Should we remediate small molecule structures? If so, who should do it?

ABSTRACT

Problems can arise in crystallographic databases with errors and omissions in the representation of data that impede searches, and with errors in the actual data. While the Cambridge Crystallographic Data Centre with its Improvement Projects has solved many of the first category of problems, errors in atomic coordinates and other crystallographic data are surprisingly common. Although modern software warns of many types of error, such errors appear even in recently deposited Crystallographic Information Files. Richard Marsh found many examples of missed symmetry in assignment of the space group; such errors are now waning. Hydrogen atoms are commonly placed in calculated positions. Particularly for OH and NH groups involved in hydrogen bonds, occupancy factors may need to be reduced to 0.5 or the hydrogen atom positions may require amendment. Examples of acids and imidazole derivatives are provided, showing that sometimes only consideration of bond distances and angles at the heteroatom can distinguish between OH or NH and unprotonated O or N. Significant work by other researchers correcting mis-positioned hydrogen atoms in dihydrogen phosphates and water aggregates as well as mis-identified elements is also summarized. This review concludes with some suggestions for more comprehensive detection and correction of errors in deposited data.

KEYWORDS:

• Erroneous structures
• carboxylic acids
• imidazoles
• preventing errors
• rectifying errors

Acknowledgement

I thank my colleagues at the CCDC for helpful discussions.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Notes on contributors

Carl H. Schwalbe

Carl H. Schwalbe received his AB in Chemistry from Oberlin College and his AM from Harvard University. His PhD research at Harvard was supervised by Nobel laureate William N. Lipscomb. After postdoctoral research at the Max Planck Institute for Experimental Medicine in Göttingen, Germany, he joined Aston University in Birmingham in 1972 as a Lecturer in Pharmacy, eventually becoming Professor of Medicinal Chemistry. On retiring in 2010, he was appointed Honorary Senior Research Fellow at the Cambridge Crystallographic Data Centre. His research interests involve the use of structural information, mainly obtained by X-ray crystallography, to explain the activity of drugs and the properties of solid dosage forms. In periods of sabbatical leave at Brookhaven National Laboratory and Oxford University, he also applied neutron diffraction and computational chemistry. In 2008 Carl H. Schwalbe became the editor of Crystallography News, the quarterly news magazine of the British Crystallographic Association, He periodically writes about significant people in the history of crystallography and has authored or co-authored Historical Reviews about the Braggs, June Sutor, Lars Vegard and Arthur Lindo Patterson in this journal. Since 2015 he has annually given didactic presentations on incorrectly positioned hydrogen atoms and their possible correction to American Crystallographic Association meetings.