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, cββ 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.