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

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.