Structure Validation in Chemical Crystallography

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Structure ValidationinChemical Crystallography

• Ton Spek,
• Bijvoet Centre for
• Biomolecular Research,
• Utrecht University,
• The Netherlands.
• CCP4-Leeds, 5-Jan.-2008.

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Overview of this Talk

• Introduction to the Problems that are addressed
  by Structure Validation in Chemical
  Crystallography
• The currently implemented IUCr Solution
• Evaluation of the Performance
• Possible Future work and Extensions
• Summary Conclusion

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Chem. Cryst. 40 Years Ago (when I started in
Xtallography)

• Datacollection, Structure Solution, Refinement
  and Publication took generally several months or
  more.
• For my first structure I even had to write my own
  Direct Methods program to solve it.
• Software was not a Black Box. Ad-hoc software
  development was part of the job.
• Paper review was done in those days by
  experienced crystallographers and took months to
  publication.

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Today

• A Routine Datacollection, followed by
• Automated Structure Determination,
• SHELXL Refinement,
• PublCIF Paper Preparation and
• Electronic Submission to Acta Cryst.,
• May take an experienced crystallographer
• just 1 day for an Acta Cryst. E paper.

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Number of Yearly Published Chem. Cryst.
Structures

• 1967 936
• 2007 more than 30000
• CSD Nov 2007 450000 entries
• More growth expected (China, India)

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Announced Aug 2007 Tabletop Black Box Smart
X2S
Mount Crystal in a Vial
Structure ?
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Are all those 450000 Structures Correct and
Reliable?

• Unfortunately not.
• The result of many searches in the CSD for
  structures that are related to the structure
  under investigation will include outliers, many
  of which turn out to be at least suspect.
• Following are just three of the examples of
  chemically wrong structures that obviously passed
  the refereeing system.

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Published with Wrong Composition
B
O
BORAX !
B
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Entry from the CSD (IDAKUT)
Found during search in CSD for short inter SS
Contacts
S
H
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But with Space Group Symmetry
gt Different compound with S-S Bond !
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Searching for structures with a Methyl Moiety
bridging two metals
Structure of a strange CH3 Bridged Zr Dimer
Paper has been cited 47 times !
So can we believe this structure?
The Referees did !
But
H .. H 1.32 Ang. !
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Comment

• The methyl hydrogen atoms are expected outside
  the Zr2C2 ring (and indeed have been found in
  similar structures)
• Referees likely had no access to (or did not
  access) the primary data other than the ORTEP
  illustration in the paper.
• General problem A limited number of experts is
  available to referee too many structural papers
  that offer only limited primary (deposited) data.

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Partial Solution

• A solution for the structure validation
  problem was pioneered by the International Union
  of Crystallography
• Provide and archive crystallographic data in the
  computer readable CIF standard format.
• (Driving force Syd Hall, Editor Acta Cryst.
  C)
• Implement Automated Validation, with a computer
  generated report for authors, editors and
  referees.

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The CIF Data Standard

• - Early Adopted in 1993 by SHELX(T)L and
  subsequently other packages.
• Around 1995 CIF-Format Electronic Submission to
  Acta Cryst. C/E
• Ten Years Ago Automatic Validation (and possible
  return to sender) of Acta Cryst. C E papers at
  the Gate.
• CIF HKL data are available for referees for
  detailed inspection (and optional calculations).
• Data retrieval from the WEB for published papers

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VALIDATION QUESTIONS

• Single crystal validation addresses three
• simple but 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 WEB-Service

• http//checkcif.iucr.org reports the outcome of
• IUCr standard tests
• Consistency, Missing Data, Proper Procedure,
  Quality, Comparison against test criteria etc.
• Additional PLATON based tests
• Missed Symmetry, Voids, Geometry, Hydrogen
  atoms, Displacement Parameters, etc.

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ALERT LEVELS

• CheckCif Report in terms of a list of ALERTS
• ALERT A Serious Problem
• ALERT B Potentially Serious Problem
• ALERT C Check Explain
• ALERT G Verify or Take Notice

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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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EXAMPLE OF PLATON GENERATED ALERTS FOR A
RECENT PAPER PUBLISHED IN J.Amer.Chem.Soc. (2007)
Attracted special attention in Chemical and
Engineering News
(Referees obviously did not Bother)
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Problems Addressed by PLATON/CIF-CHECK

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

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More 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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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 (Y. LePage) PLATON/ADDSYM algorithm
  addresses the problem.
• - Next Slide Example ?

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WRONG SPACEGROUP
J.A.C.S. (2000),122,3413 P1, Z 2
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CORRECTLY REFINED STRUCTURE
P-1, Z2
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Example of Change of Space Group ALERT
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Misoriented O-H

• The O-H moiety is generally, with very few
  exceptions, part of a D-H..A system.
• An investigation of structures in the CSD brings
  up many exceptions.
• Closer analysis shows that misplacement of the
  O-H hydrogen atom is in general the cause.
• Molecules have an environment in the crystal !
• Example ?

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Validation Looks at inter-molecular contacts
Unsatisfactory Hydrogen Bond Network
Correct !
ALERT !
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Solvent Accessible Void of 235 Ang3 out
of 1123 Ang3
Often Not Accounted for in the Refinement
Model
High R-value
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Additional Problems Addressed byPLATON/FCF-CHECK

• With information from .cif and .fcf files
• Report on the resolution of the data
• Report about randomly missing data
• Check the completeness of the data (e.g. for
  missing cusps of data)
• Report on Missed (Pseudo) Merohedral Twinning
• Report on Friedel Pairs and Absolute Structure
  (comparison of Hooft y with Flack x parameter
  values)

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Missed (Pseudo) Merohedral Twinning

• A tool (TwinRotMat) in PLATON automatically
  analyses a reported structure for missed twinning
• Example ?

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Evaluation and Performance

• The validation scheme has been very successful
  for Acta Cryst. C E in setting standards for
  quality and reliability.
• Most major chemical journals currently have some
  form of a validation scheme implemented.
• But does it solve all problems

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Some Recent Statistics

• Validation CSD Entries 2006 early 2007
• Number of entries 35760
• of likely Space Group Changes 384
• of structures with (unaccounted for ?) voids
  3354
• Numerous problems with H, O, OH, H2O etc., etc, .

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Problems to be Addressed

• Synthetic Chemist View Addressing
  Crystallographic Details holds up the Publication
  of Important Chemistry
• Author Question
• What does it mean Spacegroup Incorrect
• Crystallographic Education (beyond Pushbutton and
  Black Box)
• Referees that know how to handle ALERTS

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Possible Future Extensions

• Validation of Structures from Powder Data
• Validation of Inorganic Compounds
• Validation of Incommensurate Structures
• Validation of Charge Density Studies
• Automated check against (average) geometry in the
  CSD
• Check for fabricated data ?

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Summary Conclusions

• Validation Procedures are excellent Tools to
• Set Quality Standards (Not just on R-Value)
• Save a lot of Time in Checking, both by the
  Investigators and the Journals (referees)
• Point at Interesting Structural Features
• (Pseudo-Symmetry, short Interactions etc.) to
  be discussed.
• Surface a problem that only an experienced
  Crystallographer might be able to Address
• Proof of a GOOD structure.

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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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Example of a PLATON/Check Validation Report Two
ALERTS related to the misplaced Hydrogen Atom