Nita A. Lewis

Preparation and Study of Molecular Wires
One of the most exciting topics in modern chemistry is the possibility of creating nano-devices such as molecular computers. Already there are molecules which can operate as transistors, resistors, diodes, motors and molecular switches which may be activated by temperature, pressure or electro-magnetic radiation. Tying these devices together will require some sort of molecular wires. Many groups worldwide are working on this problem. It is necessary to prepare some sort of polymer and this usually results in making large numbers of molecules having different lengths controlled by a binomial distribution (Bell curve). Our approach allows the preparation of long wires of uniform length and in addition allows us to make wires which are bent to any desired angle. This project requires students to be skilled in both organic and inorganic synthesis. Other students are studying the properties of these wires using electronic and infrared spectroscopy, nmr and mass spectrometry techniques and electrochemistry. Several of our molecules are candidates for collaborative studies with Professor Leblanc's group in Langmuir-Blodgett techniques and scanning tunneling microscopy experiments.

Electron Transfer by Tunneling Methods
Electron transfer reactions are fundamentally important to most areas of industrial endeavors as well as to all living organisms. During the past decade, a substantial effort has been put forth to attempt to understand the complexities of this process in redox proteins where the metal center is usually buried deep within the molecule. The theoretical analysis of real proteins is a formidable task although tremendous progress has been made and new tools have been developed specifically for the quantum electronic analysis of the inhomogeneous, three-dimensional aperiodic nature of the protein structures. These tools rely heavily on the lessons learned from an analysis of the electron transfer reactions in small model compounds. Originally, it was thought that the factors that controlled the rate of electron transfer were the driving force, reorganization energy and the distance between the reacting centers. It is now generally believed that the nature of the intervening residues and their orientation relative to the donor and acceptor groups are also important both for small molecules and for proteins. In addition, it has been found that conformational change may be a controlling factor for biological electron transfer. Our approach to examining this problem was to construct simple model systems which allow us to probe in a systematic way one variable at a time affecting the electronic pathway. For example, molecules of the type shown below where R=R'=CH3, R=CH3, R'=C6H5, and R=R'=C6H5 were constructed to determine whether phenyl rings could participate in through-space electron transfer processes. We found that the two halves of the molecules chose to orient themselves with parallel phenyl/phenyl and phenyl/pyridyl rings by changing the dihedral angle of the bridging group at the expense of maximizing the space they could occupy which would require a dihedral angle of 90o. This argues for a strong inductive effect on the electronic pathway rather than a true through-space "hopping" mechanism. We are currently constructing other models which are designed to separate inductive and through-space components of the electronic pathways in an effort to address these questions.

Phenotyping Normal and Diseased Populations for P450 Isozymes
We are employing traditional probe drugs such as caffeine and dextromethorphan to determine the expression of some P450 enzymes in normal and diseased populations. Our efforts are concentrated on the comparatively little studied Hispanic and Caribbean populations as well as on the frequency of negative drug interactions occurring as a result of the lack of or over-expression of particular P450 isozymes in certain disease states. We have also begun to investigate a new harmless probe for a completely different P450 isozyme.