Pharmaceuticals – Drug Development

Since the early 1800s, scientists have recognized that some materials rotated the plane of polarized light traveling through them. By the late 1800s, it was well understood that this optical activity could be explained by looking at the chemical bonds between carbon atoms as a three dimensional structure. Mirror image (or chiral) structures of the same compound rotated light in opposite directions.

This is a well-established principal now and has become critical to the pharmaceutical sciences. Compounds that are biologically active may have very different physiological effects. One mirror image may be therapeutic while the other is harmful.

In 1996, the FDA began requiring pharmaceutical companies to get control over their synthetic processes so that the physiological impact of each of the chiral twins (or enantiomers) is separately studied and documented. In addition, it is required that the manufacturing processes for these compounds control for the excess of the desirable enantiomer and minimize the other one.

This requirement has set up whole new fields for enantiospecific synthesis, separation science for separating the enantiomers after they are formed and analyzing for the purity of the resulting products. In addition, when a new compound is created, there is a requirement for the absolute configuration of the new material to be proven.

There are many applications for the use of polarized light in these fields. Optical rotation is a method to tell how pure the chiral substance is. Circular dichroism is another method for determination of optical purity. And vibrational circular dichroism is the standard technique for proving absolute configurations of all new compounds.



CD MicroPlate Reader



Optical Rotation
Vibrational Circular Dichroism (VCD)
Circular Dichroism (CD)
High-throughput determination of enantiopurity by microplate circular dichroism, Samantha L. Pilicer, Justin M. Dragna, Adam Garland, Christopher J. Welch,, J. Org. Chem. (2020)

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