News Release 97-031

April 30, 1997

This material is available primarily for archival purposes. Telephone numbers or other contact information may be out of date; please see current contact information at media contacts.

Scientists have recognized for more than a century that some molecules exist as pairs of mirror images. But, are such molecules really "righties" or "lefties", chemically speaking? New research funded by the National Science Foundation is providing an answer.

Recognizing whether a molecule's right-handed or left-handed form binds more tightly to another molecule can be critical for the design of new drugs, since one form might prove beneficial while the other could be ineffective or worse--harmful. For example, when pregnant women in the 1950s were given a 50/50 mixture of right-handed and left-handed versions of a drug called thalidomide, only one form was effective, while the other resulted in profound birth defects.

Since then, methods have been developed by drug companies to selectively synthesize or separate left-handed and right-handed molecules. However, those methods are not always cost-effective or efficient and do not allow chemists to tell beforehand which version might offer the best candidate for a future drug.

Now, an international team led by Andrew McCammon at the University of California, San Diego has used a form of computational wizardry to study a famous mirror-image molecule called bromochlorofluoromethane (CHFClBr)--a chemical used in every introductory chemistry course to illustrate "handedness" in molecules. The procedure, described in the current issue of the Journal of the American Chemical Society, could also be used to help chemists predict which mirror-image molecule might be worthwhile pursuing for drug development.

"This work is a wonderful illustration of the power that simulation and theoretical approaches, when combined with experimental approaches, can bring to solving a basic scientific question," says Kamal Shukla, program director of molecular biophysics at NSF.

It was French chemist Louis Pasteur who discovered mirror-image molecules in 1848, when he showed that a compound obtained from wine -- tartaric acid -- formed right-handed and left-handed crystals. Pasteur was able to visually identify the two different forms, and painstakingly separate them with tweezers.

The most common examples of compounds whose molecules exist in two different mirror-image forms consist of, or include, a single carbon atom bound to four different groups. That's true for simple organic molecules and for amino acids that make up key biological proteins and enzymes, which become targets for drugs. A particular biological receptor for a drug can be likened to a glove in that a left-handed drug will fit on a left-handed receptor. A right-handed drug will fit less well, if at all, into a left-handed receptor and could cause serious side effects, as was the case with thalidomide.

To find a solution to this problem, the UCSD-led researchers called upon computational techniques that permit subtle changes to be made in the shape or location of carefully chosen atoms, ultimately altering the binding strength of molecules to their targets. In drug development, such knowledge is important, since the tighter the binding, the more effective a drug is likely to be. Since the method conjured up medieval images of replacing atoms of lead with atoms of gold, it was dubbed "computational alchemy" by its originator, Andrew McCammon. Computational resources of the San Diego Partnership for Advanced Computational Infrastructure were used in the research.

-NSF-

Editors: Photos of the "leftie" and "rightie" molecules, as well as a cartoon illustration of how they work, are available by contacting Cheryl Dybas at (703) 292-7734.

---

Media Contacts
Cheryl L. Dybas, NSF, (703) 292-7734, email: cdybas@nsf.gov

Program Contacts
Kamal Shukla, NSF, (703) 292-7131, email: kshukla@nsf.gov

---

The U.S. National Science Foundation propels the nation forward by advancing fundamental research in all fields of science and engineering. NSF supports research and people by providing facilities, instruments and funding to support their ingenuity and sustain the U.S. as a global leader in research and innovation. With a fiscal year 2023 budget of $9.5 billion, NSF funds reach all 50 states through grants to nearly 2,000 colleges, universities and institutions. Each year, NSF receives more than 40,000 competitive proposals and makes about 11,000 new awards. Those awards include support for cooperative research with industry, Arctic and Antarctic research and operations, and U.S. participation in international scientific efforts.

 Get News Updates by Email 

Connect with us online
NSF website: nsf.gov
NSF News: nsf.gov/news
For News Media: nsf.gov/news/newsroom
Statistics: nsf.gov/statistics/
Awards database: nsf.gov/awardsearch/

Follow us on social
Twitter: twitter.com/NSF
Facebook: facebook.com/US.NSF
Instagram: instagram.com/nsfgov