Chiral Carbon-Dot-Inspired Enantioselective Inhibition and Modulation of Hg 2+ -Induced Bovine Serum Albumin Aggregation

Protein aggregation is a hallmark feature of many neurodegenerative and nonneurodegenerative diseases. Although the mechanism of protein aggregation initiation is unknown, external risk factors such as environmental pollutants, heavy metals, pesticides, and air pollutants have been found to interact with native proteins and disturb the biological function of proteins. Mercury (Hg2+) is a common toxic pollutant in the modern industrial era, and its concentration in the environment has increased because of mining, coal combustion, industrial effluents, and municipal incineration. It can bind to different proteins, causing their misfolding and conformational changes and several types of cell damage. Most available metal chelating agents are toxic, nonspecific, and not biocompatible and can chelate and remove essential metals, which demands new therapeutic materials. Chiral carbon dots are one of these types of agents that are less toxic, and their surface can be modified easily, and the chiral property helps in the interactions with biomolecules specifically, thereby forming bionano interactions. In this study, chiral carbon dots were hydrothermally synthesized using l- and d-tartaric acid as chiral precursors, and citric acid as the source of carbon, and are abbreviated as l-TA-CDs and d-TA-CDs. The successful transfer of chirality to the carbon dots was confirmed using circular dichroism spectroscopy, and other physicochemical properties were also characterized. Here, we investigated how the enantioselectivity of chiral carbon dots interacts specifically with Hg2+-induced BSA aggregates and their subsequent aggregation-inhibitory impact. The ThT assay, along with other spectroscopic and microscopic studies, confirmed that chiral carbon dots can effectively inhibit Hg2+-induced BSA aggregation, and notably, the l-enantiomer showed more potent inhibition than the d-enantiomer, and the interaction of chiral carbon dots with Hg2+-induced aggregates is found to be spontaneous.