Chirality Detector Improves Drug Design and Efficacy Prospects

Researchers at the University of Central Florida (UCF) are investigating ways to enhance the development of new drugs and therapies.

A tunable plasmonic platform from UCF, which enables accurate detection of chiral molecules, could help pharmaceutical companies and biomedical labs classify enantiomers with speed and precision, leading to more efficient drug development. The platform for sensing chiral molecules is the work of a team led by professor Debashis Chanda at the UCF Nanoscience Technology Center.

Enantiomers are pairs of chiral molecules, meaning they are mirror images of each other. Each enantiomer in a pair can have different effects in the body or in chemical reactions. Some enantiomers have an efficacious effect, while others can cause toxic or severe side effects.

A recurrent challenge in drug development is to synthesize only the desired enantiomer to ensure optimal therapeutic outcomes and minimize adverse effects. Nearly 56% of all modern drugs and medicine are chiral in nature, and about 90% of these are a mixture containing equal amounts of two enantiomers of a chiral compound. The ability to accurately determine the purity of chiral molecules is therefore imperative to pharmaceutical and drug development.

The UCF-developed plasmonic technology, shown here, significantly improves the detection of the chirality of molecules, meeting a crucial demand in the fields of medical and pharmaceutical research. Courtesy of the University of Central Florida.

“In some cases, one enantiomer is the active ingredient while the other is dormant, leading to an overall reduction in the potency of the drug,” Chanda said. “As a result, the need for enantiomeric identification and purification is in crucial demand in the field of medical and pharmaceutical research.”

The UCF platform for molecular chirality detection provides the ability to fabricate a sensor and illuminate the sensor with circularly polarized light (CPL) to induce chiral light-matter interactions. The nanostructured sensor comprises an achiral, symmetric array of nanoscale, gold hole-disks, each coupled with an asymmetric optical cavity and a back reflector. The sensor is created using low-cost, high-quality, large-area nanoimprinting techniques.

A Fourier transform infrared instrument (FTIR) is used to illuminate the cavity-coupled, achiral, plasmonic metasurface of the sensor with CPL. The light-matter interaction generates superchiral light on the surface of the sensor, due to the strong coupling between the electron (plasmon) resonances on the gold array and the resonances in the optical cavity.

The superchiral light produces strong chiral near-fields on the upper surface exposed to the target analyte, allowing increased interaction with the analyte. When a chiral molecule is added on top of the sensor, it produces differential reflection between a right CPL and a left CPL, enabling the system to detect chirality.

The achiral symmetry of the plasmonic sensor suppresses the circular dichroism of the sensor itself, ensuring almost no background noise and thus allowing the detection of pure chiral signals from the molecule.

By controlling excitation conditions, scientists can achieve nearly 100% right-polarized or left-polarized chiral near-fields on the same sensor. The cavity is used to tune the chiral plasmonic resonance, allowing a wide range of chiral molecules with various absorption bands to be probed using the same nanostructure. The system permits efficient chiral light-matter interaction for the detection of vibrational molecular chirality in the mid-infrared (MIR) domain, a wavelength range that is relevant for many applications, including drug screening.

UCF NanoScience Technology Center professor Debashis Chanda shows the plasmonic platform he developed that significantly improves the detection of the chirality of molecules. Courtesy of the University of Central Florida.

In experiments, the plasmonic platform for identifying chiral molecules demonstrated a 13 orders of magnitude higher detection sensitivity for chiral enantiomers compared to conventional techniques. Moreover, the fabrication of the sensor via nanoimprinting saves costs, and a lower concentration and fewer number of molecules are needed for accurate detection compared to other methods. The tunable spectral characteristics of the achiral plasmonic system facilitate the detection of a diverse range of chiral compounds.

The robustness, ease of fabrication, and fast measurement capabilities of the system could make it a suitable platform for an on-chip, surface-enhanced, ultrasensitive chirality detection tool for the biomedical research and pharmaceutical industries. “Such a system has great potential in pharmaceutical and drug industries where high-sensitive, high-throughput, and low-cost enantiomeric purity determination is critically important,” Chanda said.

Chanda hopes the platform will be used to increase the accuracy and efficiency of future research and development. “We aim to contribute towards the development of inexpensive and fast drug identification methods for photonics and pharmaceutical research, fabrication of novel devices exhibiting superior light-matter interaction, and demonstrate a real and reliable product that is commercially viable,” he said.

The research was published in Science Advances (www.doi.org/10.1126/sciadv.adk2560).