Naturally Chiral Surfaces Could Lead to Safer Pharmaceuticals

According to a new study from Carnegie Mellon University, scalable fabrication of naturally chiral surfaces is the key to safer pharmaceuticals.

In chemistry, enantiomers refer to two molecules that are mirror images of one another. However, they are distinguishable and generally can not be superimposed onto each other. The molecules that make up the enantiomer are the chiral molecules and are important in the formation of most pharmaceutical products.

Synthesizing a "Mix" of Both

In the existing pharmaceutical production process—may it be thalidomide, penicillin, ibuprofen, and more—manufacturers are not precisely capable of isolating one chiral molecule from the other. Therefore, manufacturers end up synthesizing batches of medicines that contain both enantiomers.

On the other hand, naturally-occurring molecules responsible for life on Earth are mostly homochiral. Molecules in the DNA, as well as sugars, proteins, and amino acids, only exist in one of their two enantiomeric forms. This creates a problem in the manufacturing process of chiral pharmaceuticals—one enantiomer can cure, while its mirror image can harm.

Separation of one chiral molecule from its mirror image has required a significant investment from pharmaceutical companies. This can be achieved by creating a surface filled with one of the chiral molecules from the same enantiomer. When a batch of chiral molecules pass through it, the partner chiral molecule will bond with its mirror image, leaving the unpaired and desired molecule to pass through.

Recent breakthroughs in synthesizing drugs have allowed the creation of artificial chiral surfaces. But Carnegie Mellon University's Nisha Shukla and Andrew Gellman, both from the university's Chemical Engineering Department, have devised new methods for creating natural chiral metal surfaces.

"Until our original work, no one knew that metal surfaces could have structures that are intrinsically chiral," Gellman said in the CMU press release. He added that their discovery could lead to new processes of enantioselective chiral chemistry. This could then open new possibilities for the synthesis of enantiomerically pure drugs.

Their proposal for scalable fabrication of these intrinsically chiral surfaces includes growing "chiral metal films" to the development of chiral nanoparticles.

The Importance of Chirality in Drug Development

The news article from Carnegie Mellon University College of Engineering recounted the thalidomide incident of the 1960s. It was first known as a treatment for leprosy, then for its supposed anti-cancer properties. It was also widely popular among the very few non-barbiturate sleep-aids that can be bought over the counter.

However, by November 1961, thalidomide was taken off the shelves after being linked to children being born with teratogenic deformities, most common of which is phocomelia—underdeveloped or complete lack of limbs. These were children born from mothers who took thalidomide during their pregnancy.

The problem with the thalidomide tragedy of the 1960s lies in its chiral properties. It was marketed as a 50/50 mixture of both of its enantiomers—the left-handed molecule was medicinal while the right-handed one was highly toxic.

Another remarkable example of chiral molecules being observable in their differences is in carvone. The flavoring element often found in most essential oils have two chiral particles—one is described as smelling like spearmint, while the other like caraway.