Office: CHBA 121 Phone: (405) 325-2967 Email: lblank@ou.edu Fall 2007 Chem 4913 Syllabus (pdf format)

C. LeRoy Blank David Ross Boyd Professor B.S. (University of New Mexico) 1968 Ph.D. (University of Kansas) 1973 Regents' Award for Teaching, April, 1996

Division: Analytical chemistry; Toxicology Research Interests Analysis of neurochemicals, transmitters, and related enzymes,mode of action of chemical sympathectomy agents in vivo; post mortem degradation of central nervous system components; Practical applications of electroanalytical techniques; liquid chromatography in biochemical analysis; speciation of chlorine dioxide in environmental samples.

Research Description

This research program is primarily aimed at developing a better understanding of how the nervous system sends, receives, processes and handles information. A variety of novel analytical techniques are being developed to assess component levels and component interactions in the nervous system. These techniques, used in conjunction with pharmacological and/or psychological treatments, help establish specific cause-and-effect relationships. The long-term goals of this research include the understanding of emotional disorders, memory consolidation and the effects of drugs on neural processes at the molecular level. There are three major areas of current concern to this group: (1) development of more sensitive methodology for the quantitation of neurotransmitters and their related enzymes, uptake sites, and receptors, (2) elimination of rapid post mortem degradation of neurotransmitters and metabolites, and (3) synthesis and evaluation of the mode of action of highly selective neurotoxins.

The analytical procedures presently being developed primarily employ liquid chromatography with electrochemical and mass spectrometric detection. These technique can monitor as little as femtomoles to attamoles of individual compounds or enzymatic products. This allows a very rigorous dissection of the brain for quantitative determinations of pertinent species. Also employed are gas chromatography with mass spectrometry and various radiochemical procedures. Such inherently sensitive techniques are required to provide the necessary detection limits for these investigations.

One area that has caused great difficulty for neuroscientists in general is the post mortem stability of endogenous and exogenous species. While nerve cells can communicate in the millisecond time regime, the chemical alterations underlying such events may occur in the microsecond, or lower, time scales. Thus, proper sampling is crucial to the preservation of tissues for analysis in such cases. In particular, the enzymes which promote the rapid interconversion of endogenous transmitter-related species must be halted as rapidly as possible to maintain the integrity of a sample. We have recently been able to partly overcome this problem through the use of focussed microwave irradiation. We hope to extend these studies to include more transmitter systems and improvements in the microwave technique. Additionally, we are examining the post mortem metabolism associated with alcohol in an attempt to quantify levels at the time of death in, particularly, airplane accidents.

This group is also concerned with the synthesis and testing of highly selective neurotoxic species. An advanced mammalian brain, for example, may contain some trillion nerve cells. Each of these cells is interconnected with, on average, 10,000 other nerve cells, and each contains one or more of 50-100 neurochemical transmitters. The highly interwoven character of the brain thus makes correlations between specific regions and various physical/behavioral functions very difficult, indeed. Simple lesions produce massive destruction of non-target tissues. Neurochemical destroying agents, on the other hand, have shown a rather high degree of selectivity. For example, 6-hydroxydopamine can destroy up to 50 percent of norepinephrine-containing neurons without significantly altering cells containing other transmitters. But, higher doses of this agent produce simultaneous destruction of non-target neurons. We are attempting structural modifications to this and related neurotoxic compounds to attain greater selectivity with more complete destruction of the targeted neurons. We are also actively investigating the precise mode of action of this and related agents.

In summary, this program employs analytical chemistry, with a strong emphasis on chromatography and electrochemistry, to unravel problems of a neurochemical nature. We hope that such studies will eventually impact on a number of physical and mental disorders.