Crystal%20Structure%20Validation%20A%20Tool%20to%20distinguish%20GOOD%20and%20reliable%20single%20crystal%20studies%20from%20BAD%20and%20UGLY%20reports.

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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

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Small molecule and Protein XtallographyUtrecht
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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.

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Example Validation of a Deposited CIF
?
?
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THE STABLE PENTAMETHYLCYCLOPENTADIENYL
CATION J.B.Lambert et al. Angew. Chem. Int. Ed.
2002, 41, 1429-1431

-
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HOT STRUCTURE FAST LANE PUBLICATION
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Pentamethylcyclopentadienyl
Common Anionic Form
New Cationic Form
-
Assigned Bond types
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Enthusiastic Last Paragraph of CE-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
  cations track record, it might be safer to
  expect more surprises. !!

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NOT SO HOT AFTER ALL !!
Editors Note in the next issue of Angewandte
Chemie
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Strange Bond Pattern and Ring pucker
DoD
Double Bond ?
Commonly misused catch all explanation
PACKING EFFECTS ??
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Example Validation of a Deposited CIF
?
?
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Corrected StructureJ.N. Jones et al.,Chem. Comm.
2002,1520-1521
Additional H-Atoms
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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.

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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.

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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

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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.

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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.

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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.

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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?

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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

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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.

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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)

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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.

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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

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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 2004
  Organometallics (23, 3210-3217) paper gt

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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 ?

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Praseodymium complex
J.A.C.S. (2000),122,3413 P1, Z 2
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CORRECTLY REFINED STRUCTURE
P-1, Z2
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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

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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 CIFs and CCDC-FDAT

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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

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Entry from the CSD
SS 2 Ang ?
H
S
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But with Space Group Symmetry
gt Different structure with S-S Bond !
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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)

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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

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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

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Additional Info

• http//www.cryst.chem.uu.nl
• (including a copy of this powerpoint
  presentation)
• Thanks
• for your attention !!

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