Publication Date

2012-06-15

Availability

Open access

Embargo Period

2012-06-15

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Chemistry (Arts and Sciences)

Date of Defense

2012-06-01

First Committee Member

Angel E. Kaifer

Second Committee Member

V. Ramamurthy

Third Committee Member

Rajeev Prabhakar

Fourth Committee Member

Lyle Isaacs

Abstract

Cucurbiturils are synthetic macrocyclic molecules prepared by condensation reactions between glycouril and formaldehyde under acidic conditions. They feature a pumpkin-like shape with two identical carbonyl-rimed portals and a hydrophobic cavity.The number of glycouril units ranging from 5 to 8 and 10 leads to varying size of the cavity, and results in their different binding properties to numerous guest molecules. Among all the members of the cucurbituril family, cucurbit[7]uril (CB7) has drawn much attention in host-guest systems due to its high level aqueous solubility (20-30 mM) in neutral H [sub]2 O. Also, it exhibits a good ability to complex a variety of guest molecules with very high binding affinities commonly between 10 [sup]7 and 10 [sup]13 M [sup]-1. A few synthetic guests have been reported to reach an exceptionally high binding affinity ca. 10 [sup]15 M [sup]-1, which is comparable to that of the avidin-biotin pair, one of the known strongest non-covalent interactions in nature. A series of cyclic ferrocene guests has been designed and synthesized, in which the two cyclopentadienyl rings are connected by a macrocyclic linker. This linker can substantially limit the free rotation around the main axis of ferrocene. The experimental results clearly show that the ferrocene group resides inside the CB7 cavity with strong binding affinities ranging from 10 [sup]8 to 10 [sup]10 M [sup]-1 , closely dependent on the size of the linker. Due to the bulky macrocyclic linker, which is mostly kept outside the CB7 in the complexes, it was concluded that the resulting complexes adopt a so-called closed conformation. The interactions between bi-armed ferrocene guests and CB7 (or CB8) are strongly affected by the properties of the side arms. We employed three bi-armed ferrocene guests with varying degree of methylation on the side arms to investigate the effects of the side arms on the association kinetics, overall binding site and stoichiometry of complexation. It has been proved that this series of guests can form inclusion complexes with CB7 symmetrically, that is, the ferrocene resides inside the CB7 cavity with each of the side arms protruding through each of the CB7 portals. However, the fully methylated guest experienced much slower association kinetics with CB7 and can also form a 2:1 complex with CB8. A simple guest host system: MFc-CB7 has been introduced to demonstrate the possibility that simple chemical transformations under relatively mild conditions could substantially decrease the binding affinity of the highly stable complex between a cationic ferrocene guest and CB7 host. Deprotonation brings down the binding affinity from 10 [sup]12 M [sup]-1 to 10 [sup]9 M [sup]-1 in terms of the association equilibrium constants, corresponding to a net loss of 14.7 kJ/mol in the stability of the complex. Further one-electron oxidation leads to another net loss of 12.4 kJ/mol in the stability of the complex with a binding affinity of 10 [sup]7 M [sup]-1. As an example, the combination of these two simple chemical procedures provides an accessible mechanism to facilitate dissociation of highly stable complexes.

Keywords

cucurbiturils; inclusion complexation; guest-host chemistry; ferrocene derivatives; high bidning affinity

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