Host–guest system of a phosphorylated macrocycle assisting structure determination of oily molecules in single-crystal form

Abstract

X-ray crystallography is the most reliable method for structure elucidation and absolute configuration determination of organic molecules based on their single-crystal forms. However, many analytes are hard to crystallize because of their low melting points (an oily state at room temperature) or conformational flexibility. Here, we report the crystallization of a macrocycle, CTX[P(O)Ph] (host), which is a cyclotrixylohydroquinoylene (CTX) derivative, with 26 oily organic molecules (guests), which is applied for the structural determination of the guest with X-ray crystallography. With the aid of the host, CTX[P(O)Ph], the guest molecules were well-ordered with full occupancy in crystal structures. In most cases, at least one guest structure without any disorder could be observed; solvent masking was not necessary for the single crystal X-ray structural analysis, and thus the structures of the guests could be successfully determined, and the absolute configuration could be assigned reliably for chiral guests with this method. The crystallization mechanism was further discussed from theoretical and experimental perspectives, suggesting that the negative electrostatic potential surface of CTX[P(O)Ph] and noncovalent interactions between the host and guest were crucial for the ordered arrangements of the guest.