Cyclophane Host Research Articles

Weak Hydrogen Bonding as a Basis for Concentration-Dependent Guest Selectivity by a Cyclophane Host

Crystalline inclusion complexes between the cyclophane 1 and three isomers of picoline and lutidine were grown and their properties and structures were studied by X-ray analysis, thermal gravimetry (TG), and differential scanning calorimetry (DSC). In competition experiments, the cyclophane host, which by itself is only able to form weak Cbond;H.acceptor hydrogen bonds, is able to discriminate between the different picoline or lutidine isomers, although in some cases a strong concentration dependence of the preferred isomer is observed. In the three-component experiments, inclusion of 4-picoline is strongly favored when X(4-picoline)>0.35-0.39. Very similar results were obtained in the lutidine series. The fact that 2,4-lutidine is favored when X(2,4-lutidine)>0.2 indicates that the host prefers the isomer with the methyl group in 4-position relative to the nitrogen atom. The selectivities observed can be explained based on the assignment of the inclusion complexes to different adduct classes. In the case of the picoline isomers, the preference of 4-picoline was in good agreement with the calculated lattice energies for this series. The present work also shows that caution is advisable when deducing selectivity of crystalline inclusion compounds from guest competition experiments.

A novel cyclophane–anthracene complex

A cyclophane host formed by connecting the oxygen atoms of two α,α′-di-(4-hydroxyphenyl)-1,4-diisopropylbenzene units with two pentamethylene spacers forms a unique solid-state complex with anthracene.

A New Functional Cyclophane Host. Synthesis, Complex Formation and Crystal Structures of Three Inclusion Compounds

A new macrocyclic host compound 2 having an octamethylsubstituted cyclophane structure with two intra-annular carboxylic acid functions has beensynthesized. The properties of crystalline inclusion formation are studied and X-ray crystalstructures of three inclusion complexes including acetic acid, propionic acid and acetone asthe guest molecules are reported. Inter-host channel formation with complexed guest moleculesaccommodated into the channels are typical features of the acetic acid and acetone 1 : 4 (host : guest) stoichiometric complexes being also hydrated species, while the propionicacid 1 : 2 complex is of the close packing type containing no additional water molecules.Systems of hydrogen bonds involving the host and guest functional groups are common toall structures. In the case of the acetic acid inclusion compound, a complex supramolecularhydrogen-bonded array comprising a bordering tricyclic assembly of eight molecular species exists.

Modular synthesis of pi-acceptor cyclophanes derived from 1,4,5,8-naphthalenetetracarboxylic diimide and 1,5-dinitronaphthalene.

Three neutral cyclophanes were synthesized, and their association with indole, an aromatic pi-donor, was studied. The cyclophanes were designed to contain a rigid, hydrophobic binding cavity with 1,4,5,8-naphthalenetetracarboxylic diimide or 1,5-dinitronaphthalene as the pi-acceptor. Two of the cyclophanes also contain a (S)-(valine-leucine-alanine) tripeptide unit to provide chiral hydrogen bonding interactions with guest molecules. Despite the fact that these cyclophanes contain a hydrophobic binding cavity of appropriate dimensions, their association with indole is very weak. In the case of cyclophanes derived from 1,5-dinitronaphthalene, steric interactions force the nitro groups out of the plane of the naphthalene ring, diminishing their effectiveness as pi-acceptors. A simple UV--visible titrimetric method, using N,N,N',N'-tetramethyl-1,4-phenylenediamine (TMPD) as a pi-donor, was used to rank the pi-acceptor strength of these and other aromatic units. These titrations show that 1,4,5,8-naphthalenetetracarboxylic diimide and 1,5-dinitronaphthalene derivatives are weaker pi-acceptors than viologens, which make good pi-acceptor cyclophanes. Methyl viologen is in turn a weaker pi-acceptor than anthaquinone disulfonate, suggesting that the latter may serve as a useful building block for pi-accepting cyclophane hosts.

Highly organized spherical hosts that bind organic guests in aqueous solution with micromolar affinity: microcalorimetry studies

Two novel closed-shell hemicarcerand-like hosts with spherical cavities of 11 A diameter that are soluble in aqueous solution were constructed. The binding of xylenes, aryl ethers, polyaromatic compounds, ferrocene derivatives, and bicyclic aliphatic compounds were examined by NMR spectroscopy and microcalorimetry. NMR binding studies indicated that binding depended upon guest hydrophobicity and shape. No binding was detected for guests in which a charge must be desolvated as part of inclusion or for guests that can not fit within the cavity of the host. Three complexes 2.naphthalene, 2.p-xylene, and 2.ferrocene were isolated and found to be indefinitely stable in the solid phase and in aqueous solution. The binding constants for these complexes are estimated to be greater than 10(8) M-1. Thirteen guests were examined by microcalorimetry with binding constants ranging between 10(7) and 10(3) M-1. A comparison of results obtained here with those from previous work with beta-cyclodextrin and cyclophane hosts, along with analysis of the entropy-enthalpy compensation data, indicate that there is a higher degree of guest desolvation with this host structure than with open-shell hosts. This accounts at least partially for the increase in affinity observed with these closed-shell hosts. Replacing a hydroxy group in the host portal with a hydrogen atom does not affect the binding constant, a finding consistent with the guest residing deeply buried within the host cavity. It was observed that aromatic guests are bound with higher affinity than aliphatic ones in agreement with results that point to the importance of London dispersion forces in the association of aromatic components in face-to-edge orientations. The correlation of changes in NMR chemical shift with microcalorimetry data supports a model in which increased CH-pi interactions strengthen association between host and guest due to the dominant role of van der Waals dispersion forces. Remarkably, the binding constant for the 1,4 isomer of dimethoxybenzene is 32 times higher than for the 1,2 isomer, and even greater discrimination is observed between the xylene guests since the binding constant for p-xylene is 80 times greater than that for o-xylene. This discrimination between isomeric guests by a rigid host indicates that changes in specific hydrophobic interactions have substantial effects upon binding affinity.

The electrochemically-driven decomplexation/recomplexation of inclusion adducts of ferrocene derivatives with an electron-accepting receptor

The tetracationic cyclophane, cyclobis(paraquat-4,4'-biphenylene), binds 1,1'-disubstituted ferrocene-based polyethers as a result of (i) [pi...pi] stacking between the pi-electron-deficient bipyridinium units and the pi-electron-rich cyclopentadienyl rings and (ii) [C-H...O] hydrogen bonds between the alpha-bipyridinium hydrogen atoms and the polyether oxygen atoms. However, even the presence of a bulky tetraarylmethane group--which is too large to thread through the cavity of the cyclophane host--at the end of each of the two polyether substituents of the ferrocene-containing guest does not discourage adduct formation of the inclusion type. Thus, in these adducts, the ferrocene unit of the guest is located inside the cavity of the host with its two polyether chains protruding outward from the same side of the host. The alternative pseudorotaxane geometry is not observed in solutions of these 1:1 adducts. The host-guest adducts display absorption bands in the visible spectral region, characteristic of charge-transfer interactions. In the case of one of these adducts, reversible decomplexation/recomplexation takes place upon electrochemical oxidation/reduction of the ferrocene-based unit or upon reduction/oxidation of the tetracationic cyclophane.

Binding of Acetylcholine to a Cyclophane Host. Influence of Water and Reliability of NMR Measurements of Small Association Constants

A detailed analysis of the association of acetylcho- line (ACh) and tetramethylammonium (TMA) picrates with the cyclophane tetraester 1b in CDC13 at T = 296K was undertaken to assess the reliability of measurements of small association constants by NMR shift titrations. Results showed that, with simple expedients and careful treatment of data, binding constants of 13 and 29 M-1 for ACh and TMA respectively can be measured through standard nonlinear regression procedures with ±1% accuracy. Systematic errors caused by the interfer- ence of water at low host concentration were shown to be the major source of inaccuracy. The plot of residuals of experimental data points from the regression curve was used to monitor systematic deviations while the shift of the water signal was used as a probe of processes occurring in solution.

ChemInform Abstract: Exciplex Formation in Complexes Between Cyclophane Hosts and Aromatic Guests: Evidence That the Ground‐State Complexes Exist in More than One Distinct Geometry.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Binding of Organic Cations to a Cyclophane Host As Studied with Molecular Dynamics Simulations and Free Energy Calculations

We have studied the binding of two organic cations, an iminium (IM) and a guanidinium (GU), to a cyclophane host P4--4Na+, using molecular dynamics simulations and free energy calculations. A proper treatment of the long-range electrostatic forces is essential for the stability of these highly charged complexes, and a simple cutoff at 12 A results in an artifactual dissociation of the IM−P4--4Na+ complex. Since the host is highly aromatic and the guests cationic, cation−π interactions play an important role in the complex stability. In free energy calculations, using a simple additive force field, we calculate that the relative free energy of association of IM and GU binding to the host is 2.3 kcal/mol favoring IM, which is of the correct sign but 1.4 kcal/mol too small in magnitude. Differences in van der Waals interaction energies are mainly responsible for the different binding strengths, and the host adopts different shapes when accommodating IM compared to GU. To approximately estimate the contributi...

Threading/Dethreading Exchange Rates as Structural Probes in Polypseudorotaxanes

First, the complexation of rigid bis(paraquat)-based cyclophane host 1 with linear MDI-based polyurethane guests 2−5 prepared from tetra(ethylene glycol) was studied. Through detailed analysis of 1H NMR data, we have shown a relationship between the length of the linear polyurethanes and the fraction of all threaded cyclophanes rapidly exchanging with solution upon the 1H NMR time scale. In other words, the molecular weight of the polymer can be estimated from the proportion of cyclic threaded but exchanging rapidly, i.e., those near the ends, versus those that are threaded but exchanging slowly because they do not have ready access to the ends of the macromolecule; this is essentially an end group analysis. And then in a similar study of branched polyurethanes 7−11 derived from tetra(ethylene glycol) and glycerol, it was shown that the cyclophane can be used to determine the (accessible) fraction of the polymer between a branch point and a terminus and the average length between a branch point and a terminus. Third, inclusion of bisphenol A diethoxylate units in linear polyurethanes 12−16 provides effective barriers to room-temperature threading and dethreading, allowing a “slippage” method for polyrotaxane synthesis at elevated temperature (60 or 90 °C), yielding polyrotaxanes stable for extended periods in solution at room temperature.

Binding of Acetylcholine to a Cyclophane Host. Influence of Water and Reliability of NMR Measurements of Small Association Constants

Binding of Acetylcholine to a Cyclophane Host. Influence of Water and Reliability of NMR Measurements of Small Association Constants

Exciplex Formation in Complexes between Cyclophane Hosts and Aromatic Guests: Evidence That the Ground-State Complexes Exist in More Than One Distinct Geometry

Several naphthalene derivatives and fluorene form exciplexes with cyclophane 1 when the host−guest complexes are photoexcited. The electron-rich aromatic units of host 1 act as electron donors (D), while the aromatic guests serve as electron acceptors (A). A linear dependence between exciplex fluorescence energy (hνemax) and the difference between the oxidation potential of the host and the reduction potential of the guest (EDox − EAred) has been established for the exciplexes observed with fluorene, naphthalene, and 1-fluoronaphthalene, in accord with data from previous studies in which triethylamine is the donor with these and other aromatic acceptors. Points for N-acetyl-2-naphthylalanine, 1-methylnaphthalene, 1-chloronaphthalene, and 2-chloronaphthalene deviate from the line, indicating reduced exciplex stability resulting from unfavorable steric interactions between host and guest. The guests with the highest reduction potentials, 1- and 2-cyanonaphthalene, exhibit extensive fluorescence quenching with little or no observable exciplex fluorescence, suggesting efficient formation of solvent-separated radical-ion pairs. Time-resolved fluorescence experiments reveal that the exciplexes arise via two independent pathways, one of which occurs very rapidly. The data indicate that the ground-state host−guest complexes exist at equilibrium in at least two distinct geometries.

Chiral Molecular Recognition in a Tripeptide Benzylviologen Cyclophane Host

A cationic chiral cyclophane was synthesized and studied as a host for chiral and racemic π-donor molecules. The cyclophane host has a rigid binding cavity flanked by (S)-(valine-leucine-alanine) and N,N‘-dibenzyl-4,4‘-bipyridinium subunits, which allow for hydrogen-bonding and π-stacking interactions with included aromatic guest molecules. 1H NMR binding titrations were performed with several different pharmaceutically interesting guest molecules including β-blockers, NSAIDs, and amino acids and amino acid derivatives. The host−guest complexation constants were generally small for neutral and cationic guests (0−39 M-1 at 20 °C in water/acetone mixtures). However, a (R)/(S) enantioselectivity ratio of 13 ± 5 was found for DOPA, a strongly π-donating cationic guest. Two-dimensional NOESY 1H NMR spectra confirm that (R)-DOPA binds inside the cavity of the host and that there is no measurable interaction of the cavity with (S)-DOPA under the same conditions.

Host−Guest Chemistry of a Chiral Cyclohexanediamine−Viologen Cyclophane in Solution and in the Solid State

Two π-accepting viologen substituents were coupled with the chiral barrier (1R,2R)-(+)-1,2-cyclohexanediamine to synthesize a rigid, C2-symmetric cyclophane host for aromatic guest molecules. UV−visible spectroscopic titrations show an association constant of 3.3 × 103 M-1 with indole, a hydrophobic guest, and constants in the range of 101−102 M-1 for more hydrophilic indole derivatives in water. Tryptophan methyl ester complexes this host in aqueous base with an enantioselectivity ratio of 3.3, and an association constant of 2.0 × 102 M-1 for the preferred l-enantiomer. Protonation of tryptophan methyl ester causes both the l- and d-enantiomers to have the same affinity for the host, which is, within experimental error, the same as that of the d-enantiomer in base. The cyclophane host can be intercalated into α-zirconium phosphate, a lamellar solid acid, by first swelling the latter with tetran-butylammonium hydroxide. Because the intercalated cyclophane (layer spacing = 14.7 A) has a pre-organized bindi...

CHARACTERIZATION OF THREE-DIMENSIONALLY EXTENDED HYDROPHOBIC CAVITIES. DIFFERENCE IN MOLECULAR RECOGNITION ABILITY BETWEEN STEROID AND OCTOPUS CYCLOPHANES

The guest-binding behavior of two different cyclophane hosts, each being capable of providing a three-dimensionally extended hydrophobic cavity toward aromatic guests, was examined in aqueous media: a steroid cyclophane bearing four rigid cholate moieties and an octopus cyclophane having four flexible double-chain segments. Even though the binding constant for 2,7-dihydroxynaphthalene with the steroid cyclophane was comparable to that with the octopus cyclophane, the guest binding modes were very different from each other, as confirmed by 1H NMR spectroscopy. That is, the steroid cyclophane incorporates the guest into its rigid macrocyclic cavity with axial geometry whereas the octopus cyclophane provides a three-dimensional space created by the macrocyclic skeleton and the flexible hydrocarbon chains so that the long axis of the guest becomes more or less perpendicular to the molecular axis of the host upon complexation. Temperature-dependent molecular recognition by these hosts toward 8-anilinonaphthalene-1-sulfonate was examined by means of fluorescence spectroscopy. Characteristic differences in the guest-binding mode between these hosts were sensitively reflected in the thermodynamic entropy change on host–guest complexation and the temperature-dependent microscopic viscosity experienced by the guest at the binding site. © 1997 John Wiley & Sons, Ltd.

ChemInform Abstract: Cyclophane Hosts: Binding of Polyols and Related Guests

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ChemInform Abstract: Cyclophane Hosts: Endoacidic, Endobasic, and Endolipophilic Large Cavities

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Cyclophane Hosts: Binding of Lipophilic and Cationic Guests

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Cyclophane Hosts for Quinone Guests

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of a New Cyclophane Host and Crystal Structures of Its Compounds with Neutral Guests

A new cyclophane host molecule 3 is prepared by connecting the oxygenatoms of twoα,α′-di(4-hydroxyphenyl)-1,4-diisopropylbenzene units withtwo trimethylene spacers. Solid-state structures are determined forcompounds of 3 with dichloromethane and p-xylene guests. The crystals of thetwo host-guest compounds are isomorphous.