Deciphering Graphene-Homocysteine Interactions via Density Functional Theory: Impact on Platelet Function through an Experimental Approach

The biomedical usefulness of graphene materials depends on their stability in blood and how they interact with plasma biomolecules. In circulation, they can bind to fibrinogen, platelets, and lipids, key players in thrombosis, potentially influencing coagulation and thrombotic risk. Homocysteine (Hcy), a sulfur-containing amino acid associated with cardiovascular disorders, plays a crucial role in platelet activation and oxidative stress, yet its interaction with graphene derivatives remains poorly understood. Given the experimental complexity of systematically screening graphene derivatives for their interactions with Hcy, computational modeling and simulations offer an efficient and reliable strategy to predict binding behavior, elucidate electronic interactions, and prioritize candidates for experimental validation. Among available computational approaches, density functional theory (DFT) provides one of the most powerful models to investigate these interactions at the molecular level. In this study, we employed DFT simulations to explore the molecular interactions between Hcy and graphene derivatives, providing insights into their electronic and structural modifications. DFT results revealed that graphene oxide (GO) interacts more strongly than pristine and amine-functionalized graphene. As their interaction might influence hemostasis and thrombosis, the effect of the GO-Hcy conjugate on blood platelet functional parameters, key events of hemostasis, was explored. The GO-Hcy conjugate promoted platelet activation and aggregation. XPS and zeta-potential analyses verified successful Hcy conjugation to GO, yielding a more negative surface charge that may influence its thrombogenicity. These results underscore the importance of graphene interactions with thrombotic components and support the design of graphene-based materials with improved biocompatibility and controlled thrombogenic responses.