Strong enthalpically driven complexation of neutral benzene guests in aqueous solution

Ferguson, Stephen B.; Seward, Eileen M.; Diederich, F.; Sanford, Elizabeth M.; Chou, and Iy-Chen; Inocencio-Szweda, P.; Knobler, Carolyn B.

doi:10.1021/jo00258a052

Cited by 89 publications

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“…3). The x-ray structure for 1 also indicated the presence of two disordered water molecules in the cavity (20). The structure of the hydroquinone complex in Fig.…”

Section: Structures Of the Complexesmentioning

confidence: 88%

“…Our first effort has been aimed at Diederich's octamethoxy tetraoxaparacyclophane, 1, which binds substituted benzenes in its slot-like cavity (20)(21)(22) …”

Section: Introductionmentioning

confidence: 99%

“…We have chosen to direct computational efforts at the cyclophanes in view oftheir potential structural diversity and the availability of experimental binding data for many systems. They also provide a rich venue for investigating the factors that control binding in water and the opportunity to complement the experimental studies by helping characterize the structures of the complexes, including specific interactions between host, guest, and water.Our first effort has been aimed at Diederich's octamethoxy tetraoxaparacyclophane, 1, which binds substituted benzenes in its slot-like cavity (20)(21)(22) …”

mentioning

confidence: 99%

“…Our first effort has been aimed at Diederich's octamethoxy tetraoxaparacyclophane, 1, which binds substituted benzenes in its slot-like cavity (20)(21)(22). The observed binding results for 1 and 2 reflect a complex mixture of hydrophobic association, electron donoracceptor interactions, and specific substituent hydration effects (21,22).…”

mentioning

confidence: 99%

“…The initial structure of the host was Colloquium Paper: Jorgensen and Nguyen awn taken from the crystal structure (20), standard geometries were used for the guests (26), and the p-xylene was placed in a low-energy configuration in the cavity. An extensive conformational search previously demonstrated that the lowest energy conformations of the host in a complex with p-xylene have the same conformation for the macrocycle as in the crystal structure of 1 (29,30).…”

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confidence: 99%

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Modeling the complexation of substituted benzenes by a cyclophane host in water.

Jorgensen

Nguyen

1993

Proc. Natl. Acad. Sci. U.S.A.

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Monte Carlo statistical mechanics simulations have been used to study the complexation of disubstituted benzenes by Diederich's octamethoxy tetraoxaparacyclophane host. Relative free energies of binding were obtained in water at 250C for benzene, p-xylene, p-cresol, p-dicyanobenzene, and hydroquinone from statistical perturbation theory. The computed results agree well with experimental data, including the binding affinity of benzene, which was determined after the calculations were completed. The computed structures for the complexes reveal details that are important for understanding the order of binding affinities. It is found that hydroquinone protrudes from one side of the complex and participates in hydrogen bonds between one hydroxyl group and two water molecules and in an intracomplex hydrogen bond between the other hydroxyl group and ether oxygens. The calculations also show a clear preference for binding p-cresol with the hydroxyl group hydrated rather than inside the host's cavity.The central role of intermolecular binding events in biochemistry and the potential for developing synthetic catalysts and novel materials have helped foster great experimental (1-5) and computational (6-19) interest in host-guest chemistry. The interplay between theory and experiment has been aided by the development of methodology that allows computation ofrelative and absolute free energies ofbinding (6,15,16) and by the ability of fluid simulations to provide exquisite structural details. Much computational effort has been directed at enzyme-ligand binding and the complexation of atomic ions by organic hosts (6-14), though complexes of neutral guests with organic hosts are now receiving increased attention (17-19). Water-soluble hosts that bind neutral guests are of particular interest as models of biological systems and as starting points for the design of nonenzymatic catalysts. Important contributions have been made in this area by many researchers, as reviewed by Diederich (4). The most common examples feature cyclodextrins and cyclophanes, which have relatively hydrophobic binding cylinders or slots. We have chosen to direct computational efforts at the cyclophanes in view oftheir potential structural diversity and the availability of experimental binding data for many systems. They also provide a rich venue for investigating the factors that control binding in water and the opportunity to complement the experimental studies by helping characterize the structures of the complexes, including specific interactions between host, guest, and water.Our first effort has been aimed at Diederich's octamethoxy tetraoxaparacyclophane, 1, which binds substituted benzenes in its slot-like cavity (20)(21)(22)

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“…3). The x-ray structure for 1 also indicated the presence of two disordered water molecules in the cavity (20). The structure of the hydroquinone complex in Fig.…”

Section: Structures Of the Complexesmentioning

confidence: 88%

“…Our first effort has been aimed at Diederich's octamethoxy tetraoxaparacyclophane, 1, which binds substituted benzenes in its slot-like cavity (20)(21)(22) …”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Modeling the complexation of substituted benzenes by a cyclophane host in water.

Jorgensen

Nguyen

1993

Proc. Natl. Acad. Sci. U.S.A.

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Kohlenhydraterkennung durch nichtkovalente Wechselwirkungen: eine Herausforderung für die biomimetische und die supramolekulare Chemie

1999

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Kohlenhydrate sind nicht immer so „klebrig”︁, wie man erwarten könnte. Auf molekularer Ebene sind sie wegen ihrer dreidimensionalen Komplexität sogar in organischen Lösungsmitteln schwierige Ziele für die supramolekulare Chemie; in ihrer natürlichen Umgebung (Wasser) sind sie besonders schwer faßbar und bieten daher Herausforderungen, die Chemiker künftig noch einige Zeit beschäftigen werden. Gezeigt ist der Komplex eines supramolekularen Rezeptors mit β‐D‐Glucopyranose, die sowohl über unpolare als auch polare Kontakte gebunden wird.

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Highly Organized Spherical Hosts That Bind Organic Guests in Aqueous Solution with Micromolar Affinity: Microcalorimetry Studies

Piatnitski

Flowers

Deshayes³

2000

Chem. Eur. J.

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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.

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Strong enthalpically driven complexation of neutral benzene guests in aqueous solution

Cited by 89 publications

References 0 publications

Modeling the complexation of substituted benzenes by a cyclophane host in water.

Modeling the complexation of substituted benzenes by a cyclophane host in water.

Kohlenhydraterkennung durch nichtkovalente Wechselwirkungen: eine Herausforderung für die biomimetische und die supramolekulare Chemie

Highly Organized Spherical Hosts That Bind Organic Guests in Aqueous Solution with Micromolar Affinity: Microcalorimetry Studies

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