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使用Timepix量子面积直接电子探测器在室温下通过电子衍射对有机药物化合物纳米晶体进行从头算结构测定。

Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector.

作者信息

van Genderen E, Clabbers M T B, Das P P, Stewart A, Nederlof I, Barentsen K C, Portillo Q, Pannu N S, Nicolopoulos S, Gruene T, Abrahams J P

机构信息

Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.

Nanomegas SPRL, Boulevard Edmond Machtens 79, B 1080, Brussels, Belgium.

出版信息

Acta Crystallogr A Found Adv. 2016 Mar;72(Pt 2):236-42. doi: 10.1107/S2053273315022500. Epub 2016 Feb 5.

DOI:10.1107/S2053273315022500
PMID:26919375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4770873/
Abstract

Until recently, structure determination by transmission electron microscopy of beam-sensitive three-dimensional nanocrystals required electron diffraction tomography data collection at liquid-nitrogen temperature, in order to reduce radiation damage. Here it is shown that the novel Timepix detector combines a high dynamic range with a very high signal-to-noise ratio and single-electron sensitivity, enabling ab initio phasing of beam-sensitive organic compounds. Low-dose electron diffraction data (∼ 0.013 e(-) Å(-2) s(-1)) were collected at room temperature with the rotation method. It was ascertained that the data were of sufficient quality for structure solution using direct methods using software developed for X-ray crystallography (XDS, SHELX) and for electron crystallography (ADT3D/PETS, SIR2014).

摘要

直到最近,通过透射电子显微镜对束敏感的三维纳米晶体进行结构测定时,为了减少辐射损伤,需要在液氮温度下收集电子衍射断层扫描数据。本文表明,新型Timepix探测器结合了高动态范围、非常高的信噪比和单电子灵敏度,能够对束敏感的有机化合物进行从头相位分析。使用旋转法在室温下收集了低剂量电子衍射数据(约0.013 e⁻ Å⁻² s⁻¹)。经确定,这些数据的质量足以使用为X射线晶体学(XDS、SHELX)和电子晶体学(ADT3D/PETS、SIR2014)开发的软件,通过直接法来解析结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/b3c6dd79c957/a-72-00236-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/5964eb4cdca2/a-72-00236-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/da4c22210c4f/a-72-00236-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/2d5163a05943/a-72-00236-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/b3c6dd79c957/a-72-00236-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/5964eb4cdca2/a-72-00236-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/da4c22210c4f/a-72-00236-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/2d5163a05943/a-72-00236-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcc7/4770873/b3c6dd79c957/a-72-00236-fig4.jpg

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