Structure–Activity Relationship of Graphene Oxide–Organic Small Molecule Composites

Graphene oxide (GO), a chemically oxidized derivative of graphene, has emerged as a versatile two-dimensional platform owing to its large surface area, hydrophilicity, and abundance of reactive oxygen-containing groups. These structural features not only enable diverse chemical modifications but also foster strong interactions with small organic molecules (SOMs), resulting in multifunctional composites with broad technological relevance. SOMs, with their structural diversity, electronic tunability, and functional group adaptability, contribute catalytic, optical, redox-active, and biological properties that complement GO’s surface chemistry. The integration of GO and SOMs is governed by distinct interaction modes, including π–π stacking, hydrogen bonding, electrostatic attraction, and covalent conjugation, each imparting unique performance advantages. This Review highlights the structure–activity relationships (SAR) that govern GO–SOM composites, emphasizing how molecular architecture influences material functionality across domains such as catalysis, sensing, environmental remediation, energy storage, and drug delivery. Representative case studies illustrate key design principles, demonstrating how specific SOM features, including aromaticity, redox activity, and hydrophilicity, dictate composite stability, selectivity, and efficacy. By establishing clear correlations between molecular-level interactions and macroscopic outcomes, this work provides a strategic framework for the rational design of GO–SOM composites. Future directions emphasize integrating environmentally improved, computational modeling and biomedical translation to accelerate the development of sustainable, high-performance hybrid nanomaterials.