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

Abstract

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.

Propyne Gas Adsorption in a Cyclic Hexapeptoid: A Combined In Situ XRPD and DFTB Study**

“…In (cyclo)peptoids, CH 2 ⋅⋅⋅OC hydrogen bonds [3] take the place of ordinary NH⋅⋅⋅OC bonds in peptides. The intermolecular CH 2 ⋅⋅⋅OC interactions trigger the solid state assembly of unexpected supramolecular architectures and porous structures reported by our group [4–7] …”

“…The intermolecular CH 2 •••OC interactions trigger the solid state assembly of unexpected supramolecular architectures andp orouss tructures reported by our group. [4][5][6][7] In ar ecent contribution, we have shown how the dramatic conformational changes of compound 1 (a cyclic hexapeptoid decorated with four propargyl and two methoxyethyl side chains, Scheme 1) allow for the adsorption and releaseo fa ce-tonitrilem olecules through as ingle-crystal-to-single-crystal transformation. [4] We also demonstrated that the conformational flexibility of compound 1 leads to several solvatomorphs, as reported in Scheme 1.…”

“…The final refinement by the Rietveld method ( Figure S2 ai n the Supporting Information) included the three crystal forms 1G, 1F and 1C,o ne overall atomicd isplacementp arameter for the cyclopeptoid molecule, the profilea nd background parameters. For the propyne molecule, the overall atomic displacementparameter was fixed to 5.0, while the propyne occupancy factor was refinedt oafinal value of 0.553 (6).…”

Recent advances in crystallization and self‐assembly of polypeptoid polymers

“…Very rencently, Izzo and coworkers demonstrated that the presence of distal propargyl side chains with methoxyethyl groups can effectively enhance the stability in a fully propargylated cyclic octamer, which gave rise to permanent 1D porosity . This study demonstrated that the inter‐chain interactions are not only important for self‐assembly of linear polypeptoid, like nanosheet, but also vital for crystallization of cyclic polypeptoids.…”

The Challenge of Conformational Isomerism in Cyclic Peptoids

“…In more than ten years from the brilliant work by Kent Kirshenbaum and co‐workers, cyclic peptoids gained the status of key bioactive/biomimetic agents, efficient catalysts, promising supramolecular building‐blocks, and rigid scaffold/topological templates …”