Absolute configuration determination of pharmaceutical crystalline powders by MicroED via chiral salt formation

Abstract

Microcrystal electron diffraction (MicroED) has established its complementary role alongside X-ray diffraction in crystal structure elucidation. Unfortunately, kinematical refinement of MicroED data lacks the differentiation power to assign the absolute...

Electron Diffraction of 3D Molecular Crystals

“…Regardless, in the absence of appreciable dynamical signal, 3D ED remains perfectly capable of inferring stereochemistry relative to an internal chiral reference, such as another stereocenter whose absolute configuration is known a priori . One viable strategy to achieve this involves cocrystallization with enantiopure additives …”

Computational methods and points for attention in absolute configuration determination

“…With the rapid development of high performance computers and computational methods, including software, an increasing number of experimental chemists have tried to use computational methods such as optical rotation (OR, including optical rotatory dispersion (ORD)), electronic circular dichroism (ECD)-also known as CD before vibrational circular dichroism (VCD) was widely used-and magnetic shielding constants-nuclear magnetic resonance (NMR)-to explain and/or assign absolute or relative configurations for various compounds and polymers (fibers) (Kurouski et al, 2014;Marty et al, 2014;Li et al, 2016a;Fernández et al, 2019), including metallic complex (Merten et al, 2014;Li et al, 2019a). Reports of such work in bioactive compounds and natural products chemistry has dramatically increased (Sherer et al, 2014a;Sherer et al, 2014b;Yang et al, 2018), while traditional methods, such as Mosher ester (Hoye et al, 2007;Zheng et al, 2019) and X-rays (Wang et al, 2022)-in which Cu-Kα (1.5418 Å) radiation is preferred to Mo-Kα (0.7107 Å) radiation, due to its stronger anomalous scattering effect (Bijvoet et al, 1951)-are also widely used in absolute configuration (AC) studies. Natural products have also been called the "engines of its development and .…”

Accuracy of quantum chemistry structures of chiral tag complexes and the assignment of absolute configuration

“…The physical chemistry community continues to develop spectroscopy methods to assign the absolute configuration of molecules. [16][17][18][19][20][21] Spectroscopy methods ultimately require quantum chemistry predictions of the spectrum for analysis. Perhaps the most successful technique is vibrational circular dichroism (VCD) and its related method of Raman optical activity.…”