Results promising for computational quantum chemical methods for drug development

Dec 20, 2007

New research, led by a Virginia Tech chemist, may someday help natural-products chemists decrease by years the amount of time it takes for the development of certain types of medicinal drugs. The research by T. Daniel Crawford, associate professor of chemistry, involves computations of optical rotation angles on chiral—non-superimposable—molecules. The research titled, The Current State of ‘Ab Initio’ Calculations of Optical Rotation and Electronic Circular Dichcoism Spectra, appeared recently as the cover article in The Journal of Physical Chemistry A.

Many chiral molecules are important for medical treatment for illnesses ranging from acid-reflux to cancer. The term “chiral” means that two mirror images of a molecule cannot be superimposed onto each other. In other words, some are “left-handed” and some are “right-handed.”

“Most drugs have this handedness property,” Crawford said, “and for many of these drugs, even though both hands can cause a reaction, it is a situation where one hand does a good thing and one does a bad thing.” He used thalidomide as an example. A mixture of both hands of the drug was used in the late 1950s and early 1960s to treat morning sickness in pregnant women. Later studies revealed that, while one of the two hands acted as the desired sedative, the other hand was found to cause significant birth defects. Thalidomide was never approved by the FDA in the United States and was eventually taken off the market in Europe.

For chemists, therefore, it is often vital to determine which hand of a molecule they are using. In other words, when you have a sample of a chiral molecule, how do you distinguish between the left and right hand"

This is where a technique called polarimetry comes in to play. By shooting plane-polarized light through a sample of one hand, the chiral molecule in question will rotate to a characteristic angle either clockwise or counterclockwise, and the two hands of a chiral molecule produce opposite rotations.

“So if we figure out the direction and rotation of the light or each hand, we have a frame of reference for determining whether we have the left or right hand of a molecule,” Crawford said.

The problem with this method is that synthesizing the two hands of chiral molecules is often extremely time consuming. “It can take anywhere from weeks to years,” Crawford said.

Crawford’s research applies the theory of quantum mechanics to devise computational methods in order to eliminate having to create a synthetic molecule. “The hope is that this will allow us to calculate things like optical rotation very accurately,” he said. “So when an organic chemist has a molecule and doesn’t know if it is left- or right-handed, we can calculate that directly on the computer.”

Crawford said the ultimate goal in his research is to be able to provide organic chemists with computational tools to determine the handedness of a particular molecule they are working with. He said that such tools could speed up the drug development process by years.

Source: Virginia Tech

Explore further: Team pioneers strategy for creating new materials

add to favorites email to friend print save as pdf

Related Stories

Catalytic gold nanoclusters promise rich chemical yields

Aug 25, 2014

(Phys.org) —Old thinking was that gold, while good for jewelry, was not of much use for chemists because it is relatively nonreactive. That changed a decade ago when scientists hit a rich vein of discoveries ...

Chemists uncover powerful new click chemistry reactivity

Aug 14, 2014

Chemists led by Nobel laureate K. Barry Sharpless at The Scripps Research Institute (TSRI) have used his click chemistry to uncover unprecedented, powerful reactivity for making new drugs, diagnostics, plastics, smart materials ...

Scientists fold RNA origami from a single strand

Aug 14, 2014

RNA origami is a new method for organizing molecules on the nanoscale. Using just a single strand of RNA, many complicated shapes can be fabricated by this technique. Unlike existing methods for folding DNA ...

Recommended for you

Team pioneers strategy for creating new materials

Aug 29, 2014

Making something new is never easy. Scientists constantly theorize about new materials, but when the material is manufactured it doesn't always work as expected. To create a new strategy for designing materials, ...

Plug n' Play protein crystals

Aug 29, 2014

Almost a hundred years ago in 1929 Linus Pauling presented the famous Pauling's Rules to describe the principles governing the structure of complex ionic crystals. These rules essentially describe how the ...

Protein glue shows potential for use with biomaterials

Aug 28, 2014

Researchers at the University of Milan in Italy have shown that a synthetic protein called AGMA1 has the potential to promote the adhesion of brain cells in a laboratory setting. This could prove helpful ...

User comments : 0