Complexation of aliphatic ammonium ions with a water-soluble cucurbit[6]uril derivative in pure water: isothermal calorimetric, NMR, and X-ray crystallographic study.

Complexation of a water-soluble cucurbituril (CB) derivative, cyclohexanocucurbit[6]uril (CB*[6]), the cavity dimensions of which are essentially the same as those of CB[6], with various organic mono- and diammonium ions has been studied by isothermal titration calorimetry and 1H NMR spectroscopy. The binding affinity of CB*[6] with the guest molecules in water is 3-5 and 2-3 orders of magnitude higher than those of CB[6] in 50 % formic acid and in 0.05 M NaCl solution, respectively, which is mainly due to the larger enthalpic gains upon complex formation in the absence of interfering ions, such as protons and Na+. In particular, the binding constant (K) of spermine to CB*[6] was measured to be 3.4 x 10(12) M(-1), which is the highest binding constant ever reported for CB[6] or its derivatives. We also obtained the X-ray crystal structures of alpha,omega-alkanediammonium ions (C(n)DA2+, n=4-8) and spermine complexes with CB[6], in which the aliphatic chains of the guest molecules take an extended or partially bent conformation inside the CB[6] cavity, depending on the chain length. The hexamethylene chain of C6DA2+ takes a twisted conformation, which not only allows strong ion-dipole interactions between the ammonium groups and the carbonyl groups at the portals, but also increases hydrophobic interactions between the alkyl part of the guest and the inner wall of the host, which results in the largest enthalpic gain among alpha,omega-alkanediammonium ions. The thermodynamic parameters associated with the complexation are discussed in relation to the binding modes and conformations of the aliphatic chain of the guest molecules inside the host, which were investigated by 1H NMR spectroscopy and X-ray crystallography.

Supramolecular complexation of N-alkyl- and N,N'-dialkylpiperazines with cucurbit[6]uril in aqueous solution and in the solid state.

Complex stoichiometry/composition and degree of oligomerization (oligomeric supramolecular complex formation) of cucurbit[6]uril (CB[6]) with N-alkyl- and N,N'-dialkylpiperazine were investigated in aqueous solutions by means of isothermal titration calorimetry (ITC), ESI-MS, NMR and light scattering measurements. It was found that the complex stability and the degree of oligomerization increase with elongating the alkyl chain attached to the piperazine core. X-ray crystallographic studies revealed a clear correlation between the structure of CB[6]-alkylpiperazine crystals obtained from aqueous solutions and the molecular weight/properties of host-guest oligomers existed in the solution as supramolecular "seeds" of crystal formation.

Monomeric, dimeric and hexameric resorcin[4]arene assemblies with alcohols in apolar solvents.

Resorcin[4]arenes in an apolar solvent containing alcohols exist in three forms of self-assembled aggregates which have been characterised by the technique of diffusion NMR spectroscopy.

Sequence recognition and self-sorting of a dipeptide by cucurbit[6]uril and cucurbit[7]uril.

Cucurbit[7]uril forms very strong complex with zwitterionic dipeptide Phe-Gly with affinity exceeding 10(7) M(-1) and effectively recognizes peptide sequence of Phe-Gly over Gly-Phe as well as Tyr-Gly over Gly-Tyr and Trp-Gly over Gly-Trp with relative affinities of 23 000, 18 000 and 2000, respectively.

A synthetic host-guest system achieves avidin-biotin affinity by overcoming enthalpy-entropy compensation.

The molecular host cucurbit[7]uril forms an extremely stable inclusion complex with the dicationic ferrocene derivative bis(trimethylammoniomethyl)ferrocene in aqueous solution. The equilibrium association constant for this host-guest pair is 3 x 10(15) M(-1) (K(d) = 3 x 10(-16) M), equivalent to that exhibited by the avidin-biotin pair. Although purely synthetic systems with larger association constants have been reported, the present one is unique because it does not rely on polyvalency. Instead, it achieves its extreme affinity by overcoming the compensatory enthalpy-entropy relationship usually observed in supramolecular complexes. Its disproportionately low entropic cost is traced to extensive host desolvation and to the rigidity of both the host and the guest.

Chiral recognition in cucurbituril cavities.

For the first time, achiral cucurbiturils (CBs) were endowed with significant enantiomeric and distereomeric discrimination by incorporating a strong chiral binder. Calorimetric, nuclear magnetic, light-scattering, and mass spectral studies revealed that (S)-2-methylbutylamine (as a strong binder) can be discriminated by two enantiomeric supramolecular hosts, composed of CB[6] and (R)- or (S)-2-methylpiperazine, with an unprecedented 95% enantioselectivity in aqueous NaCl solution. This is the highest enantioselectivity ever reported for a supramolecular system derived from an achiral host. Similarly, CB[7], with a larger cavity, exhibited diastereoselectivities up to 8 times higher for diastereomeric dipeptides, as demonstrated for L-Phe-L-Leu-NH3+ versus L-Phe-D-Leu-NH3+.

Sequential formation of a ternary complex among dihexylammonium, cucurbit[6]uril, and cyclodextrin with positive cooperativity.

A unique ternary 1:1:1 cucurbit[6]uril (CB[6])-cyclodextrin (CD)-dihexylammonium (DHA) complex was designed and noncovalently synthesized in stepwise fashion: first, CB[6] interacts strongly with DHA to form a 1:1 complex; second, addition of CD into the solution of the 1:1 complex leads to the exclusive formation of the 1:1:1 ternary complex. The ternary complex was characterized by various experimental techniques including ITC, NMR, and ESI-MS.

Characterization of host-guest complexes of cucurbit[n]uril (n = 6, 7) by electrospray ionization mass spectrometry.

When an intramolecular cavity exists in a molecule, it can trap another chemical species to form a host-guest complex. We examine the formation of such an inclusion complex with cucurbit[n]uril (CBn, n = 6, 7) as the host to trap alkali metal or ammonium ions as the guest, by electrospray ionization mass spectrometry (ESI-MS). The results show that the inclusion complexes are formed between the three-dimensional cylinder of CBn hosts and the guest cations. Selectivity of the complex formation is dependent both on (1) ion-dipole interactions between the cylindrical portal of the CBn hosts and the guest cations and (2) the hydrophobic interactions at the inner cavity of CBn.

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.

Factors controlling the complex architecture of native and modified cyclodextrins with dipeptide (Z-Glu-Tyr) studied by microcalorimetry and NMR spectroscopy: critical effects of peripheral bis-trimethylamination and cavity size.

Complex stability constant (K), standard free energy (DeltaG degrees ), reaction enthalpy (DeltaH degrees ), and entropy change (TDeltaS degrees ) for 1:1 inclusion complexation of the diastereomeric dipeptides Z-d/l-Glu-l-Tyr (Z = benzyloxycarbonyl) and its component amino acids (Z-d/l-Glu and N-Ac-Tyr) with native alpha-, beta-, and gamma-cyclodextrins (CDs) and A,X-modified bis(6-trimethylammonio-6-deoxy)-beta-CDs (AX-TMA(2)-beta-CDs) were determined in buffer solution (pH 6.9) at T = 298.15 K by isothermal titration microcalorimetry. Concurrent NMR spectral examinations revealed that the penetration mode and the resulting complex architecture are dramatically altered by the peripheral modification and also by the CD's cavity size. Upon complexation of the ditopic Z-Glu-Tyr guest, native alpha- and beta-CDs preferentially bind the Z's phenyl group, whereas AX-TMA(2)-beta-CDs predominantly include the Tyr's phenol moiety. In contrast, native gamma-CD includes both of the aromatic moieties simultaneously in the same cavity. Furthermore, for isomeric AB-, AC, and AD-TMA(2)-beta-CDs, an inversion of enantioselectivity and a switching of the penetration mode were observed, critically depending on the position of TMA substituents.

Complexation and chiral recognition thermodynamics of gamma-cyclodextrin with N-acetyl- and N-carbobenzyloxy-dipeptides possessing two aromatic rings.

The stability constants (K) and the standard free energy (deltaG degrees ), enthalpy (deltaH degrees ), and entropy changes (deltaS degrees ) for the complexation of gamma-cyclodextrin with 34 enantiomeric and diastereomeric N-acetyl- and N-carbobenzyloxy-d/l-dipeptides with two aromatic moieties were determined in aqueous buffer solution at 298.15 K by titration microcalorimetry. Chiral recognition of the enantiomeric dipeptide pairs by gamma-cyclodextrin was found to be fairly poor, exhibiting only small percentage differences in K, while the diastereomeric dipeptides were discriminated to much greater extent with affinity differences of up to 6-7 times. The complex structures of several selected pairs were elucidated by NMR techniques. Combining the microcalorimetric and NMR data, the complexation and chiral recognition behavior of gamma-cyclodextrin is discussed in particular in terms of the length, bulkiness, and flexibility of the tether connecting the two aromatic moieties in a guest.

Solvent and guest isotope effects on complexation thermodynamics of alpha-, beta-, and 6-amino-6-deoxy-beta-cyclodextrins.

The stability constant (K), standard free energy (DeltaG degrees ), enthalpy (DeltaH degrees ), and entropy changes (TDeltaS degrees ) for the complexation of native alpha- and beta-cyclodextrins (CDs) and 6-amino-6-deoxy-beta-CD with more than 30 neutral, positively, and negatively charged guests, including seven fully or partially deuterated guests, have been determined in phosphate buffer solutions (pH/pD 6.9) of hydrogen oxide (H(2)O) or deuterium oxide (D(2)O) at 298.15 K by titration microcalorimetry. Upon complexation with these native and modified CDs, both nondeuterated and deuterated guests examined consistently exhibited higher affinities (by 5-20%) in D(2)O than in H(2)O. The quantitative affinity enhancement in D(2)O versus H(2)O directly correlates with the size and strength of the hydration shell around the charged/hydrophilic group of the guest. For that reason, negatively/positively charged guests, possessing a relatively large and strong hydration shell, afford smaller K(H2O)/K(D2O) ratios than those for neutral guests with a smaller and weaker hydration shell. Deuterated guests showed lower affinities (by 5-15%) than the relevant nondeuterated guests in both H(2)O and D(2)O, which is most likely ascribed to the lower ability of the C-D bond to produce induced dipoles and thus the reduced intracavity van der Waals interactions. The excellent enthalpy-entropy correlation obtained can be taken as evidence for the very limited conformational changes upon transfer of CD complexes from H(2)O to D(2)O.

Complexation and chiral recognition thermodynamics of 6-amino-6-deoxy-beta-cyclodextrin with anionic, cationic, and neutral chiral guests: counterbalance between van der Waals and coulombic interactions.

The stability constant (K), standard free energy (Delta G degrees), enthalpy (Delta H degrees), and entropy changes (T Delta S degrees) for the complexation of 6-amino-6-deoxy-beta-cyclodextrin with more than 50 negatively or positively charged as well as neutral guests, including 22 enantiomer pairs, have been determined in aqueous phosphate buffer (pH 6.9) at 298.15 K by titration microcalorimetry. The thermodynamic parameters obtained in this study and the relevant data for native beta-cyclodextrin indicate that the complexation and chiral discrimination behavior of the cationic host with charged guests are governed by the critical counterbalance between the electrostatic interactions of the charged groups in host and guest and the conventional intracavity interactions of the hydrophobic moiety of guest, such as hydrophobic, van der Waals, solvation/desolvation, and hydrogen-bonding interactions.