Refinement of organic crystal structures with multipolar electron scattering factors.

Barbara Gruza,Paulina Maria Dominiak,Joanna Krzeszczakowska,Michał Leszek Chodkiewicz

doi:10.1107/s2053273319015304

Barbara Gruza, Paulina Maria Dominiak + Show 2 more

Open Access

https://doi.org/10.1107/s2053273319015304

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Abstract

A revolution in resolution is occurring now in electron microscopy arising from the development of methods for imaging single particles at cryogenic temperatures and obtaining electron diffraction data from nanocrystals of small organic molecules or macromolecules. Near-atomic or even atomic resolution of molecular structures can be achieved. The basis of these methods is the scattering of an electron beam due to the electrostatic potential of the sample. To analyse these high-quality experimental data, it is necessary to use appropriate atomic scattering factors. The independent atom model (IAM) is commonly used although various more advanced models, already known from X-ray diffraction, can also be applied to enhance the analysis. In this study a comparison is presented of IAM and TAAM (transferable aspherical atom model), the latter with the parameters of the Hansen-Coppens multipole model transferred from the University at Buffalo Databank (UBDB). By this method, TAAM takes into account the fact that atoms in molecules are partially charged and are not spherical. Structure refinements were performed on a carbamazepine crystal using electron structure-factor amplitudes determined experimentally [Jones et al. (2018). ACS Cent. Sci. 4, 1587-1592] or modelled with theoretical quantum-mechanical methods. The results show the possibilities and limitations of the TAAM method when applied to electron diffraction. Among others, the method clearly improves model fitting statistics, when compared with IAM, and allows for reliable refinement of atomic thermal parameters. The improvements are more pronounced with poorer-resolution diffraction data.

Highlights

Until recently, the only techniques that routinely yielded atomic and near-atomic resolution structures of molecules were X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy
Single-particle cryo-electron microscopy can be used to determine near-atomic resolution structures of macromolecules that are either reluctant to crystallize or are difficult to crystallize in specific functional states
In order to discuss any results regarding the performance of various models in a proper description of electron scattering, it is very instructive to firstly examine how the electrostatic potential and electron density of a single carbamazepine molecule look according to direct density functional theory (DFT) calculations, or transferable aspherical atom model (TAAM)

Summary

Introduction

The only techniques that routinely yielded atomic and near-atomic resolution structures of molecules were X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. New technological and computational developments for transmission electron microscopes have made electron scattering based techniques legitimate candidates for routine 3D structure determinations at atomic resolution. Single-particle cryo-electron microscopy (cryo-EM) can be used to determine near-atomic resolution structures of macromolecules that are either reluctant to crystallize or are difficult to crystallize in specific functional states. Electron diffraction (ED), on the other hand, is currently the method of choice to study crystal structures and properties of nano-sized materials at atomic resolutions. These include materials for which it is difficult to obtain crystals of a size suitable for X-ray analysis, like pharmaceuticals, pigments, zeolites and macromolecules.

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