Extraction of hydrophobic species into a water-soluble synthetic receptor

A deep, water-soluble cavitand extracts a variety of neutral hydrophobic species into its cavity. Flexible species such as n-alkanes tumble rapidly on the NMR time scale inside the cavity, but this motion is slowed for bulkier guests. Long, rigid guests such as p-substituted aromatics are either static or only tumble at elevated temperatures via flexing motions of the cavitand. Strong selectivity in recognition of long rigid guests is seen. The binding of neutral guests occurs via the classical hydrophobic effect; the process is entropically favored, as shown by isothermal titration calorimetry measurements. Binding affinities are generally on the order of 10(4)-10(5) M(-1). The extent of the hydrophobic stabilization is shown by the binding of long trimethylammonium salts, which bind the alkyl chain in the cavity, rather than the NMe3+ group. Dynamic NMR studies show that self-exchange of neutral guests is independent of guest concentration, and most likely occurs via rate-determining unfolding of the cavitand. In the absence of guests, the cavitand exists in a dimeric velcrand structure.     

Induced-fit molecular recognition with water-soluble cavitands

Synthesis of novel water-soluble cavitands 1 and 2 and their complexes--the caviplexes--is described. The solubility in water derives from four primary ammonium groups on the lower rim and eight secondary amide groups on the upper rim. Cavitands 1 and 2 exist as D2d velcraplex dimers in aqueous solution but the addition of lipophilic guests 15-24 induces conformational changes to the vase-like structures. The internal cavity dimensions are 8 x 10 A, and the exchange rates of guests in the caviplexes are slow on the NMR time-scale (room temperature and 600 MHz). The direct observation of bound species and the stoichiometry of the complexes is reported. The association constants (Ka) between 0.4 x 10(-1) (-deltaG295= 0.7 kcalmol(-1)) and 1.4 x 10(2)M(-1) (-deltaG295=2.9 kcalmol(-1)) in D2O and 1.4 x 10(1)(-deltaG295= 1.7 kcalmol(-1)) and 2.8 x 10(4)M(-1)(-deltaG295=6.0 kcalmol(-1)) in [D4]methanol for aliphatic guests 16-24 were determined. Guest exchange rates of the new hosts 1 and 2 are considerably slower than rates observed for typical open-ended cavities in aqueous solution.     

Influence of planarity and size on guest binding with sodium cholate aggregates

Bile salt aggregates are supramolecular structures with two types of binding sites, called primary and secondary sites. The objective of this work was to explore how the nonplanarity and size of guests (biphenyl [BP], 1-1'-binaphthyl [BNP] and dibenz[b,f]oxepin [DBX]) affected their binding affinity and dynamics to sodium cholate (NaC) aggregates. Fluorescence and laser-flash photolysis experiments were performed to obtain information on the binding environment for the guests, the accessibility of quenchers to guests in the aggregate and the dissociation rate constants of the guests from the aggregates. All guests were bound to the more hydrophobic primary aggregate, showing that this site can accommodate nonplanar molecules. However, the structure of the guest affects the structure of the primary aggregates, leading to changes in the accessibility of anions to aggregate-bound guests and to changes for the guest dissociation rate constants from the aggregates.     

Recognition of ionic guests by ionic beta-cyclodextrin derivatives

Inclusion compounds of cationic, anionic, and neutral p-substituted derivatives of tert-butylbenzene complexed in beta-cyclodextrin and its ionic 6-mono and 6-hepta derivatives were systematically investigated by isothermal titration calorimetry (ITC). All inclusion compounds showed 1:1 stoichiometry with binding constants ranging from 10 to 3 x 10(6) M(-1). The binding free energies could be subdivided into apolar and electrostatic contributions. The electrostatic interactions could be quantitatively described by Coulomb's law by taking into account the degree of protonation of hosts and guests, the orientations of the guests within the hosts, and ion shielding as described by the Debye-Hückel-Onsager theory. The orientations of the guests within the cyclodextrin cavities were determined by ROESY NMR spectroscopy.     

Guest binding and new self-assembly of bisporphyrins

In organic medium, bisprophyrins 1-6 connected by aromatic linkers self-assemble via subtle forces such as van der Waals, pi-pi stacking, and CH/pi to form supramolecular dimers. The structures of bisporphyrin dimer 1.1 were discussed using our chemical shift simulation, revealing that 1.1 mainly adopts the self-complementary structure A. ESI mass experiments of the bisporphyrins showed that 1-4 form only the dimers; however, trimers as well as the dimers of 5 and 6 were observed in the gas phase. Thus, the assemblies of bisporphyrin 5 and 6 should adopt structure B, which still has a binding site to which another bisporphyrin can fit to form oligomeric structures. The dimerization constant of bisporphyrin 1 is dependent on the solvent polarity: the values decrease in the order of toluene > chloroform > 20% methanol-chloroform. The thermodynamic studies of the dimerization processes revealed that desolvation as well as pi-pi stacking interactions play a key role in the formation of the self-complementary dimers. The binding studies of bisporphyrin 1 with a variety of electron deficient aromatic guests 9-17 were carried out in chloroform. Soret and Q-bands of 1 showed the characteristic changes with the addition of guests 9-13 and 15, and large upfield shifts of their protons were observed in their complexation studies with (1)H NMR spectroscopy. These results suggested that the electron deficient aromatic guests bound within the cleft of bisporphyrin 1 via charge transfer as well as pi-pi stacking interactions between the guests and the porphyrin rings. The dimerization constant of 1.1 is much smaller than the association constant of 1.9, suggesting that the dissociation of dimer 1.1 can be regulated by binding of 9 within the cleft. The addition of 9 into the solution of 1.1 resulted in the quick dissociation of the dimer and the formation of 1.9.     

Molecular doping of porous organic cages

Porous organic cages can act as hosts for the three-dimensional alignment of guests such as halogens and organometallics. Porous single crystals are doped by vapor sublimation to produce diamondoid arrangements of guests such as I(5)(-) and OsO(4), leading to marked conductivity enhancement in the case of I(5)(-).     

Recognition of carboxylate and dicarboxylates by azophenol–thiourea derivatives: a theoretical host–guest investigation

Geometries of azophenol–thiourea derivative complexes with acetate, oxalate, malonate, succinate, glutarate, adipate, pimelate, suberate and azelate were carried out using the integrated MO:MO method. The binding and complexation energies of these complexes were derived from the ONIOM(B3LYP/6-31G(d):AM1) calculations. The relative stabilities of the complexes of azophenol–thiourea derivatives with carboxylate guests are reported. The binding interactions of the azophenol–thiourea receptor 1, 2 and carboxylate guests are described as multipoints hydrogen bonding, where the amine and phenolic hydrogen atoms of receptors act as hydrogen bond donors in complex with acetate and all amine-hydrogen and phenolic hydrogen atoms act as hydrogen bond donors in complex with dicarboxylate guests. Thermodynamic properties of binding interactions between receptors 1, 2 and their preorganizations and complexations are also reported.     

Benzobis(imidazolium)-cucurbit[8]uril complexes for binding and sensing aromatic compounds in aqueous solution

The utilities of benzobis(imidazolium) salts (BBIs) as stable and fluorescent components of supramolecular assemblies involving the macrocyclic host, cucurbit[8]uril (CB[8]), are described. CB[8] has the unusual ability to bind tightly and selectively to two different guests in aqueous media, typically methyl viologen (MV) as the first guest, followed by an indole, naphthalene, or catechol-containing second guest. Based on similar size, shape, and charge, tetramethyl benzobis(imidazolium) (MBBI) was identified as a potential alternative to MV that would increase the repertoire of guests for cucurbit[8]uril. Isothermal titration calorimetry (ITC) studies showed that MBBI binds to CB[8] in a 1:1 ratio with an equilibrium association constant (K(a)) value of 5.7×10(5) M(-1), and that the resulting MBBI·CB[8] complex binds to a series of aromatic second guests with K(a) values ranging from 10(3) to 10(5) M(-1). These complexation phenomena were supported by mass spectrometry, which confirmed complex formation, and a series of NMR studies that showed the expected upfield perturbation of aromatic peaks and of the MBBI methyl peaks. Surprisingly, the binding behavior of MBBI is strikingly similar to that of MV, and yet MBBI offers a number of substantial advantages for many applications, including intrinsic fluorescence, high chemical stability, and broad synthetic tunability. Indeed, the intense fluorescence emission of the MBBI·CB[8] complex was quenched upon binding to the second guests, thus demonstrating the utility of MBBI as a component for optical sensing. Building on these favorable properties, the MBBI·CB[8] system was successfully applied to the sequence-selective recognition of peptides as well as the controlled disassembly of polymer aggregates in water. These results broaden the available guests for the cucurbit[n]uril family and demonstrate potentially new applications.     

Complexation of ferrocene derivatives by the cucurbit[7]uril host: a comparative study of the cucurbituril and cyclodextrin host families

The formation of inclusion complexes between cucurbit[7]uril (CB[7]) and ferrocene and its derivatives has been investigated. The X-ray crystal structure of the 1:1 inclusion complex between ferrocene and CB[7] revealed that the guest molecule resides in the host cavity with two different orientations. Inclusion of a set of five water-soluble ferrocene derivatives in CB[7] was investigated by 1H NMR spectroscopy and calorimetric and voltammetric techniques. Our data indicate that all neutral and cationic guests form highly stable inclusion complexes with CB[7], with binding constants in the 10(9)-10(10) M(-)(1) and 10(12)-10(13) M(-1) ranges, respectively. However, the anionic ferrocenecarboxylate, the only negatively charged guest among those surveyed, was not bound by CB[7] at all. These results are in sharp contrast to the known binding behavior of the same guests to beta-cyclodextrin (beta-CD), since all the guests form stable inclusion complexes with beta-CD, with binding constants in the range 10(3)-10(4) M(-1). The electrostatic surface potentials of CB[6], CB[7], and CB[8] and their size-equivalent CDs were calculated and compared. The CD portals and cavities exhibit low surface potential values, whereas the regions around the carbonyl oxygens in CBs are significantly negative, which explains the strong affinity of CBs for positively charged guests and also provides a rationalization for the rejection of anionic guests. Taken together, our data suggest that cucurbiturils may form very stable complexes. However, the host-guest interactions are very sensitive to some structural features, such as a negatively charged carboxylate group attached to the ferrocene residue, which may completely disrupt the stability of the complexes.     

Guest encapsulation and self-assembly of a cavitand-based coordination capsule

The synthesis and spectroscopic characterization of a cavitand-based coordination capsule 14 BF4 of nanometer dimensions is described. Encapsulation studies of large aromatic guests as well as aliphatic guests were performed by using 1H NMR spectroscopy in [D1]chloroform. In addition to the computational analysis of the shape and geometry of the capsule, an experimental approach to estimate the interior size of the cavity is discussed. The cavity provides a highly rigid binding space in which molecules with lengths of approximately 14 A can be selectively accommodated. The rigid cavity distinguished slight structural differences in the flexible alkyl-chain guests as well as the rigid aromatic guests. The detailed thermodynamic studies revealed that not only CH-pi interactions between the methyl groups on the guest termini and the aromatic cavity walls, but also desolvation of the inner cavity play a key role in the guest encapsulation. The cavity preferentially selected the hydrogen-bonded heterodimers of a mixture of two or three carboxylic acids 18-20. The chiral capsule encapsulated a chiral guest to show diastereoselection.     

Complexes of TETROL with selected heterocyclics: unconventional host–guest hydrogen bonding and the correlation with host selectivity

Here we investigate and compare the more salient characteristics of host–guest complexes of (+)-(2R,3R)-1,1-4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) with four heterocyclic guests, morpholine, piperidine, pyridine and dioxane. These guests each formed inclusion compounds with TETROL, and host:guest ratios were either 1:2 or 1:1. Single crystal diffraction experiments revealed unprecedented host behaviour in the presence of both piperidine and dioxane with respect to the mode of host–guest hydrogen bonding employed. Furthermore, by utilizing ¹H-NMR spectroscopy or gas chromatography (as applicable) as methods for analysing complexes obtained from competition experiments, we were able to identify the host selectivity order, and were gratified to discover that this order correlated precisely with host–guest hydrogen bond distance.     

Xanthenol clathrates: structure, thermal stability, guest exchange and kinetics of desolvation

A series of clathrates comprising the xanthenol host, 9-(4-methoxyphenyl)-9H-xanthen-9-ol, with a variety of aromatic guests displays similar structures in the space group P(-1). We have elucidated the structures of the inclusion compounds H x 1/2G, where H is 9-(4-methoxyphenyl)-9H-xanthen-9-ol and G is benzene, o-, m- and p-xylene. The structures are isostructural with respect to the host and display consistent (Host)-OH...O-(Host) hydrogen bonding. The guests lie on a centre of inversion and with the exception of the symmetrical guests, benzene and p-xylene, are disordered. An interesting case arises with m-xylene, which is ordered at low temperature (113 K) with both the host and guest molecules in general positions. At a higher temperature (283 K) the inclusion compound with m-xylene fits the series. We have correlated the structures with their thermal stabilities, guest exchange and kinetics of desolvation.     

Binding selectivity of cucurbit[7]uril: bis(pyridinium)-1,4-xylylene versus 4,4'-bipyridinium guest sites

The binding interactions between the host cucurbit[7]uril (CB7) and a series of linear guests containing bis(pyridinium)-1,4-xylylene and/or 4,4'-bipyridinium residues were investigated by (1)H NMR spectroscopy. CB7 was found to exhibit considerable binding selectivity for bis(pyridinium)-1,4-xylylene over 4,4'-bipyridinium sites. New pseudo-rotaxane and rotaxane compounds were synthesized utilizing the host-guest interactions between CB7 and the surveyed guests. [structure: see text]     

Specific molecular recognition by cage-type cyclophanes having a helically twisted and cylindrical internal cavity

Cage-type cyclophanes, which are constructed with two rigid 2,11,20-triaza[3.3.3]paracyclophane skeletons and three chiral bridging components, were prepared. Temperature-dependent ¹H NMR measurements in (CD₃)₂SO indicate that the molecular framework of the cage-type cyclophane having a cylindrical internal cavity is more rigid than those of the corresponding non-cage hosts. The guest-binding behavior of the cage-type hosts toward various guests was examined by electronic absorption spectroscopy and electrospray ionization (ESI) mass spectrometry. The present hosts were found to bind anionic guests, such as 1-hydroxy-2,4-dinitronaphthalene-7-sulfonate, 2-hydroxy-1-(phenylazo)naphthalene-6,8-disulfonate, 2,7-bis[(4-methyl-2-sulfophenyl)azo]-1,8-dihydroxynaphthalene-3,6-disulfonate, 8-anilinonaphthalene-1-sulfonate, 6-p-toluidinonaphthalene-2-sulfonate, naphthalene-1-sulfonate, and 3,5-bis(methoxycarbonyl)benzene-1-sulfonate, to form host-guest complexes. The computer-aided molecular modeling study reveals that the three pyridinium moieties bound to the chiral - and -valine residues in the bridging segments undergo chiral twist in the same directions. However, the twisted direction in the host bearing -valine residues is opposite to that evaluated for the host bearing -valine residues so that the former and latter cage-type cyclophanes furnish M and P-helical cavities, respectively, as reflected in their circular dichroism (CD) spectra. The chirality-based molecular recognition of the cage-type hosts toward enantiomeric guests such as bilirubin-IX and pamoic acid in aqueous media was investigated by CD spectroscopy.     

Blurring the Lines between Host and Guest: A Chimeric Receptor Derived from Cucurbituril and Triptycene

We report the synthesis and X‐ray crystal structure of a cucurbituril–triptycene chimeric receptor ( 1 ). Host 1 binds to guests typical of CB[6]–CB[8], but also binds to larger guests such as blue box ( 20 ) and the Fujita square ( 22 ). Intriguingly, the geometries of the 1 ? 20 and 1 ? 22 complexes blur the lines between host and guest in that both components fulfill both roles within each complex. The fluorescence output of 1 is fully quenched by the formation of complexes with pyridinium‐derived guests.     

瓜环与4,4'-二氨基二苯甲烷衍生物的相互作用

合成了三种长链多芳环多胺基客体, 它们分别由三种醛基吡啶异构体与4,4'-二氨基二苯甲烷形成的Schiff碱还原而成, 并得到¹H NMR以及质谱分析方法表征证实. 以核磁共振技术、紫外吸收光谱分析方法以及滴定¹H NMR方法为研究手段, 对瓜环(cucurbit[n]urils, n＝6～8)分别与三种4,4'-二[N-(吡啶甲基)氨基]二苯甲烷盐酸盐相互作用进行了考察. 实验结果表明, 六元瓜环与三种4,4'-二[N-(吡啶甲基)氨基]二苯甲烷盐酸盐相互作用均形成物质的量之比为2∶1的哑铃型包结配合物; 八元瓜环与三种N,N'-二(N-(吡啶甲基)二苯甲烷盐酸盐相互作用形成以类轮烷结构为主的包结配合物; 七元瓜环与三种N,N'-二(N-(吡啶甲基)二苯甲烷盐酸盐相互作用存在多种模式的竞争.     

七元瓜环与N,N′-二烷基-1,3-(4,4′-二吡啶基)丙烷衍生物的相互作用

以1,3-(4,4′-二吡啶基)丙烷为母体,合成了N,N′-二乙基\,二丁基\,二己基以及二辛基1,3-(4,4′-二吡啶基)丙烷衍生物.利用 1H NMR技术和紫外吸收光谱法,考察了Q[7]与上述链状吡啶衍生物的相互作用.实验结果表明,Q[7]与客体PC0,PC2作用,瓜环包结客体的二吡啶基丙烷部分形成1∶1的包结配合物;对于取代烷基碳链数大于4的N,N′-二烷基-1,3-(4,4′-二吡啶基)丙烷衍生物,随着主体与客体摩尔比值的增加,体系中主-客体相互作用的主导模式是Q[7]逐渐包结了客体二吡啶基丙烷部分,进而形成Q[7]包结客体两端取代烷基,甚至形成一个客体分子上"挂满"3个主体瓜环的包结物.     

Molecular-recognition properties of a water-soluble cucurbit[6]uril analogue

The molecular-recognition properties of the cucurbit[6]uril analogue (1) in aqueous buffer (sodium acetate, 50 mM, pH 4.74, 25 degrees C) toward a variety of guests including alkanediamines (6-12), aromatics (14-32), amino acids (33-36), and nucleobases (37-42) were studied by fluorescence spectroscopy. For the alkanediamines studied (H2N(CH)nNH2, n = 6, 7, 8, 9, 10, 11, 12), the association constants increase as the length of the alkane (n) is increased. Host 1 is capable of forming strong complexes with guests containing aromatic rings with association constants (Ka) ranging from 10(2) to 10(6) M(-1) as a result of the favorable pi-pi interactions that occur between host 1 and the aromatic rings of the guest when bound in the cavity of 1. Biologically relevant guests such as amino acids and nucleobases are also bound in the cavity of 1 with Ka values ranging from 10(3) to 10(6) M(-1). Consequently, cucurbit[6]uril analogue 1 functions as a versatile fluorescent sensor for the presence of a wide range of chemically and biologically important substances in aqueous solution including nitroaromatics, neurotransmitters, amino acids, and nucleobases.     

七元瓜环与N,N’-二烷基-1,3-(4,4’-二吡啶基)丙烷衍生物的相互作用

以1,3-(4,4’-二吡啶基)丙烷为母体, 合成了N,N’-二乙基、二丁基、二己基以及二辛基1,3-(4,4’-二吡啶基)丙烷衍生物. 利用1H NMR技术和紫外吸收光谱法, 考察了Q[7]与上述链状吡啶衍生物的相互作用. 实验结果表明, Q[7]与客体PC0, PC2作用, 瓜环包结客体的二吡啶基丙烷部分形成1∶1的包结配合物; 对于取代烷基碳链数大于4的N,N’-二烷基-1,3-(4,4’-二吡啶基)丙烷衍生物, 随着主体与客体摩尔比值的增加, 体系中主-客体相互作用的主导模式是Q[7]逐渐包结了客体二吡啶基丙烷部分, 进而形成Q[7]包结客体两端取代烷基, 甚至形成一个客体分子上“挂满”3个主体瓜环的包结物.     

Template effect where 1-3 molecules drive formation of a trimer carceplex

The template effect in the formation of a trimer carceplex using 1-3 molecules as templates is explored. Thirteen different templates were studied and template ratios were measured for templates of like and unlike molecularity. Five transition-state models were studied for their binding abilities to see if these mirror the template ratios. The chemical shifts of the guests and the thermodynamic and kinetic values for templation suggest that binding is key, often tight, and that the guest determining step is formation of the last covalent bond. The molecular dynamics of guests as well as the conformational dynamics of both hosts and guests further addresses nature of the recognition between host and guest. Finally, we were surprised to discover that water can bind reversibly to the trimer carceplexes, which will have ramifications to any inner phase reactions conducted inside the cage.