The influence of weak interactions in the backbone conformation and solid state behavior of cyclic peptoids

Cyclic peptoids are N-substituted cyclooligomeric glycines belonging to the realm of the peptidomimetic compounds. Because of the possibility to change the ring size and the side chains nature, they have proven to be an interesting building block for the formation of supramolecular structures. In particular, we reported the peculiar solid state behavior of a cyclic hexapeptoid decorated with four propargyl and two methoxyethyl side chains (1). We obtained an acetonitrile solvate crystal form and demonstrated that by heating the crystal, we could remove the guest molecules and obtain an anhydrous crystal form via a reversible single-crystal-to-single-crystal transformation. Furthermore, new pure and solvate crystal forms were obtained by modifying the crystallization solvents. We showed that it is possible to remove the guest molecules from the methanol and hydrate crystal forms and generate a permanently porous framework capable of absorbing propyne and CO2. Recently, we obtained the crystal structures of four cyclic dodecapeptoids decorated with a different combination of propargyl and methoxyethyl side chains showing a peculiar backbone conformation mimicking right- and left- handed polyproline type I helices. Using different approaches such as lattice energy calculations, Energy Frameworks analysis, and QTAIM, we wish to shed light on how weak interactions such as CH⸱⸱⸱OC hydrogen bonds, C5 hydrogen bonds, and CO⸱⸱⸱OC might influence the solid state assembly of cyclic peptoids, their solid state dynamic behavior, and their backbone conformation.