Macrocyclic Hosts & Adaptive Molecular Recognition

Molecular recognition in water presents a fundamental challenge in supramolecular chemistry, as the competitive hydrogen-bonding environment of aqueous media requires macrocyclic scaffolds with precisely tuned hydrophobic cavities, electrostatic complementarity, and conformational adaptability. Host molecules such as cyclodextrins, cucurbiturils, calixarenes, pillararenes, and crown ethers have emerged as versatile platforms for the selective recognition and encapsulation of guests ranging from small organic molecules and metal ions to peptides and pharmaceutical compounds under biologically relevant conditions. Recent advances in stimuli-responsive and adaptive macrocyclic systems have expanded their applications in chemical and biological sensing, drug delivery and controlled release, molecular diagnostics, selective separation, supramolecular catalysis, and functional materials. Despite substantial progress, challenges remain in achieving high selectivity, responsiveness, biocompatibility, and predictable host-guest behavior in complex aqueous and biological environments. Continued advances in molecular design, computational modeling, and mechanistic understanding are therefore essential for developing next-generation water-compatible supramolecular systems and translating molecular recognition into practical technologies and biomedical applications, including selective sensors for disease-related analytes, targeted drug-delivery systems, and responsive materials for healthcare and environmental monitoring.The aim of this Research Topic is to provide a comprehensive platform highlighting recent advances in the design, synthesis, mechanistic understanding, and applications of macrocyclic host systems operating in aqueous environments. Particular emphasis will be placed on how structural modification, cavity engineering, and dynamic supramolecular interactions influence molecular recognition, binding selectivity, and functional performance in water. The Research Topic will address key challenges associated with aqueous host-guest chemistry, including competitive solvation, weak or nonselective binding, and the complexity of biological environments. Contributions exploring responsive and adaptive macrocycles, advanced analytical and computational approaches, supramolecular catalysis, sensing, drug delivery, selective separation, and functional materials are particularly encouraged. Importantly, the Topic will highlight how fundamental advances in molecular recognition can be translated into real-world technological and biomedical applications, including molecular diagnostics, disease monitoring, controlled drug delivery, environmental sensing, and responsive materials. By bringing together fundamental and application-oriented research, this collection aims to identify emerging opportunities and guide the development of next-generation water-compatible supramolecular systems with meaningful practical impact.This Research Topic (including original research articles and reviews) welcomes contributions (including Original Research, Reviews, Mini Reviews, and Perspectives) related to:• Design and synthesis of macrocyclic host molecules, including cyclodextrins, cucurbiturils, calixarenes, pillararenes, and crown ethers• Host-guest thermodynamics and binding kinetics in aqueous media• Stimuli-responsive and adaptive supramolecular systems and assemblies• Computational and spectroscopic studies of molecular recognition• Supramolecular catalysis in water• Translational applications of molecular recognition, including healthcare, disease monitoring, environmental monitoring, and responsive technologies• Sensors and molecular imaging applications• Self-assembled, hybrid, and nanostructured functional materials• Hybrid macrocyclic and nanostructured systems• Machine learning, artificial intelligence, and predictive modeling for macrocyclic host design and host-guest recognition Topic editors: Khaleel Assaf, Ronald K. Castellano Source: https://www.frontiersin.org/research-topics/84232/macrocyclic-hosts-adaptive-molecular-recognition