HKBU Scientists Develop Technique to Eliminate Drug Side Effects

Tuesday, May 26, 2020 - 10:58

Scientists from Hong Kong Baptist University (HKBU) have developed a novel technique that can produce pure therapeutic drugs without the associated side effects.

The approach, which uses a nanostructure fabrication device, can manipulate the chirality of drug molecules by controlling the direction a substrate is rotated within the device, thus eliminating the possible side effects that can arise when people take drugs containing molecules with the incorrect chirality, SciTech Daily reports.

Published in the renowned international scientific journal Nature Chemistry, the research findings pave the way towards the mass production of purer, cheaper, and safer drugs that can be made in a scalable and more environmentally-friendly way.

Many chemical molecules have two configurations, or chiral versions, that are mirror images of each other. While sharing the same molecular formula, the two chiral versions have different arrangements of their constituent atoms in space. The two versions of the molecules are characterized by left-handed and right-handed chiral configurations like human hands. Molecules with “left-handed” and “right-handed” chirality can have totally different biochemical effects.

More than half of the therapeutic drugs are made up of equal amounts of left-handed and right-handed chiral molecules, commonly known as “racemates”; one can cure specific diseases, but the other may have adverse effects. Separating and producing molecules with only the chiral arrangement (known as a single enantiomer) responsible for the therapeutic effects can help to produce drugs with improved safety and efficacy.

Dr. Jeffery Huang Zhifeng, Associate Professor in the Department of Physics at HKBU, and his research team devised a novel approach to manipulating molecular chirality through macro-scale control in collaboration with Sichuan University, Guangxi Medical University and the Southern University of Science and Technology. It involves mediating the manipulation with helical metal nanostructures (i.e. metal nanohelices) that are in the shape of a helical spring, and they have a characteristic size of one-thousandth of the diameter of a human hair.

The research team fabricated the metal nanohelices using a nanofabrication technique called glancing angle deposition (GLAD). Silver and copper were deposited onto a supporting substrate that was rotated clockwise and counterclockwise to fabricate the right-handed and left-handed metal nanohelices, respectively.

The research team then used ultraviolet light to induce a chemical reaction. This caused 2-anthracenecarboxylic acid (AC) molecules adsorbing on the metal nanohelices to undergo the chemical reaction and form chiral molecular products, which are similar to some chiral drugs.

When AC was attached to the surface of the right-handed metal nanohelices and exposed to ultraviolet light, it preferentially produced “right-handed” chiral molecular products. By the same token, when AC was adsorbed on the surface of the left-handed metal nanohelices and exposed to ultraviolet light, it preferentially produced “left-handed” chiral molecular products. In other words, the chirality of the molecular product can be reliably determined by the chirality of the metal nanohelices, which is controlled by the direction of substrate rotation.

“Our success in manipulating molecular chirality through macroscopic engineering allows the convenient synthesis of drugs in single-enantiomer forms with only left- or right-handedness. Hence, it will help get rid of the adverse, sometimes fatal, side effects of many therapeutic drugs,” said Dr. Huang.

Reference: “Enantioselective photoinduced cyclodimerization of a prochiral anthracene derivative adsorbed on helical metal nanostructures” by Xueqin Wei, Junjun Liu, Guang-Jie Xia, Junhong Deng, Peng Sun, Jason J. Chruma, Wanhua Wu, Cheng Yang, Yang-Gang Wang and Zhifeng Huang, 20 April 2020, Nature Chemistry.

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