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Ton Spek National Single Crystal Facility Bijvoet Center of Biomolecular Research

Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal Facility Bijvoet Center of Biomolecular Research Utrecht University The Netherlands MIT Feb 18,2006.

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Ton Spek National Single Crystal Facility Bijvoet Center of Biomolecular Research

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  1. Crystal Structure ValidationA Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal Facility Bijvoet Center of Biomolecular Research Utrecht University The Netherlands MIT Feb 18,2006

  2. Small molecule and Protein Xtallography:Utrecht

  3. Automated Structure Validation • Automated validation of crystal structures as part of the editorial process is currently implemented in one form or another by most if not all major chemical journals. • There are good scientific reasons for enforcing such a procedure as illustrated by the following real world example that apparently was not properly validated.

  4. Example: Validation of a Deposited CIF  

  5. THE STABLE PENTAMETHYLCYCLOPENTADIENYL CATION J.B.Lambert et al. Angew. Chem. Int. Ed. 2002, 41, 1429-1431 + -

  6. HOT STRUCTURE – FAST LANE PUBLICATION

  7. Pentamethylcyclopentadienyl Common Anionic Form “New” Cationic Form - Assigned Bond types

  8. Enthusiastic Last Paragraph of C&E-News … The [ .. chemists] are now exploring the reactivity of C5Me5+. “You can sit down and write lots of interesting reactions on paper,” [P.I.] says, and it will be interesting to see if the molecule reacts as expected. But considering this cation’s track record, it might be safer to expect more surprises. [!!]

  9. NOT SO HOT AFTER ALL !! Editors Note in the next issue of Angewandte Chemie

  10. Strange Bond Pattern and Ring pucker DoD Double Bond? Commonly misused “catch all’ explanation: PACKING EFFECTS ??

  11. Example: Validation of a Deposited CIF  

  12. Corrected StructureJ.N. Jones et al.,Chem. Comm. 2002,1520-1521 Additional H-Atoms

  13. Where did it go Wrong ? • First impression of the structure was likely based on a preliminary result (plot) without H-atoms. • Rushed as a short communication into the prestigious high impact journal Angewandte Chemie. • Ignoring all (theoretical) counter indications. • Apparently there was no experienced crystallographer involved as a referee ? • Apparently no unbiased automated CIF-validation was done.

  14. STRUCTURE VALIDATIONIN THE PAST • Single crystal structures were mostly determined by professional crystallographers using (slow) serial detectors (typically ~ 50 datasets/year). • Using (open source) software they knew in detail. • Structures were analyzed and discussed in great detail and all evidence was given in the paper. • Papers containing crystallographic results were generally refereed by fellow crystallographers.

  15. Crystallography Today - Diminishing number of professional small molecule crystallographers (sites, teaching). • Many crystal structures done by chemists with limited crystallographic background. • Using CCD detectors (~ 1000 datasets/year – when pushed and given enough ‘slaves’). • Crystal structures solved using Black-Box crystallographic firmware (SHELXTL etc.) • Near Future: Autosolve …

  16. Why Automated Validation? PROBLEMS: - See previous Cp*+ example. • Exploding # of structural papers to review. • Limited # of referees with sufficient time and crystallographic knowledge. • Limited supporting information available for the reviewer (footnote/deposited). • Papers including structural ‘evidence’ are increasingly refereed by non-crystallographers, unaware of the many potential pitfalls.

  17. SOLUTION The solution for the problem was pioneered by the International Union of Crystallography • Provide and archive structural data in computer readable CIF format. • Automated validation, with a computer generated report for authors and referees. • Journals enforcing a structure validation protocol. - All IUCr journals and most major chemical journals now implement validation procedures.

  18. THE CIF DATA STANDARD • Driving Force: Syd Hall (IUCr/ Acta Cryst C) • Early Adopted by XTAL & SHELX(T)L. • Currently: WinGX,Crystals,Texsan, Maxus etc. • Acta Cryst. C/E – Electronic Submission • Acta Cryst.:Automatic Validation at the Gate • CIF data available for referees for detailed inspection (and optional calculations). • Data retrieval from the WEB for published papers • CCDC – Deposition in CIF-FORMAT.

  19. VALIDATION QUESTIONS Single crystal validation addresses three important questions: 1 – Is the reported information complete? 2 – What is the quality of the analysis? 3 – Is the Structure Correct?

  20. IUCR-CHECKCIF SERVICE IUCR-TESTS: • MISSING DATA, PROPER PROCEDURE, QUALITY PLATON TESTS: • SYMMETRY, GEOMETRY, DISPLACEMENT PARAMETERS, VOIDS, TWINNING etc. ALERTS : • ALERT A - SERIOUS PROBLEM • ALERT B - POTENTIALLY SERIOUS PROBLEM • ALERT C - CHECK & EXPLAIN

  21. ALERT TYPES 1 - CIF Construction/Syntax errors, Missing or Inconsistent Data. 2 - Indicators that the Structure Model may be Wrong or Deficient. 3 - Indicators that the quality of the results may be low. 4 - Cosmetic Improvements, Queries and Suggestions.

  22. Problems Addressed by PLATON • Missed Higher Space Group Symmetry • Solvent Accessible Voids in the Structure • Unusual Displacement Parameters • Hirshfeld Rigid Bond test • Misassigned Atom Type • Population/Occupancy Parameters • Mono Coordinated/Bonded Metals • Isolated Atoms (e.g. O, H, Transition Metals)

  23. Problems Addressed by PLATON • Too Many Hydrogen Atoms on an Atom • Missing Hydrogen Atoms • Valence & Hybridization • Short Intra/Inter-Molecular Contacts • O-H without Acceptor • Unusual Bond Length/Angle • CH3 Moiety Geometry • To be extended with tests for new problems ‘invented’ by authors.

  24. Problems Addressed by PLATON Reflection Data (.fcf) • Sufficient Resolution • Completeness of the data set • Missed (Pseudo-) Merohedral Twinning • Absolute Structure, Flack Parameter, Bijvoet pairs S

  25. The Missed Symmetry Problem • Up to 10 % of the structures in space groups such as Cc have higher symmetry (e.g. C2/c, R-3c, Fdd2 etc.) than was originally reported. (To be Marshed is not good for your scientific reputation as a crystallographer). • MISSYM & PLATON/ADDSYM algorithm effectively addresses the problem. • Missed symmetry EXAMPLE from a 2004Organometallics (23, 3210-3217) paper ==>

  26. Why is description in a correct space group so important ? • Refinement in a too low symmetry group may result in geometry artifacts • In particular when a centro-symmetric structure is refined in a non-centrosymmetric space group. • Example from JACS =

  27. Praseodymium complex J.A.C.S. (2000),122,3413 – P1, Z = 2

  28. CORRECTLY REFINED STRUCTURE P-1, Z=2

  29. Structure Determination Artifacts • Pseudo-symmetry easily results in false structures. • Example: An Organometallic-AuCl compound from the CSD with the Cl in the wrong position  Very Short C-H..Cl ?! ALERTED by validation (C..Cl = 2.19 Ang) • Moving Cl to the correct position drops R from 4 to 2 %

  30. Validation with PLATON - Details: www.cryst.chem.uu.nl/platon • Driven by the file CHECK.DEF with criteria, ALERT messages and advice. • Use (UNIX): platon –u structure.cif • Result on file: structure.chk • Applicable on CIF’s and CCDC-FDAT

  31. Consult the CSD • It is a good idea to always consult the CSD for previous reports on structures related to the one at hand. • The statistics provided by VISTA (CCDC) can be very helpful for this. • However, be aware, such an analysis often shows outliers. Many of those appear to be errors. • Example: A search for short S..S contacts gave:

  32. Entry from the CSD S…S = 2 Ang ? H S

  33. But with Space Group Symmetry => Different structure with S-S Bond !

  34. COMMENTS • Validation should not be postponed to the publication phase. • All validation issues should be taken care of during the analysis. • Everything unusual in a structure is suspect, mostly incorrect (artifact) and should be investigated and discussed in great detail and supported by independent evidence. - The CSD can be very helpful when looking for possible precedents (but be careful)

  35. CONCLUSION Validation Procedures are excellent Tools to: • Set Quality Standards (Not just on R-Value) • Saves a lot of Time in Checking, both by the Investigators and the Journals (referees) - Point at Interesting Features (Pseudo-Symmetry, short Interactions etc.) to be discussed. • Surface a problem that only an experienced Crystallographer might be able to Address. • Proof the ‘Routine’ Status of the Determination in the Hands of its Investigator

  36. Residual Problem EDUCATION Response of an author of a structural paper submitted to the crystallographic journal Acta Cryst. to an enquiry from a referee on the reported space group: Please teach me, what does in mean ‘ space group incorrect’ ……

  37. Additional Info http://www.cryst.chem.uu.nl (including a copy of this powerpoint presentation) Thanks foryourattention !!

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