Single-crystal x-ray diffraction is a powerful technique for the definitive identification of chemical structures. Although most molecules and molecular complexes can be crystallized, often enthalpic and entropic factors introduce orientational disorder that prevent determination of a high-resolution structure. Several strategies based on the inclusion of guests in a host framework that helps maintain molecular orientation have been used to overcome this challenge. However, most of these methods rely primarily on weak interactions to induce crystalline order of the included molecules.
Researchers at UC Berkeley have developed a strategy for crystallization of molecules within the pores of chiral metal-organic frameworks (MOFs) using coordinative bonding, which includes covalent and ionic bonds, and/or using chirality.
The invention can be used to determine the precise crystal structure of pharmaceutical molecules, natural products, and protein structures by diffraction techniques, such as, x-ray, neutron, and electron diffractions.
Advantages of this strategy include: (i) the molecules make covalent bonds to well-defined metal sites of the MOF; these bonds anchor them and lower their motional degrees of freedom, thereby promoting their alignment into an ordered pattern across the interior of the crystalline framework; and (ii) the absolute structure of the chiral MOF framework serves as a reference for the direct determination of the absolute configuration of bound chiral molecules. Indeed, this latter feature forgoes the reported pseudo-symmetry problems that have obscured the absolute structures that specify the enantiomorph in achiral host framework systems.