Role of Side Chains in the Solid State Assembly of Cyclic Peptoids

Formation of stable porous frameworks based on cyclic peptoids can be triggered by strategic choice of appropriate side chains. In this contribution we demonstrate that substitution of distal propargyl side chains with methoxyethyl groups in a fully propargylated cyclic octamer peptoid (cyclo-(Npa)8 1) greatly improves the solid state stability inducing permanent one-dimensional porosity of the compound (cyclo-[(NPa)3(Nme)]2 2, Npa = N-(propargyl)­glycine, Nme = N-(methoxyethyl)­glycine). In both compounds the macrocycles align along the shortest cell axis to form tubes that are filled with guest molecules. In situ hydration and dehydration single crystal X-ray diffraction studies on compound 2 demonstrated the improved stability of the host framework. Hirshfeld surface analysis and lattice energy calculations, also supported by energy frameworks analysis, clarified the determinant packing motifs in the studied compounds explaining the improved stability in terms of architectural robustness. Methoxyethyl side chains act as H-bond acceptor by tightening as wall ties the host framework, at a difference with propargyl side chains that provide CH−π interactions with similar energy, but along a less effective direction.