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.

Fig. 1

GS framework components. Top: the typical quasi-hexagonal GS sheet, illustrating the hydrogen-bonded hinge between hydrogen-bonded major ribbons (one of these is highlighted in gray) that allows facile puckering of the GS sheet with concomitant shrink-wrapping around guests in the inclusion cavities. The R substituents on the sulfur atoms denote organic groups that can project from either side of the GS sheet. Bottom: Guanidinium organosulfonates used here

Fig. 2

Schematic representations of host frameworks appearing herein. a–c Guanidinium disulfonate simply brick, zigzag brick, and crisscross bilayer architectures. d Guanidinium monosulfonate continuously layered architecture. e Tricylindrical architecture observed for the guanidinium tri(4-sulfophenyl)benzene host (G₃TSPHB)

Fig. 3

Target molecules, in GS frameworks, characterized by single crystal X-ray diffraction. The GS framework(s) corresponding to each target molecule and the R₁ values for observable reflections are provided. Flack parameters (x) are given for compounds that crystallized in chiral space groups. Values of x near 0.5 observed for achiral guests are consistent with twinning. The near-zero value and high precision of the Flack parameters (x) for inclusion compounds with chiral guests provides confidence in the assignment of absolute configuration. The deacetylated pancuronium was trapped as a hydrolysis product of pancuronium during crystallization, but without a conventional GS framework

Fig. 4

Illustrative crystal structures of GS inclusion compounds. These are depicted as stick figures that illustrate the 100% occupancy (left panel), the target guest molecules as space filling (center), and ORTEP representations of the guests. a–c (G₂NDS) ⊃ (3aR)-( + )-Sclareolide (5); d–f (G₂NDS) ⊃ (drospirenone)(methanol)_0.84(H₂O)_0.1 (6); g–i (G₂BDPYDS) ⊃ (progesterone) (7b). The stick renderings in the leftmost panels reveal the 100% occupancy of target guest molecules in the inclusion cavities and the center panel illustrates the substantial contribution of the guests to the total crystal volume