A UMR chemistry professor’s development of a process to sort biologically potent, useful chemicals from their less useful and sometimes toxic counterparts is listed as one of the most important advances in chemistry in 2003 by Chemical and Engineering News, the magazine of the American Chemical Society.
The process was developed by Dr. Jay A. Switzer, the Donald L. Castleman/Foundation for Chemical Research Professor of Discovery at UMR, and his colleagues in UMR’s Graduate Center for Materials Research. The team described their work in a paper published in the Oct. 2 issue of the British journal Nature.
Chemical and Engineering News highlights the work in its annual "year in review" section of the Dec. 22 edition. An image from the team’s work is featured on the cover of the Dec. 22 issue.
Switzer and his colleagues developed a process to separate or detect chiral molecules — or "handed," mirror-image molecules — using electrodeposited chiral surfaces. This method for detecting the molecules had never been done before. Normally, chemists use a process that requires a homogeneous catalyst or an enzyme solution. Switzer’s process is simpler and less expensive.
In the short term, the process could simplify the production of such drugs as ibuprofen, Paxil and Nexium. In the long term, Switzer envisions the development of chiral sensors that could be implanted in the human body to monitor drug levels; or outside the body to detect chemical warfare agents.
"Throughout the biological world, in all living things, there are molecules which have a right- and a left-hand form," Switzer says. The two forms are like a person’s right and left hands — almost identical, only reversed. "They are mirror images, but they aren’t superimposable," Switzer explains. "That is what we mean by chiral."
In the process of synthesizing molecules by normal chemical reactions, both the right- and left-hand forms of the molecules tend to be produced. But just as humans have a right- or left-handed preference, one form of the molecule tends to be very active and the other tends to be at best not very active; at worst, toxic.
One example of this is the drug thalidomide, originally used as a sedative. In the 1950s in Europe, thalidomide was prescribed to pregnant women to aid morning sickness. However, while one "hand" of the molecule relieved the woman’s nausea, the other hand was toxic, and caused birth defects.
Another common pharmaceutical example of chirality is the drug ibuprofen, commonly found in over-the-counter pain relievers. In its case, the molecule’s left hand is 100 times more powerful than the right. Switzer estimates that approximately one third of all drugs are chiral, including such familiar brands as Lipitor, Zocor, Paxil, Zoloft and Nexium each of which yield sales of more than $1 billion a year.
Switzer and his colleagues are continuing this work in UMR’s Graduate Center for Materials Research. Working with Switzer on the chiral surfaces research are Hiten M. Kothari, a graduate student who received a master’s degree in chemical engineering from UMR in 2002; Dr. Philippe Poizot, a former post-doctoral fellow at UMR; Dr. Shuji Nakanishi, a post-doctoral fellow from Osaka University; and Dr. Eric W. Bohannan, an X-ray diffraction specialist at UMR’s Graduate Center for Materials Research. Bohannan received a Ph.D. in chemistry at UMR, where he first worked with Switzer.