Function from complexity: chemical systems that achieve sensing using host-type molecules and complex equilibria

Host-based sensors that offer cross-reactivity to analytes can be valuable tools in the detection and differentiation of biologically relevant molecules. This Feature Article provides a foundational background in developing macrocylic host-based systems that harness chemical complexity to achieve sensing in biologically relevant solutions. We highlight our own contributions along with select examples from others, covering noncovalent self-assemblies, salt tolerant synthetic designs, and current multicomponent systems approaches to host-based sensing and differentation. We emphasize our personal perspective on building complex systems, as an evolving strategy to obtaining emergent information-rich outputs that surpass the performance of conventional host-based sensor pairs. These recent developments are at the frontier of the field, involving more challenging sensing tasks, including the detection and identification of highly similar analytes, biomacromolecules, and complex mixtures.