arenes” and their application for supramolecular materials

In 2008, we reported a new class of macrocyclic hosts and named “Pillar[5]arenes”. They combine the advantages and aspects of traditional hosts and have a composition similar to those of typical calix[n]arenes. Pillar[5]arenes have repeating units connected by methylene bridges at the para-position, and thus they have a unique symmetrical pillar architecture differing from the basket-shaped structure of meta-bridged calix[n]arenes. Pillar[5]arenes show high functionality similar to cyclodextrins, and can capture electron accepting guest molecules within their cavity similarly to cucurbit[n]urils. In this review, the synthesis, structure, rotation, host–guest properties, planar chirality and functionality of pillar[5]arenes are discussed, along with pillar[5]arene-based supramolecular architectures and the challenges in synthesizing pillar[6]arenes.     

Thermodynamic aspects of the host-guest chemistry of pyrogallol[4]arenes and peralkylated ammonium cations

The stability constants (K), standard free energy (ΔG^o), enthalpy (ΔH^o), and entropy changes (ΔS^o) for the complexation of pyrogallol[4]arenes with ammonium cations of different size and shape have been determined in ethanol at 298 K by isothermal titration calorimetry. The trends observed in the thermodynamic parameters for 1:1 and/or 1:2 host-guest complexation correspond to the systematic structural changes of the guest molecules. On the basis of the results obtained we compare the complexation properties with two other resorcin[4]arenes and discuss the thermodynamic aspects of this supramolecular host-guest interactions.     

Structure and interaction between the [BMIM][Ala] alanine anion and the 1-butyl-3-methylimidazolium cation in ion pairs

The equilibrium geometries and vibrational frequencies of the ionic liquid 1-butyl-3-methylimidazolium cation and the alanine anion [BMIM][Ala] are studied using density functional theory (DFT) at the B3PW91/6-311+G(d,p) leve1. The most stable structures of the anion, the cation, and the ion pairs are obtained and characterized, and the geometry parameters of the ion pairs confirm the presence of a hydrogen bonding interaction between the anion and the cation. Natural bond orbital (NBO) analysis is also performed to analyze the atomic charge distribution and charge transfer in the [BMIM]⁺ cation and [BMIM][Ala] ionic liquids. The results show that there are the electrostatic interaction and multiple hydrogen bond interactions between the cation and the anion of the ionic liquids, and the stability of the ground state of the ion pairs mostly results from the hydrogen bonding between the lone pairs of O atoms in the anion and H in the imidazole cycle of the cation. There are some changes in microstructures and the charge distribution during the formation of the ion pairs.     

Theoretical insights into the formation, structure, and electronic properties of anticancer oxaliplatin drug and cucurbit[n]urils n = 5 to 8

Geometries, formation and electronic properties of cucurbit[n]uril-oxaliplatin n = 5–8, host-guest complexes are investigated with DFT calculations. The formation of inclusion complexes of CB[n]-oxaliplatin are facile in CB[n] n = 6–8. In the complex, the cyclohexyl group is found to be deep inside the cavity, with the formation of a hydrogen bonding between the portal oxygen atoms and the amine nitrogen of the oxaliplatin guest. NBO analysis shows the transfer of charge from the metal center to the CB[7] unit and the existence of hydrogen bonding between the oxygen portal and amine nitrogen. The HOMO orbital is localized on the carboxylate group and the LUMO orbital are localized on the cucurbituril unit in CB[7]-oxaliplatin complex. The strength of the interaction determined here reflects the ability of CB[n] to act as a host for suitably oxaliplatin guests, even in aqueous solution.     

Synthesis, NMR, X-ray structural analyses and complexation studies of new Ag selective calix[4]arene based dipodal hosts—a co-complexation of neutral and charged species

New podands based on the p-tert-butylcalix[4]arene unit with substitution at the lower rim incorporating imine units, have been synthesized in high yield by simple condensation method. These podands have been shown to extract and transport Ag⁺ selectively over alkali, alkaline earth metal cations, Zn²⁺, Pb²⁺ and Hg²⁺ ions, from neutral aqueous phase to organic phase. In all the ligands the calix unit has been found to be present in a cone conformation except for the one having pyridine as end group, at the ortho position. It has been isolated in two conformations; cone and 1,2-alternate. To the best of our knowledge, this may be the first 1,3-lower rim substituted calix[4]arene to exist in a 1,2-alternate conformation and is among a few known compounds with this conformation in the general class of calix[4]arenes. A complex of this ligand, which happens to be the highest extractant of Ag⁺ has been isolated and characterized using mass, ¹H and ¹³C NMR spectroscopy's and elemental analysis. The spectroscopic evidence and molecular modelling studies performed on the complex suggest a participation of the imine and pyridine nitrogens and two of the ether oxygens in coordination to the metal ion. The X-ray crystal structures of three of the ligands establish the formation of inclusion complexes with polar acetonitrile solvent molecules. The ¹H and ¹³C NMR spectra of all the compounds, taken in CDCl₃, show the presence of acetonitrile molecules in the cavity of the calix[4]arene, indicating inclusion of the neutral guest molecules in the solution phase as well. For one of the podands X-ray crystal structure has shown a formation of clatharate complex of chloroform with the ligand which has rarely been found in the case of calix[4]arenes.     

Clip[5]arenes: A new family of molecular clips

Here we report the design and syntheses of two new triptycene-based rigid acyclic C-shaped hosts, clip[5]arenes C[5]OH and C[5]ME, and the strong host–guest complexation between C[5]OH and an electron-poor bipyridinium salt, paraquat G. The K_a value for the host–guest complex C[5]OH???G was calculated to be (1.09?±?0.36)??×??10⁵?M^?1 in acetone by using a non-linear curve-fitting method based on the UV–vis absorption titration experiments. Furthermore, based on this new host–guest recognition motif, a novel pseudopolyrotaxane-like supramolecular structure was constructed with C[5]OH threaded on polyviologen polymer VP-10.     

Supramolecular self-assemblies of stereoisomers of p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim with some metal cations

Novel p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim in cone, partial cone and 1,3-alternate conformations were synthesized and their receptor properties toward metal ions of p- (Al³⁺, Pb²⁺) and d- (Fe³⁺, Co³⁺, Ni²⁺, Cu²⁺, Ag⁺, Cd²⁺) elements were investigated by picrate extraction and dynamic light scattering (DLS). It was shown that the p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups are effective extractants of soft metal cations. The complex stoichiometry depended on the receptor configuration. All the p-tert-butyl thiacalix[4]arene derivatives with hydrazide fragments were able to form nanoscale aggregates but did not show self-association abilities.     

Reaction from isomeric parent ions in the dissociation of dimethylpyrroles

The major dissociation pathways of the [M-H]⁺ (loss of NH₃ or CH₄) and the [M+H]⁺ (loss of NH₃ or CH₃) ions from dimethylpyrroles have been determined to occur from isomeric parent ions. For the [M-H]⁺ ion (formed by loss of a methyl hydrogen), loss of NH₃ leads to the formation of the phenylium ion and is preceded by consecutive carbon ring expansions followed by a ring contraction to form protonated aniline. Loss of CH₄ occurs after the first carbon ring expansion, which forms protonated picoline. The relative partitioning between the two dissociation paths depends upon the internal energy content of the parent ion; the highest point on the potential energy surface is the second ring expansion step. The [M+H]⁺ ion reacts through a similar pathway via dihydro analogs of picoline and aniline. The proposed reaction pathways are supported by results of semiempirical molecular orbital calculations.     

Molecular dynamics simulation study of the structural features and inclusion capacities of cucurbit[6]uril derivatives in aqueous solutions

Molecular dynamics (MD) simulations were performed for cucurbit[6]uril (CB6) methyl and cyclohexyl derivatives in aqueous solutions. Furthermore, MD simulations have been conducted to study the inclusion complexes between each CB6 derivative with α,ω-pentane diammonium ion (NH₃⁺(CH₂)₅NH₃⁺) to estimate the binding free energies, the complex geometries and the intermolecular forces responsible for complex formation. Results show a complete inclusion of the guest molecule in the cavity of the host for all complexes. Results also indicate that the guest dynamics inside the cavity of the substituted host is similar to that for the unsubstituted host. This demonstrates that the molecular recognition of the host is not affected by the alkyl substitution at the equator. Also, there is an insignificant conformational change of the macrocyclic structure upon inclusion of the guest. Molecular mechanics/Poisson Boltzmann surface area method was used to estimate the binding free energy of each complex. Results indicate that host–guest electrostatic interactions make the largest contribution to the complex binding free energy. Moreover, van der Waals interactions add significantly to the complex stability. The guest molecules show more or less similar binding free energies with the substituted CB6 that exhibits slightly more negative values than unsubstituted CB6 which is proved also by umbrella sampling.     

Crystalline inclusion compounds of lower rim propyl substituted calix[4]arenes featuring different number and positions of the modifying groups

Three lower rim n-propyl substituted calix[4]arenes (1–3) with varied number and position of the modifying groups have been prepared. Inclusion compounds (five species) involving different kinds of guest solvents have been isolated. Their X-ray crystal structures were determined and comparatively discussed using isostructurality calculations. Two of the inclusion compounds obtained (1a and 1b) are polymorphs containing the same host and guest molecules in equal stoichiometric ratio but different Z′ values caused by a phase transition around 140 K. The inclusion compounds 2a and 2b refer to the interesting case of a mixed solvent complex while 3a allows studying the effect of full lower rim n-propyl substitution.     

Ion-molecule reactions in the gas phase. part XXII. Reactivity of the cis- and trans-indanediols with dimethyl ether ions

Specific reactivity of cis- and trans-indanediols has been investigated under dimethyl ether (DME) chemical ionization conditions. Several unusual species, such as [M + 29]⁺ and [M + 27]⁺ ions, are produced in high yield. From DME pressure variations and tandem mass spectrometry experiments (low-energy collisions with Ar and NH₃) including some labeled compounds, it appears that [M + 29]⁺ ions are generated by nucleophilic substitution according to a S_Ni pathway from the proton bound[M + DMEH]⁺ adduct ion. On the other hand, [M + 27]⁺ ions are produced from the covalent [M + DME ? H]⁺ adduct ions via a stepwise process inducing a water loss. This latter dehydration occurs from the adducts prepared by [DME ? H]⁺ attachment to the homobenzylic hydroxy site, which allows internal proton transfer from the charged position to the benzylic hydroxy group, promotingthe loss of water. In addition, trans indanediol labeled with ¹⁸O has been used to obtain evidence for the regioselectivity of both water-loss mechanisms from the benzylic site.     

Structural determination of oxofatty acids by charge-remote fragmentations

A strategy is described to locate the carbonyl position in oxofatty acids by utilizing charge-remote fragmentations of various molecular ions that are desorbed by fast atom bombardment (FAB). Oxofatty acids were cationized with alkali metal ions (Li⁺, Na⁺, K⁺, Rb⁺, and Cs⁺) to form [M+2Met?H]⁺ or alkaline earth metal ions (Mg²⁺, Ca²⁺, Sr²⁺ or Ba²⁺) to form [M+Met?H]⁺ in the gas phase. The cationized acids undergo charge-remote fragmentations upon high-energy activation, giving a product-ion pattern that has a gap corresponding to the oxo position and bordered by two high-intensity peaks. One of the peaks corresponds to an ion that is formed by the cleavage of the C-C bond β to the oxo position and proximal to the charge (β ion), whereas the other is formed from the cleavage of the C-C bond γ to the oxo position and distal to the charge (γ′ ion). The oxo position is easily determined by identifying the gap and the β and γ′ ions. Furthermore, there are two competing patterns of fragments in a CAD spectrum of an oxofatty acid or ester [M+Li]⁺ ion. These arise because Li⁺ attaches to either the oxo or the carboxylic end, as was confirmed by ab initio molecular orbital calculations. The results demonstrate that control of the fragmentation can be guided by an understanding of metal-ion affinities. Collisional activation of the anionic carboxylates gives results that are similar to those for positive ions, showing that the process is not related to the charge status. Collisional activation of [M+H]⁺ ions does not give structural information because the charge migrates, leading to charge-mediated fragmentations.     

Synthesis of nucleobase-calix[4]arenes via click chemistry and evaluation of their complexation with alkali metal ions and molecular assembly

In this study, calix[4]arene derivatives (11–14) bearing a single nucleobase (adenine, thymine, cytosine or guanine) were synthesised via click chemistry. The complexation ability of the synthesised derivatives with alkali metal ions was measured using MALDI-TOF mass spectrometry, and their molecular assembly in CDCl₃ was determined using ¹H NMR. Calix[4]arene derivatives (11–14) formed 1:1 complexes with all alkali metal ions and the rank order for the complexation selectivity was Rb⁺ > Cs⁺ > K⁺ ? Na⁺ > Li⁺. The attachment of nucleobase at the upper rim of calix[4]arene had little effect on its complexation selectivity for alkali metal ions. Thymine-, adenine- and guanine-calix[4]arenes formed self-assembled structures in CDCl₃ via base–base interactions. In addition, adenine-calix[4]arene (11) bound to thymine-calix[4]arene (12) to form a discrete species via Hoogsteen hydrogen bonding.     

Precise analysis of thyroxine enantiomers in pharmaceutical formulation by mobility difference based on cyclodextrin

Identification and determination of chiral pharmaceutical residues is still a challenging analytical puzzle. In this work, a simple, rapid, and effective method for chiral D/L-tetraiodothyronine (T4) separation and quantitative was developed based on host–guest recognition using ion mobility spectrometry-mass spectrometry (IMS-MS). The D/L-T4 enantiomers were mobility separated by their diastereomeric complexes through mixing with cyclodextrin (CD) and metal ions. D/L-T4 was first separated by complexing with host molecule (α-, β-, γ-CD), observing weak peak-to-peak resolution (R_p-p) by the formed binary complex [CD + D/L-T4-H]⁺, and the R_p-p decreased with the CD size increasing. However, the separation effect of D/L-T4 was much improved with the addition of divalent metal ions (G²⁺) by the formed ternary complex [CD + D/L-T4 + G]²⁺. In comparison, α-CD related complexes can possess the best separation effect for D/L-T4 in most cases. Considering the high selectivity, non-toxic, and chemically stable of β-CD, [β-CD + D/L-T4 + Ca]²⁺ was selected for D/L-T4 analysis (R_P-P = 0.764). Whereafter, chemical theoretical conformations for [β-CD + D/L-T4 + H]⁺ and [β-CD + D/L-T4 + Ca]²⁺ were optimized, discovering similar micro-interaction modes between [β-CD + D-T4 + H]⁺ and [β-CD + L-T4 + H]⁺; while with the addition of Ca²⁺, significantly different interaction modes were observed between [β-CD + D-T4 + Ca]²⁺ and [β-CD + L-T4 + Ca]²⁺. And theoretical collision cross section (CCS) trends for the complexes were consistent with that of the experimental results. Additionally, calibration curves were linear within 1.00 to 10⁴ ng mL^?1 with coefficient (R² > 0.99), gaining the limit of detection (LODs) calculation of 0.11 ng mL^?1, and the detection range between D-T4 and L-T4 of 45.6:1 to 1:59.8. Finally, the method was applied for D/L-T4 detection in Levothyroxine tablets, the detection content has good consistency on drug labeling. Because the proposed method exhibited good analytical performance in terms of speed, selectivity, sensitivity, and reproducibility of the measurements, that can be a promising strategy for effective D/L-T4 detection in pharmaceutical industries or other practical samples.