Hydrogen-bonded frameworks for molecular structure determination

Abstract

Single crystal X-ray diffraction is arguably the most definitive method for molecular structure determination, but the inability to grow suitable single crystals can frustrate conventional X-ray diffraction analysis. We report herein an approach to molecular structure determination that relies on a versatile toolkit of guanidinium organosulfonate hydrogen-bonded host frameworks that form crystalline inclusion compounds with target molecules in a single-step crystallization, complementing the crystalline sponge method that relies on diffusion of the target into the cages of a metal-organic framework. The peculiar properties of the host frameworks enable rapid stoichiometric inclusion of a wide range of target molecules with full occupancy, typically without disorder and accompanying solvent, affording well-refined structures. Moreover, anomalous scattering by the framework sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. An ever-expanding library of organosulfonates provides a toolkit of frameworks for capturing specific target molecules for their structure determination.

A Synthesis-Based Reverse Metabolomics Approach for the Discovery of Chemical Structures from Humans and Animals.

“…Recently, several exciting methods for structure elucidation of biological molecules have been developed, including single molecule atomic force microscopy 6 , co-crystallization of small molecules within crystalline lattices 7,8 , and CryoEM MicroED methods using crystalline powders 9 .…”

Microporosity of a Guanidinium Organodisulfonate Hydrogen‐Bonded Framework

“…that enable accommodation of differently sized, shaped, and functionalized compounds as guests. In this manner, GS inclusion compounds have been used for small‐molecule separations, pheromone or luminophore binding, structural analysis of target guests, the design of nonlinear optical materials, the confinement of reactive species, chiral discrimination, etc …”

An Ultrastable π–π Stacked Porous Organic Molecular Framework as a Crystalline Sponge for Rapid Molecular Structure Determination

“…However, many organic molecules tend to form oils or amorphous phases, or be frustrated to grow proper-sized single crystals with good crystallographic quality for X-ray diffraction analysis. In order to get suitable crystals for analysis, Richert and his co-workers have used "adamantane crystallization chaperone" strategy to solve the crystallization problem of small molecules, 1 Ward and colleagues employed similar tactics that relying on single-step co-crystallization of guest molecules within guanidinium organosulfonate hydrogen-bonded frameworks, 2 while others have tried to make crystals growing easier by using polyelectrolyte solutions and shear flow, 3 or employing the "encapsulated nanodroplet crystallization methodology" with smearing silicone oil upon the solution of analyte. 4 Instead, Fujita and colleagues took a different tact to put forward an innovative protocol "crystalline sponge method", in which the analytes do not require to grow single crystals.…”