The Synergy of Macrocycles and Heterocycles: A Review of Coordination Behavior, Sensing, and Functional Materials Based on Calixarenes.

Heterocycle-containing calixarenes have attracted increasing attention over the past three decades owing to the unique combination of the preorganized macrocyclic framework of calixarenes with the structural and functional diversity of heterocyclic building blocks. The incorporation of heterocycles significantly expands the coordination, supramolecular, electronic, catalytic, and biological properties of these macrocycles, enabling the rational design of multifunctional molecular systems for a wide range of applications. This review provides a comprehensive overview of the synthesis, structural diversity, and applications of heterocycle-containing (thia)calixarenes reported over the last 30 years. Synthetic methodologies are critically analyzed and classified into convergent and divergent approaches, with emphasis on their advantages, limitations, and synthetic scope. Particular attention is devoted to the effects of linker type, heterocycle structure, substitution pattern, and macrocyclic conformation on the physicochemical properties and functional behavior of the resulting compounds. By integrating synthetic strategies with a systematic analysis of structure-property relationships, this review highlights how molecular design governs the performance of heterocycle-containing calixarenes across coordination, supramolecular, sensing, catalytic, and biomedical applications. Finally, current challenges and emerging research directions are discussed, providing perspectives for the rational development of advanced calixarene-based functional systems.