Computational Tools may Speed Up Drug Development by Years

A Virginia Tech chemist is working on computational tools that may one day speed up the drug development process by years.

T. Daniel Crawford, associate professor of chemistry, says that his research involves computations of optical rotation angles on chiral — non-superimposable — molecules.

Titled The Current State of ‘Ab Initio’ Calculations of Optical Rotation and Electronic Circular Dichcoism Spectra, the research appears as the cover article in The Journal of Physical Chemistry.

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, 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,” Crawford said.

He revealed that he used thalidomide in his study.

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 one of the two hands acted as the desired sedative, while the other hand caused significant birth defects.

Thalidomide was never approved by the FDA in the United States and was eventually taken off the market in Europe.

Crawford says that it is often vital for the chemists to determine which hand of a molecule they are using. In other words, chemists should know how to distinguish between the left and right hand of a chirac molecule.

According to him, this is where a technique called polarimetry may be helpful.

He says that 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 anti-clockwise, 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,” he said.

Crawford has revealed that 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,” he said.

His 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,” he added.

Crawford said the ultimate goal in his research was to be able to provide organic chemists with computational tools to determine the handedness of a particular molecule they are working with.

He believes that such tools may speed up the drug development process by years.

Source-ANI
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