October 28, 2022

Absolute configuration determination of SMTP-7 via microcrystal electron diffraction (MicroED)

NIS Mountain Hero

Direct absolute configuration determination of a drug candidate bearing five chiral centers, SMTP-7, is lacking. With only few-micron-sized powders available, we assigned the absolute configuration of SMTP-7 via MicroED analysis through kinematical refinement with additional chiral information and directly through the recently developed dynamical refinement approach.

Microcrystal electron diffraction (MicroED) provides an alternative solution to crystal structure determination in case scXRD is impossible. The advantage of MicroED lies in the minimal sample preparation requirements that only sub-micron crystalline powders are sufficient to yield reasonable crystal structures. However, unlike scXRD, kinematically refined ED data does not produce significant anomalous signals to distinguish the enantiomeric pair of solutions. Therefore, we previously demonstrated that incorporation of chiral information in material (e.g. chiral salt formation) can be used to derive the absolute configuration. Excitingly, computational tools of dynamical refinement on ED data have been recently developed and utilized to directly assign the absolute configuration of model organic molecules although a genuinely unknown example is yet to be explored with this approach.


Wang, Bo; Lin, Yiqing; Absolute configuration determination of SMTP-7 via microcrystal electron diffraction (MicroED); Royal Society of Chemistry 2022; doi: 10.1039/D2CC05218K

Bo Wang,Yiqing Lina
NIS Mountain Hero