The Structure Determination of Organic Molecules by Co-crystallization of Anthracene-Based Crystallization Chaperone

Abstract

Single crystal X-ray diffraction is considered to be a highly reliable method for determining the molecular structures and absolute conformation at the atomic level, but this technique is limited to the application of oily organic molecules that are difficult to crystallize. Here, we report an anthracene-based crystallization chaperone TMAPA to overcome the above limitation, where 56 various oily organic guest molecules were cocrystallized with TMAPA in the organic solvent. As a result, 51 high-resolution co-crystal structures of organic guest molecules (chiral or achiral) with TMAPA were determined in a short time so that 51 refined structures of oily organic guest molecules can be readily determined. Importantly, anthracene moieties introduced in the TMAPA structure could not only extend the length of arms to increase the size of pores but also adaptively adopt different conformations leading to an efficient capture of the guest molecule during the co-crystallization process. It is expected that this work will open up new possibilities for structural identification and absolute conformation determination of unknown oily organic molecules.

The atypical solubility of silver(i) pentafluorobenzoate and its use as a catch-and-release agent

“…In the absence of such functional groups, and their strong intermolecular forces directing the solid-state packing of these co-crystallisations, methodologies have instead shifted to trapping the liquid substrates within cavities or inside porous networks. 29,[32][33][34][35][36] These methodologies are impressive in the scope of their substrates successfully co-crystallised, especially for substrates that lack any readily-exploited functional groups (e.g., alkanes). 33 However, the required porosity of such networks can result in large unit cells comprised of primarily light-atom molecules (Z < Si) can act as double-edged swords, given that such systems can necessitate the use of powerful synchrotron radiation sources.…”

Benchmarking Guanidinium Organosulfonate Hydrogen-Bonded Frameworks for Structure Determination of Encapsulated Guests

“…17,19,21 Subsequently, other research groups reported the use of GS frameworks for structure determination of target molecules, 23,24 and very recently, a report in this journal described an anthracene-modified adamantoid molecular chaperone for structure determination of guests. 25 Over the past three decades, our laboratory has reported a substantial number of molecular host frameworks, built from two-dimensional hydrogen-bonded networks of guanidinium (G) and organosulfonate (S) ions (Figure 1), capable of encapsulating a wide range of guests and determining their molecular structure. 26−30 These frameworks can adopt various architectures and pucker about hydrogen-bonding "hinges" in response to the steric demands of a target guest, enabling inclusion of a wide range of guests having various sizes and shapes in stoichiometric amounts.…”

“…“molecular chaperones”, − were employed as hosts for the determination of molecular structure, including absolute configuration, for a variety of guest molecules. This method involved adding one of three different adamantoid chaperones (Figure S33) to a neat guest, in liquid form, at room temperature, heating the mixture to achieve a homogeneous solution, followed by cooling with the aim of producing a cocrystal of the adamantoid chaperone and guest. ,, Subsequently, other research groups reported the use of GS frameworks for structure determination of target molecules, , and very recently, a report in this journal described an anthracene-modified adamantoid molecular chaperone for structure determination of guests …”

“…Of the 23 guests in a head-to-head comparison, 17 were included and refined in the adamantoid molecular chaperones, whereas 22 were included and refined in the GS hosts, arguing for the use of both host systems in the arsenal of crystallization methods for structure determination of guest molecules using single crystal X-ray diffraction. Notably, except for eugenol, the two GS hosts outperform the anthracene-modified adamantoid chaperone with respect to inclusion and structure refinement for the seven guests common to both. Furthermore, the GS method is characterized by low cost, commercial availability, and facile synthesis of the organosulfonate host components, an absence of host disorder in most inclusion compounds, and manageable guest disorder when it exists.…”

“… 17 , 19 , 21 Subsequently, other research groups reported the use of GS frameworks for structure determination of target molecules, 23 , 24 and very recently, a report in this journal described an anthracene-modified adamantoid molecular chaperone for structure determination of guests. 25 …”