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The ion-dipole effect is a force for molecular recognition and biomimetic catalysis


Stauffer, David Alan (1989) The ion-dipole effect is a force for molecular recognition and biomimetic catalysis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/DCD7-A023.


Chapter 1: In aqueous and organic media, electron-rich synthetic macrocycles serve as hosts for positively-charged guests. Binding studies in different solvents have quantified hydrophobic, donor/acceptor, and ion-dipole interactions as forces for molecular recognition. We have found clear evidence for substantial host-guest donor/acceptor π-stacking interactions (ca. 1.5 kcal/mol) in aqueous media only. The ion-dipole effect is an appreciable driving force (worth up to 3.5 kcal/mol) for molecular recognition in both aqueous and organic media. Chapter 2: Variable-temperature binding studies were performed to assess enthalpic (ΔH°) and entropic (ΔS°) contributions to free energies (ΔG°) of host-guest complexation. The van't Hoff plots (RlnK_a vs T^(-1)), which are clearly non-linear, have revealed significant values for the heat capacities (ΔC_p) of complexation in both organic and aqueous media. The ΔC_p values reflect a phenomenon generally overlooked in molecular recognition studies: both ΔH° and ΔS° are strongly temperature-dependent. Hydrophobic, donor/acceptor, and ion-dipole interactions are tentatively partitioned into ΔH° and ΔS° contributions at 298K. "Classic" hydrophobic binding is characterized by a large, positive ΔS° and a near-zero ΔH° term. Strong donor/acceptor π-stacking interactions are typically balanced between large, favorable enthalpic and unfavorable entropic contributions. The ion-dipole effect is primarily an enthalpically-driven binding force. Chapter 3: Electron-rich synthetic macrocyclic host 1 accelerates a class of alkylation reactions in aqueous media. Specifically, host 1 catalyzes the reactions of pyridine-type nucleophiles with alkyl halides in an aqueous pD~9 borate buffer. The rate constants of catalyzed versus uncatalyzed reactions and the binding affinities for substrates and products demand that host 1 binds transition states more tightly than ground states. This extension of molecular recognition through ion-dipole interactions to biomimetic catalysis provides compelling evidence for transition-state stabilization via favorable dipole-dipole interactions in aqueous media. Chapter 4: A new class of high-symmetry, water soluble, hydrophobic binding sites is described that feature 1,5-substituents on a rigid ethenoanthracene (DEA) framework. These new 1,5-hosts are compared to the analogous 2,6-hosts described in the Ph.D. theses of Petti and Shepodd. Because of more favorable solvation (by water) of amide linker groups that line the cavity, the 1,5-hosts exhibit significantly reduced affinities for all guests considered: only positively-charged guests are bound to any appreciable extent. While the binding sites designed herein are composed of topographically well-defined, rigid units to give a chiral host (with a "greater sense of twist"), the disposition of the 1,5-substituents allows the collapse of hosts into a "bowl" conformation. We therefore suggest that the more successful high-symmetry, hydrophobic binding sites are to be found with 2,6-DEA-constructed hosts rather than with 1,5-DEA-constructed hosts. One benefit of the synthetic approach taken here is the development of a series of DEA building blocks for the construction of hosts with even more pronounced hydrophobic character.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:acetylcholine binding, synthetic receptor, cation-pi interaction, molecular recognition, host-guest chemistry, biomimetic catalysis, quaternary ammonium binding, water-soluble receptor, heat capacity
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Dougherty, Dennis A.
Thesis Committee:
  • Chan, Sunney I. (chair)
  • Grubbs, Robert H.
  • Myers, Andrew G.
Defense Date:25 May 1989
Non-Caltech Author Email:davidsmdl (AT)
Record Number:CaltechTHESIS:10012010-161648037
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6091
Deposited By: Benjamin Perez
Deposited On:04 Oct 2010 14:45
Last Modified:21 Dec 2019 02:26

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