Exploring hydrogen-bonded structures: Synthesis and X-ray crystallographic screening of a cisoid cyclic dipeptide mini-library

Understanding how and why molecular building blocks assemble into bulk structures is difficult because no unified theory for three-dimensional crystal structure prediction yet exists. Therefore, constructing a mini-library based on systematically modifying a small set of supramolecular building blocks provides an attractive approach for experimentally determining how building block geometry affects bulk structure(s). Here, rigid diamide-containing medium-sized ring systems were used to construct a solid-state hydrogen-bonded mini-library that was structurally screened via X-ray crystallography. Unlike most amides, ring-constrained amides are locked into a cisoid two-point hydrogen-bonding motif reminiscent of a DNA base pair. Three different cisoid-diamide ring systems were investigated: a six-membered diketopiperazine; a seven-membered diketobenzodiazepine; and an eight-membered diketodibenzodiazocine. Five crystal structure determinations were carried out to establish the different possible hydrogen-bonded structural motifs. Bulk structures were found to depend in a systematic way on the geometric and electronic configurations of the building blocks employed. Of more general interest is that one member of the mini-library forms an optically transparent, nanoporous, hydrogen-bonded material containing well-defined molecular channels. That material, cbetabeta in our naming scheme, is insoluble in most organic solvents but is readily soluble in strongly hydrogen-bonding solvents, and accommodates pyridine as a stoichiometric guest molecule.