The Crystalline Sponge Method in Water

Abstract

The crystalline sponge method entails the elucidation of the (absolute) structure of molecules from a solution phase using single‐crystal X‐ray diffraction and eliminates the need for crystals of the target compound. An important limitation for the application of the crystalline sponge method is the instability of the available crystalline sponges that can act as host crystals. The host crystal that is most often used decomposes in protic or nucleophilic solvents, or when guest molecules with Lewis basic substituents are introduced. Here a new class of (water) stable host crystals based on f‐block metals is disclosed. It can be shown that these hosts not only increase the scope of the crystalline sponge method to a wider array of solvents and guests, but that they can even be applied to aqueous solutions containing hydrophilic guest molecules, thereby extending the crystalline sponge method to the important field of water‐based chemistry.

Guest-protein incorporation into solvent channels of a protein host crystal (hostal)

“…Sponge systems exploit the small channels of crystalline hosts to accommodate, and optimally to order, small guests, although the fundamental principles of host-guest interactions for the sponge method are not fully understood (Hayes et al, 2016). Recent developments with crystal sponge hosts have allowed the structure determination of a wider range of guests including increasingly larger, more flexible and chemically complex molecules (Yoshioka et al, 2015;Ning et al, 2016;Rosenberger et al, 2020) as well as compounds in aqueous solution (Poel et al, 2019). Commonly used host-guest sponge systems are typically not designed for interactions with a specific guest, and a single crystal host may be used for guests with varying host-guest interactions (Hoshino et al, 2016).…”

“…In this socalled crystal sponge method, guest molecules are incorporated via diffusion into the solvent channels of an existing host crystal, often a metal-organic framework, although metal-free porous crystals have also been used (Inokuma et al, 2013;Sanna et al, 2015;Hoshino et al, 2016). Optimization of this method (Hoshino et al, 2016) has allowed the structure determination of difficult cases, including guest compounds with axial or planar chirality (Yoshioka et al, 2015), small flexible compounds (Ning et al, 2016) and modified metabolites (Rosenberger et al, 2020) or other guest compounds in aqueous solution (Poel et al, 2019). The narrow solvent channels of most organic and metal-organic frameworks limit this technique to small-molecule guests.…”

Applying the Crystalline Sponge Method to Agrochemicals: Obtaining X-ray Structures of the Fungicide Metalaxyl-M and Herbicide S-Metolachlor

“…This helps guest inclusion by allowing a greater quantity of the target compound to enter the MOF pores and reduces the chance of guest molecules occupying the same sites as solvent molecules, which could increase the difficulty of guest structure refinement. 31 …”

“… 38 Another example is the encapsulation of 99% pure (−)-carvone into the host framework RUM-2. 31 Despite the very high enantiopurity of the guest, the host–guest complex was observed to crystallize in the space group C 2/ c .…”

Encapsulation of Aromatic Compounds and a Non-Aromatic Herbicide into a Gadolinium-Based Metal–Organic Framework via the Crystalline Sponge Method

“…24,25 2), as a crystalline sponge by successfully encapsulating a range of simple small molecules such as methanol, pyridine and carvone. 26 The Gd MOF, 2, has several features that could be beneficial for use in the CSM. Firstly 2 crystallises in the low symmetry monoclinic space group C2/c, which reduces the chance of a guest molecule being located on a symmetry element.…”