Fluorescence study of inclusion complexes between star-shaped cholic acid derivatives and polycyclic aromatic fluorescent probes and the size effects of host and guest molecules

Star-shaped host molecules containing two, three, and four cholic acid moieties have been used to form inclusion complexes with polycyclic aromatic hydrocarbon probes (guests) varying in size from four (pyrene) to five (benzo(e)pyrene) and seven aromatic rings (coronene) and investigated by steady-state fluorescence measurements and fluorescence lifetime techniques. The results indicated that these hydrophobic guest probes prefer to locate in the hydrophobic cavities formed by the host molecules in an aqueous solution. Further studies showed that the stoichiometric ratios of the complexes depended on the relative size of both the host and the guest. The complexes of 1:1 ratio (guest:host) were formed between pyrene and the host molecules of different sizes, while the complexes of 1:2 ratio (guest:host) were found for coronene in all cases. For benzo(e)pyrene with an intermediate size, the complexes with 1:1 and 1:2 ratios (guest:host) were formed depending on the relative sizes of the host molecules. The stability of the inclusion complexes was observed to change with the solvent polarity, indicative of an adaptation of the hydrophobicity of the host pockets to the polarity of the solvent. The formation of the complexes was driven by the solvophobic interactions.     

Guest-dependent complexation of triptycene-based macrotricyclic host with paraquat derivatives and secondary ammonium salts: a chemically controlled complexation process

The triptycene-based macrotricyclic host containing two dibenzo-[24]-crown-8 moieties has been found to form stable 1:1 or 1:2 complexes in different complexation modes with different functional paraquat derivatives and secondary ammonium salts in solution and in the solid state. Consequently, the alkyl-substituted paraquat derivatives thread the lateral crown cavities of the host to form 1:1 complexes. It was interestingly found that the paraquat derivatives containing two beta-hydroxyethyl or gamma-hydroxypropyl groups form 1:2 complexes, in which two guests thread the central cavity of the host. Other paraquat derivatives containing terminal hydroxy, methoxy, 9-anthracylmethyl, and amide groups were included in the cavity of the host to form 1:1 complexes. Moreover, the host also forms a 1:2 complex with two 9-anthracylmethylbenzylammonium salts, in which the 9-anthracyl groups were selectively positioned outside the lateral crown cavities. The competition complexation process between the host and two different guests (the propyl-substituted paraquat derivative and a dibenzylammonium salt) could be chemically controlled.     

Synthesis of triptycene-derived macrotricyclic host containing two dibenzo-[18]-crown-6 moieties and its complexation with paraquat derivatives: Li(+)-ion-controlled binding and release of the guests in the complexes

A new triptycene-derived macrotricyclic host containing two dibenzo-[18]-crown-6 moieties was synthesized and shown to form 1:1 complexes with paraquat derivatives in solution, in which the guests all thread the central cavity of the host. However, it was interestingly found that, depending on the paraquat derivatives with different functional groups, the host can form stable 1:1 or 1:2 complexes in different complexation modes in the solid state, which is significantly different from those of the macrotricyclic host containing two dibenzo-[24]-crown-8 moieties. The formation of the complexes was also proved by the ESI MS and electrochemical experiments. Moreover, it was found that the binding and release of the guests in the complexes could be easily controlled by the addition and removal of lithium ions.     

A H NMR study on the complexation of tetraalkylammonium cations, mono and diprotonated amines, and amino acids with a derivatized cyclotetrachromotropylene in an aqueous solution

The derivatized cyclotetrachromotropylene host forms complexes of 1:1 host to guest stoichiometry with tetraalkylammonium cations and amino acids whereas complexes of 1:2 host to guest stoichiometry are formed with mono and diprotonated amines in an aqueous solution. Both electrostatic and hydrophobic interactions are involved in the complexation.     

苝二酸酐与嘧啶衍生物的氢键组装

Semi-empirical AM1 method was used to study 1:1 and 1:2 hydrogen bond complexes formed with perylene dianhydride and pyridine derivatives. The weak interaction energy become bigger as the number of hydrogen bonds increases. The donor groups on the host and electron-withdrawing groups on the guest molecules favor hydrogen bonding interactions, and the formation of hydrogen bonding leads to electron density flow from the host to the guest molecules. Electronic spectra of these complexes were computed using INDO/SCI method. Blue-shift of the electronic absorption spectra for the complexes, comparing that of the host,takes place, and the first peaks for different complexes changed slightly. These are in agreement with the experimental results. The cause of blue-shift was discussed, and the electronic transitions were assigned based on theoretical calculations. The potential curve of double proton transfer in the complex was calculated, and the transition state and activated energy relative to the N-H bond were obtained.     

Inclusion complexes of pantoprazole with β-cyclodextrin and cucurbit[7]uril: experimental and molecular modeling study

The inclusion complexes of the proton pump inhibitor (PPI) pantoprazole sodium (PNZ_Na) with β-cyclodextrin (βCD) and cucurbit[7]uril (CB[7]) have been investigated. Fluorescence spectroscopy and electrospray ionization mass spectrometry (ESI-MS) were used to characterize these complexes. The fluorescence intensity of PNZ_Na was remarkably enhanced by both hosts, indicating the formation of the complexes. Nevertheless, the two hosts are of comparable cavity size their effect on the fluorescence of PNZ_Na was quite different. The ESI-MS data on the other hand confirmed the formation of a 1:1 PNZ_Na: host inclusion complexes for the two hosts. We further utilized molecular dynamics to shed more light on the mechanism of complexation and on the stability of these complexes in aqueous media. The complexes were stabilized over the 20 ns of simulation time mainly via hydrogen bonding interactions in addition to hydrophobic effects and van der Waals interactions. Snapshots collected during the simulations for both complexes have clearly shown that the mode of insertion of PNZ into the two host’s cavities are different which explain the difference in fluorescence enhancement of PNZ obtained in presence of each of these hosts.     

A combined experimental and theoretical study of the molecular inclusion of organometallic sandwich complexes in a cavitand receptor

We describe herein a detailed study of the inclusion processes of several positively charged organometallic sandwich complexes inside the aromatic cavity of the self-folding octaamide cavitand 1. In all cases, the binding process produces aggregates with a simple 1:1 stoichiometry. The resulting inclusion complexes are not only thermodynamically stable, but also kinetically stable on the (1)H NMR spectroscopy timescale. The binding constants for the inclusion complexes were determined by different titration techniques. We have also investigated the kinetics of the binding process and the motion of the metallocenes included in the aromatic cavity of the host. Using DFT-based calculations, we have evaluated the energies of a diverse range of potential binding geometries for the complexes. We then computed the proton chemical shifts of the included guest in each one of the binding geometries. The agreement between the averaged computed values and the experimentally determined chemical shifts clearly supports the proposed binding geometries that we assigned to the inclusion complexes formed in solution. The combination of experimental and theoretical results has allowed us to elucidate the origins of the distinct features detected in the complexation process of the different guests, as well as their different motions inside the host.     

Micromolar Affinity and Higher: Synthetic Host–Guest Complexes with High Stabilities

The design of high-affinity synthetic host–guest complexes is of paramount importance because they are key elements in constructing unprecedented supramolecular assemblies, functional materials, molecular probes, artificial signal transduction events, and interfaces with the biological world. The present review article collects recent achievements in the design of 1 : 1 host–guest complexes with outstanding stabilities, i.e., exceeding 10⁶ M⁻¹. The relationships between the measured thermodynamic constants and the structural parameters of the interacting species are analyzed. The design features of high-affinity hosts are discussed in light of their binding properties. Different solvents and different types of noncovalent interactions are considered for the stabilization of the complexes. Finally, some hints are provided for the design of future synthetic receptors displaying high affinity and selectivity.     

Host–:Guest Properties of the Aromatic Propellene 1,4- Bis(pyrazol-1'-yl)-2,3,5,6-tetrakis(3',5'-dimethylpyrazol-1'- yl)benzene

The structures of 1,4-bis(pyrazol-1'-yl)-2,3,5,6- tetrakis(3',5'-dimethylpyrazol-1'-yl) benzene 1, its monohydrate, 1a, four 1 : 2 host : guest complexes, 1b–1e (acetic, propionic, pentanoic, and (±)-2-methyl butyric acids) and a di-picrate salt, 1f, have been determined by X-Ray analysis. In all complexes, in the salt and in the monohydrate compound, the host molecules are hydrogen bonded to two centrosymmetric related guests and to the water molecule which is disordered over two positions to mimic the inclusion complexes. In all compounds, the host exhibits Ci symmetry having the lone pair on the N(2) atom of each pyrazole pointing alternately upwards (u) and downwards (d) from the benzene ring. 1H and 13C NMR spectra of the free host 1 and of the complexes are consistent with the ududud conformation and the stoicheiometry of the inclusion compounds.     

Stability and stoichiometry of some binary fluorophore-cyclodextrin complexes

The stability and stoichiometric ratio of binary complexes among five fluorophores and β-cyclodextrin (β-CD) or heptakis-(6-amino-6-deoxy)-β-cyclodextrin (am-β-CD) were determined by means of fluorescence measurements in borate buffer at pH=8.0 and 9.0. Structure of both host and guest affected the characteristics of the binary complexes. Pyrene and anthraquinone formed a 1:2 (fluorophore: cyclodextrin) complex with both cyclodextrins. Xanthone formed 1:1 complex with β-CD and 1:2 complex with am-β-CD. A more defined behaviour was observed for crysene. In fact, both stoichiometric different complexes were detected with both hosts. Only 1:1 complexes were observed for antracene. The complex stability was affected by the pH of the solution. MM2 calculations were performed in order to gain information about the forces working on the formation of complexes.     

1H NMR spectroscopic investigation of β-cyclodextrin inclusion compounds with parecoxib

The inclusion complexes of β-CD and parecoxib [PRB] in aqueous solution were investigated using ¹H NMR spectroscopic study revealed the existence of four different equilibria for 1:1 inclusion complexes in which both the aromatic rings of the guest are tightly held by the host cavity. The NMR spectra of the PRB studied in the presence of β-CD are fully assigned and interpreted by means of COSY spectrum for the unambiguous assignment of guest aromatic ring protons. The parallel interpretation of β-CD chemical shift changes and dipolar contacts, with the aid of 2D ROESY, allows the mode of binding to be established for four possible structures of 1:1 PRB-β-CD inclusion complexes.     

A conformationally flexible, urea-based tripodal anion receptor: solid-state, solution, and theoretical studies

Tripodal tris(urea) cationic receptors 1 and 2 containing p-tolyl or octyl substituents, respectively, have been synthesized, and their association behavior with anionic guests has been studied via a variety of methods. The receptors are based around a hexasubstituted aryl core and contain both urea and pyridinium functionalities. For 1:1 complexes, anions reside within the central cavity of the host species, held by hydrogen bonds from both NH and CH donors. The following host-anion complexes have been characterized by X-ray crystallography: 1-(Br)3, 1-(PF6)3.2(CH3)2CO, and 1-(NO3)1.5(PF6)1.5. Each structure contains the receptor in a significantly different geometry, highlighting the anion-dependent conformational flexibility of 1. Solution 1H NMR spectroscopic titrations have shown the two host species to display significant affinity for both halides and hydrogen sulfate and strongly suggest the persistence of CH...X- interactions despite the presence of "stronger" NH donor groups. Variable-temperature 1H NMR studies on the more soluble octyl derivative 2 show that there is a distinct change in conformation associated with the formation of a 1:1 host/guest complex. Computations using density functional theory (with the B3LYP functional) have been employed to aid in understanding the geometry of the 1:1 host/chloride complexes of 1 and 2. These experiments suggest that the lowest energy conformation for 1-Cl is one in which the ureidopyridinium arms are orientated upward forming a cavity that is sealed by CH...pi interactions, effectively forming a unimolecular capsule, whereas for 2 a less symmetrical "2-up, 1-down" geometry is favored.     

Molecular acrobatics: self-assembly of calixarene-porphyrin cages

Calix[4]arenes equipped with two and four zinc porphyrins have been prepared, and they show remarkable flexibility in their self-assembly properties with the bidentate ligand DABCO. The calix-bisporphyrin forms a 2:2 complex with DABCO, generating a large cavity that has the potential to act as a supramolecular host. The calix-tetraporphyrin, on the other hand, forms four different complexes with DABCO depending on the stoichiometry and concentration. During the course of a titration, all four complexes are populated, leading to large conformational changes and the formation of both intramolecular and intermolecular calix-tetraporphyrin-DABCO sandwich complexes. The system was fully characterized using a combination of UV-visible and (1)H NMR spectroscopy to identify the complexes. At a calix-tetraporphyrin:DABCO ratio of 2:4, the major species is dimeric cage assembly that features a large internal cavity for guest complexation.     

Theoretical Study on the Inclusion Complex of β-Cyclodextrin and Nitrobenzene

Quantum chemical calculations were carried out to investigate the structures and properties for the inclusion complexes of nitrobenzene (NB) into β-cyclodextrin. Two low-energy conformations of β-cyclodextrin (A and B) in the gas phase were initially investigated by the PM3 and B3LYP/6-31+G(d,p) calculations, respectively. Three different orientations were considered in the inclusion process of A and B with NB to form 1:1 complexes. Potential energy scan by PM3 calculations indicated that the phenyl orientation Ab for conformation A and the equator orientation Bc for conformation B are more favorable in energy, respectively. We also considered the 2:1 inclusion complexes of host A or B with guest NB in the gas phase. PM3 calculation indicated that the host-guest interaction energies to form 1:1 complexes are more negative than those to form 2:1 NB/B complexes. Finally, we studied the solvent effect of NB/CD complex, and PM3 results show that the influence of water molecules on the inclusion process is very important. The driving forces for the inclusion process and the geometries of complexes were discussed in detail.     

Molecular photonics of polymethine dyes in complexes with cucurbit[7, 8]urils

Thiacarbo- and thiadicarbocyanine indolenine and thiazoline polymethine dyes form host?guest complexes with cucurbit[7,8]urils in water. Cucurbit[7]uril forms preferentially 1: 1 and 1: 2 monomeric complexes and cucurbit[8]uril forms 2: 1 and 2: 2 dimeric complexes. On the basis of quantum-chemical calculations, the structure of monomeric and dimeric complexes has been suggested. The complexation manifested itself in absorption, prompt and thermally activated delayed fluorescence spectra, as well as in the triplet?triplet absorption spectra. Dimeric complexes in the triplet state are involved in one-electron oxidation and participate in triplet?triplet energy transfer.     

Co‐Conformational Isomerism in a Neutral Ion‐Paired Supramolecular System

Two different counter‐ion‐free host–guest complexes have been prepared and isolated. These compounds were formed from two equally and opposite doubly‐charged species, the viologen guests 1 a ²⁺ and 1 b ²⁺ and the anti‐disulfodibenzo[24]crown‐8 [ DSDB24C8] ^2? host, which gave rise to the 1:1 neutral complexes [ 1 a?DSDB24C8 ] and [ 1 b?DSDB24C8 ]. These species are held together by hydrogen bonding and π stacking, as well as strong electrostatic interactions. The investigation of these neutral ion‐paired supramolecular systems in solution and in the solid state allowed us to establish their co‐conformational preferences. Compound [ 1 a?DSDB24C8 ], with small methyl groups as substituents on the viologen unit, may adopt three different geometries, 1) an exo nonthreaded, 2) a partially threaded, and 3) a threaded arrangement, depending on the relative spatial orientation between the host and guest: The partially‐threaded structure is preferred in solution and in the solid state. The presence of bulky tert‐butylbenzyl groups in the viologen moiety in compound [ 1 b?DSDB24C8 ] restricts the possible geometrical arrangements to one: The exo nonthreaded arrangement. This structure was confirmed in the solid state by X‐ray crystallography. The stability of the neutral complexes in solution was determined by UV/Vis spectrophotometry. The stoichiometry of the complexes was established by continuous variation experiments, and overall equilibrium constants and ΔG° values were determined on the basis of dilution experiments. The results observed are a consequence of only the intrinsic stability of the complexes as there are no additional contributions from counter ions.     

Molecular recognition. Self-assembly of molecular trigonal prisms and their host-guest adducts

Two supramolecular trigonal prisms, each bearing three molecular clefts are shown to form 1:6 and 1:7 host-guest complexes with 9-methylanthracene and one of the prisms forms a 1:2 host-guest complex with a tritopic tri-anthracene guest that registers with the recognition sites of the host.     

Encapsulation of sodium nimesulide and precursors in beta-cyclodextrin

Crystalline 1:1 inclusion complexes with beta-cyclodextrin (beta-CD) and the sodium salt of nimesulide (4-nitro-2-phenoxymethanesulfonanilide), and the sodium salt of the derivative 2-phenoxymethanesulfonanilide, have been prepared by co-precipitation from aqueous solution. The presence of true inclusion complexes was supported by elemental analysis, thermogravimetry and powder X-ray diffraction. FTIR and 13C CP MAS NMR spectroscopy confirmed that no chemical modification of the guests occurred upon formation of inclusion complexes. The reaction of the precursors 2-phenoxynitrobenzene and 2-phenoxyaniline with beta-CD was also studied and crystalline inclusion complexes with a 2:1 (host-to-guest) stoichiometry were isolated. The interaction of the different guest species with beta-CD host molecules was studied theoretically by carrying out ab initio calculations. Favourable inclusion geometries were obtained for the four guests mentioned above. On the other hand, it was found that the inclusion of the neutral guests nimesulide and 2-phenoxymethanesulfonanilide was considerably less favourable. This is in agreement with the experimentally observed difficulty in isolating true inclusion complexes containing these guests and beta-CD. The calculated lower stability is attributed to the different steric hindrance arising from the different conformational preferences of neutral and anionic forms.     

Ion-pairing molecular recognition in water: aggregation at low concentrations that is entropy-driven

Investigations into the thermodynamic parameters that characterize the binding of citrate to tris-guanidinium host 1 in water are reported. The parameters K(a), DeltaH degrees, DeltaS degrees, and DeltaG degrees for the binding event were quantified using isothermal titration calorimetry (ITC) techniques. The 1:1 binding stoichiometry was verified by a Job plot derived from NMR data, and the microcalorimetry data was collected for solutions of 1 and citrate ranging from 1 to 100 mM using phosphate buffer concentrations of 5 and 103 mM. At low buffer concentrations (low ionic strength) complexes with greater than 1:1 stoichiometries were observed by ITC, and K(1) was determined to range from 2.0 x 10(3) to 3.0 x 10(3) M(-1). At higher buffer concentrations (high ionic strength) the higher-order complexes were not detected, and K(1) was determined to be 409 M(-1). The 1:1 association of host 1 and citrate is characterized by a large favorable entropy component and negative enthalpy. However, the complexes with higher-order stoichiometry arise from desolvation processes that result from the association of polyions in aqueous media and is entirely entropy driven. This leads to an unusual observation: the dilution of one component of the host/guest complex leads to the formation of the higher-order complexes. The reason for this observation is discussed.