title: Ab initio structure determination of nanocrystals of organic pharmaceutical compounds by electron diffraction at room temperature using a Timepix quantum area direct electron detector.
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).
authors.affiliation: Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van Genderen
authors.affiliation: Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors.forename: M T B
authors.initials: MT
authors.lastname: Clabbers
authors.affiliation: Nanomegas SPRL, Boulevard Edmond Machtens 79, B 1080, Brussels, Belgium.
authors.forename: P P
authors.initials: PP
authors.lastname: Das
authors.affiliation: Department of Physics and Energy, Materials and Surface Science Institute (MSSI), University of Limerick, Limerick, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Stewart
authors.affiliation: Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Nederlof
authors.affiliation: Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors.forename: K C
authors.initials: KC
authors.lastname: Barentsen
authors.affiliation: Nanomegas SPRL, Boulevard Edmond Machtens 79, B 1080, Brussels, Belgium.
authors.forename: Q
authors.initials: Q
authors.lastname: Portillo
authors.affiliation: Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors.forename: N S
authors.initials: NS
authors.lastname: Pannu
authors.affiliation: Nanomegas SPRL, Boulevard Edmond Machtens 79, B 1080, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Nicolopoulos
authors.affiliation: Biology and Chemistry, Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), 5232 Villigen, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Gruene
authors.affiliation: Biophysical Structural Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: Abrahams
mesh_terms: D002220:Carbamazepine / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D009525:Niacin / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D009930:Organic Chemicals; D009525:Niacin; D002220:Carbamazepine
keywords: Timepix quantum area detector; carbamazepine; electron diffraction structure determination; electron nanocrystallography; nicotinic acid