Modeling the Complexation of Substituted Benzenes by a Cyclophane Host in Water

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 4; pp. 1194 - 1200
• Main Authors: Jorgensen, William L., Nguyen, Toan B.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.02.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Atomic and molecular physics; Atoms; Biochemistry; Effects of atomic and molecular interactions on electronic structure; Electronic structure of atoms, molecules and their ions: theory; Environmental and solvent effects; Ethers; Exact sciences and technology; Free energy; Hydrocarbons; Hydrogen; Hydrogen bonds; Hydroquinones; Hydroxyls; Molecules; Oxygen; Physics; Solutes; Statistics; Quaternary ammonium compound; Intermolecular interaction; Complexation; Monte Carlo method; Radial distribution function; Theoretical study; Aqueous solution; Thermodynamic properties; Organic dication; Free energy; Spiran; Organic compounds
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.4.1194

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 25⚬C 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.