Hamilton Group Research 2003–04: Projects and Support

Work in the Hamilton laboratory is generously supported by the following organizations/programs:

The Petroleum Research Fund of the American Chemical Society

The National Science Foundation

The Camille and Henry Dreyfus Organization

Research Overview

We attempt to prepare new molecules that can express a desired property, or fulfil a prescribed function, via the establishment of non–covalent interactions with other molecules or ions. Using synthetic chemistry we prepare target systems and investigate their properties and structure with familiar physical techniques–NMR, UV and IR spectroscopies, mass spectrometry, and X–ray crystallography. Work is advancing on two broad fronts:

• Exploration of the utility of mellitic triimides as building blocks for new materials and molecular architectures

• Organic and organometallic approaches to metal–ion or small molecule binding, sensing and transport

New Molecular Building Blocks

In 2001 we reported the preparation of the first isolable mellitic triimides (see Publications No. 28): the X–ray structure of the tri–n–butyl derivative is shown. The three–fold symmetry of these systems is coupled to a capacity to accept up to three electrons, each at a distinct and well–separated potential. The framework also offers platforms for establishing non–covalent complexes via donor–acceptor interactions and hydrogen bonding with appropriate donors. Current projects include:

• Quantitation of the strength of interaction between mellitic triimides and molecular complements

• New interlocked molecular topologies from three–fold symmetric macrobicycles

• Examination of liquid crystalline characteristics, in collaboration with Prof. Lee Y. Park, Williams College.

• Redox–modulated molecular recognition, in collaboration with Prof. Vincent M. Rotello, UMass, Amherst.

Metal–Ion Binding, Sensing and Transport

Two distinct programs in molecular recognition are grouped under this general heading. One seeks to establish a rapid, and thus readily modified, synthetic entry to cation, or small molecule, binding systems that possess an integral redox active unit, in the form of a metallocene. The ultimate aim of this work is to prepare systems that may bind and/or respond (via the redox center) in a selective fashion to the presence of a guest species. The second project targets the property of transport rather the detection. In this work we seek to modify the cation binding profile of a naturally occurring ion binding antibiotic, Lasalocid.

For the former project some short, medium and long term goals have been defined:

• Establish the rapid and modifiable synthetic chemistry required for preparation of a series of cation hosts (the X–ray structure of a prototype system is shown on the right and a preliminary publication concerning this and related systems is available–see publications No. 30).

• Characterize the structures and properties of the free hosts and their cation complexes

• Prepare promising hosts for incorporation in polymeric films, or attachment to surfaces, and thus begin the process of device design

 

Our second project currently relies on traditional organic chemistry to provide simple derivatives of a natural antibiotic. The natural system forms strong, selective, complexes with sodium ions (and indeed with potassium, see X–ray structure from our work at right) but by judicious synthetic alteration of the binding pocket presented by this host we intend to encourage binding of alternative metal ions. Current work includes:

• Establishing simple organic transformations of the antibiotic that do not disturb its (relatively) sensitive structure

• Probing the conformational changes induced by these modifications, and their influence on cation binding propensity, using NMR and circular dichroism spectroscopies

• Investigating the use of chemical evolution to drive selection of the best binding conformation in new systems targeted at specific cations

• Assessing the aptitude of modified biocompatible ion binding systems as carriers for medically relevant cationic guests