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

Abstract

Single crystal X-ray diffraction (SCXRD) is arguably the most definitive method for molecular structure determination, but it is often challenged by compounds that are liquids or oils at room temperature or do not form crystals adequate for analysis. Our laboratory previously reported a simple, cost-effective, single-step crystallization method based on guanidinium organosulfonate (GS) hydrogen bonded frameworks for structure determination of a wide range of encapsulated guest molecules, including assignment of the absolute configuration of chiral centers. Herein, we expand on those results and report a head-to-head comparison of the GS method with adamantoid "molecular chaperones", which have been reported to be useful hosts for structure determination. Inclusion compounds limited to only two GS hosts are characterized by low R₁ values and Flack parameters, infrequent disorder of the host and guest, and manageable disorder when it does exist. The structures of some target molecules that were not included or resolved using the adamantoid chaperones were successfully included and resolved by the GS hosts, and vice versa. Of the 32 guests attempted by the GS method, 31 inclusion compounds afforded successful guest structure solutions, a 97% success rate. The GS hosts and adamantoid chaperones are complementary with respect to guest inclusion, arguing that both should be employed in the arsenal of methods for structure determination. Furthermore, the low cost of organosulfonate host components promises an accessible route to molecular structure determination for a wide range of users.

Figure 1

Top: The typical quasihexagonal GS sheet (top), illustrating the hydrogen-bonded “hinge” that allows facile puckering of the GS sheet allowing for “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: The two guanidinium organosulfonate hosts used here.

Figure 2

Target guest molecules included and fully refined in GCHMS or G₂1,5-NDS hosts, listed in order of increasing molecular weight. The GS framework corresponding to each target molecule and the R₁ values are provided. Flack parameters (x) are provided for structures with chiral guests. The near-zero value and high precision of the Flack parameters for inclusion compounds provide confidence in the assignment of the absolute configuration. Guests denoted in red correspond to those investigated with “molecular chaperones”.^, Compound 5 contains both stereoisomers of cis-rose oxide in equal amounts; the stereochemistry is not denoted here for the sake of clarity. The structure of eugenol in 28a and 28b could not be resolved due to guest disorder. Examples 8S and 24S denote data collected using synchrotron radiation. Examples of the structure determination of 21 other guests (not shown here) using GS hosts have been reported elsewhere.^−,,

Figure 3

Illustrative crystal structures. (A–C) (G₂1,5-NDS)⊃(R)-2-pentanol (7) and (D–F) (GCHMS)₄⊃cis-rose oxide (24), depicted as ball-and-stick (top), target guest molecules as space filling (middle), and guests with ellipsoids at 50% probability (bottom).