The recognition afforded by macrocycle hosts in binding to a suite of different guests enables routes to rationally design materials from the molecular scale so as to empower specific and tunable functionality. In the context of their use as biomaterials and drug delivery devices, the modularity of these interactions facilitates opportunities to combine multiple bioactivities or therapeutic payloads within a single delivery platform, as well as routes to the facile incorporation of targeting motifs for functional delivery even in the complex biological milieu. A subset of macrocyclic host–guest chemistries are able to achieve affinities approaching that for biotin-avidin, offering a non-covalent approach to enable recognition in complex environments. Whereas conventional ligation reactions can be kinetically limiting, the association of host–guest motifs occurs near the diffusion limit. Accordingly, these interactions form quickly, and at high-affinities may have considerable lifetime. In this work, we describe our efforts to use supramolecular chemistry to facilitate crosslinking in three-dimensional networks of macromers and colloids. In this use, the molecular features of the specific interaction can be translated to the bulk material properties. This approach is also useful in the context of protein modification as a means of altering the stability and pharmacokinetics of therapeutics drugs. Finally, we demonstrate the use of supramolecular recognition to facilitate homing and retention of systemically administered small molecules at desired sites in the body, and in the process overcome dilution and physiologic competition to achieve site-specific accumulation. Supramolecular “click” chemistry thus affords a new tool in the suite of bioconjugation reactions to afford improved design of polymeric soft materials.

Host, guest supramolecular recognition in the design of functional soft materials

ACS Fall 2021

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