Carbon nanodots are a type of newly engineered non-toxic nanomaterials. They have scavenging potential of free radicals, which are highly unstable and reactive molecules, in biological systems and other environments. Because free radicals are associated with inflammation, which can lead to potentially serious pathological conditions, a better understanding of the interfacial reaction mechanisms between carbon nanodots and biological systems is a critical step toward using these nanomaterials in applications. This project will enhance the understanding of the surface chemistry of carbon nanodots and the roles of the surrounding conditions on carbon nanodots interfacial reactions in biological systems. Additionally, the data on free radical life cycle from this study will help guide experiments and computational modeling in other investigations of nanomaterials for biomedical engineering applications. Broader impacts of the findings from the proposed study include: 1) Development of customized nanoscale materials for biomedical and, potentially, environmental applications, 2) Hands-on training of under-represented STEM students throughout the projects and curriculum revision that can be scaled up in other STEM oriented institutions, and 3) Impact on the K-12 science and engineering education in under-represented educational communities through the PIs network.<br/><br/>The goal of this study is to better understand how carbon nanodot's free radical scavenging potential is influenced by surrounding biological systems and biochemical conditions. The scope of the proposed work will be mainly limited to delineating the mechanisms involved in interfacial interactions. This will be done by investigating reactions between functional groups on carbon nanodots and biological/biochemical molecules. This study will be carried out by using carbon nanodots with various functional groups, polymer-protein conjugates and hybrids, and spin-trap protein radicals with three thrusts: 1) Synthesis and preparation of carbon nanodots, conjugates and hybrids, and spin-trap protein radicals, 2) Evaluation of anti-oxidative activities of the prepared molecules in biological system, and 3) Computational modeling of calorimetric techniques with empirical data. The intellectual merit of this study is to advance our understanding in the following areas: 1) Interfacial and intermolecular reaction chemistry and fundamentals of free radical reactions between nanomaterials, especially carbon nanodots and biological systems, 2) Free radical life cycle mechanisms by building computational models, which can also be applied to other similar engineered nanomaterial studies, and 3) Reaction mechanisms associated with molecules and protein radicals from immune-spin trap methods that overcome technical challenges currently present in many free radical studies.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.