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Research

Department of Chemistry and Biochemistry

 

In keeping with its consistent record of achievement and high academic standards, Millsaps launched a new era in science education in 1988 with the opening of the Franklin W. Olin Hall of Science. Olin provides students and faculty with research laboratories equipped with sophisticated scientific instruments which strengthen the College's teaching and research programs in biology and chemistry.

  • Nuclear Magnetic Resonance Spectrometer
  • Atomic Absorption Spectrophotometer
  • Fourier Transform Infrared Spectrophotometer
  • Computer-based Electrophoreses Instrument
  • Inert Atmosphere Reaction Chamber
  • Gas Chromatograph - Mass Spectrometer
  • Microscale and preparative gas chromatographs
  • UV-VIS Spectrophotometer
  • Liquid Chromatograph
  • Dispersive IR Spectrophotometer

 

Faculty Research

Dr. Timothy Ward
Analytical Chemistry - Chiral Separations

Introduction

Many people may not be aware that many over the counter (OTC) as well as prescription drugs are actually marketed as two drugs called isomers. One of the most common drugs that exists as two isomers is ibuprofen, sold under the trade name advil and motrin. One isomer of this drug has a beneficial effect, and the other isomer is passed through the body. The drug thalidomide was marketed as a racemic mixture in the 1960s. One isomer of the drug has therapeutic uses, and the other isomers of the drug caused many children to have birth defects.

The atoms that are the components of molecules may have different orientations in space, and stereochemistry is the study of these different configurations. The different configurations are called stereochemical isomers. A molecule that cannot be superimposed on its mirror image is called an enantiomer, and a molecule that has two or more enantiomeric forms is referred to as being chiral. A mixture containing equal portions of the different enantiomers of a molecule is called a racemic mixture. Many drugs, pesticides, and other chemicals are sold as racemic mixtures, and the Food and Drug Administration is placing more importance on the ability to separate the constituent enantiomers of these racemic mixtures. The separation of the racemic mixtures will allow the characterizerization of the enantiomers and the determination of their physiological effects. This is extremely significant due to the fact that some enantiomers composing drugs may have no effect, and some enantiomers may actually be harmful.

Our Research

The separation of racemic mixtures into their prospective enantiomers can be quite difficult, however, due to the fact that the enantiomers have very similar physical and chemical properties. Our research group has done research using capillary electrophoresis (CE) for chiral separations. Our laboratory is equipped with a BioFocus 3000 CE system that we will use in our research. The BioFocus 3000 CE system is fully automated and is computer-controlled. Our research laboratory is also equipped with two Isco CE systems and a Shimadzu High Performance Liquid Chromatography (HPLC) system.

Macrocyclic antibiotics have proven to be useful chiral selectors that aid in chiral separations, and these molecules are used in the research carried out in our laboratory. Our research group also does investigations into the coating of the CE columns. The coating of the capillary columns is particularly important because it helps to suppress electroosmotic flow in the capillary columns making the chiral separations much more efficient.

An illustration of the chiral separation technique we use is shown below:

 

 

Dr. Wolfgang Kramer
Biochemistry - Organic Biomolecules

Oxidative Processes in DNA and other Organic Biomolecules

Oxidation of DNA has been shown to result in localization of the positive charge by formation of guanine radical cations, particularly at GG steps.  It is now accepted that reactions of these radical cations result in nicking of the DNA backbone, and thus to permanent damage.  The efficiency of these oxidations is limited due to back electron transfer.  To minimize this energy wasting step we use compounds with fragmenting bonds as oxidizing agents. Upon irradiation these compounds form a radical and a radical cation species. The radical cation species can oxidize DNA bases and becomes a stable uncharged molecule. The design and synthesis of compounds with fragmenting bonds is an integral part of our research.

We are now trying to establish quantitative relationships between one-electron oxidation and DNA damage, i.e. the number of one-electron oxidations that result in irreversible breaking of the DNA backbone.  Knowledge of the efficiency of formation of backbone breakages is important since it would allow an assessment of the other important processes that result from one-electron oxidation, and would provide information about the relative efficiencies of damage and "self-repair" mechanisms available to the DNA.

Cleavage of single-stand DNA is known to follow two main mechanisms.  One is the abstraction of a hydrogen atom from the backbone and the other is oxidation of DNA bases. By varying the oxidation potential of the radical cation we can switch the oxidative mechanism on and off.  We are planning on using photochemical steady state and time-resolved methods to quantify these different processes and their mechanisms.

Decarboxylative Photocyclization

The decarboxylative photocyclization of w-phthalimido carboxylic acids is a useful tool in the synthesis of macrocyclic ring systems.

The efficiency of this triplet reaction is probably caused by ground-state chelation effects. A large variety of heterocyclic ring system can be synthesized with the decarboxylative photocyclization. These include lactams, benzopyrrolizidines, lactones, cyclic peptides, pyrrolizidines, indolizidines and crown ethers.

Of particular interest are the [1,4]-benzodiazepines and the pyrrolo-[1,4]-benzodiazepines. This class of compounds is widely used as tranquillizers ([1,4]-benzodiazepines) as well as potential groove binder in DNA (pyrrolo-[1,4]-benzodiazepines). The photocyclization occurs with a remarkable memory of chirality effect. The configuration of the chiral center is inversed via a 1,7-triplet biradical. The reason for the this effect is probably the rigid conformation of the anthranilic acid which prevents rotation along the phthalimide-anthranilic acid axis. Control experiments with b-alanine instead of anthranilic acid show no effect of chirality transfer.

 

Dr. Jimmie Purser
Physical Inorganic - Molecular Modeling

Introduction

Molecular modeling, also known as molecular mechanics, is a method to calculate the structure and energy of molecules based on nuclear motions. Electrons are not considered explicitly, but rather it is assumed that they will find their optimum distribution once the positions of the nuclei are known. This assumption is based on the Born-Oppenheimer approximation of the Schrödinger equation.

Molecular mechanics methods are based on the following principles:

  • Nuclei and electrons are lumped into atom-like particles.
  • Atom-like particles are spherical (radii obtained from measurements or theory) and have a net charge (obtained from theory).
  • Interactions are based on springs and classical potentials.
  • Interactions must be pre-assigned to specific sets of atoms.
  • Interactions determine the spatial distribution of atom-like particles and their energies.

Our Research

Our research activities are two-fold: (1) support for departmental research projects dealing with chiral molecules; (2) exploration into environmental impact resulting from structural differences in similar molecules, environmental stereospecificity. In particular, our interests lie in how ligands impart stereospecificity in subsequent reactions that are catalyzed by the metal center in transition metal complexes.