Transcript Structure Comparison, Analysis and Validation

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
Small molecule and Protein Xtallography:Utrecht
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.
Example: Validation of a Deposited CIF


THE STABLE PENTAMETHYLCYCLOPENTADIENYL CATION
J.B.Lambert et al. Angew. Chem. Int. Ed. 2002, 41, 1429-1431
+
-
HOT STRUCTURE – FAST LANE PUBLICATION
Pentamethylcyclopentadienyl
Common Anionic Form
“New” Cationic Form
-
Assigned Bond types
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. [!!]
NOT SO HOT AFTER ALL !!
Editors Note in the next issue of Angewandte Chemie
Strange Bond Pattern and Ring pucker
D
?
o
D
Commonly misused “catch all’ explanation: PACKING EFFECTS ??
Double Bond
Example: Validation of a Deposited CIF


Corrected Structure
J.N. Jones et al.,Chem. Comm. 2002,1520-1521
Additional
H-Atoms
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.
STRUCTURE VALIDATION
IN 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.
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 …
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.
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.
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.
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?
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
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.
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)
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.
Problems Addressed by PLATON
S
Reflection Data (.fcf)
Sufficient Resolution
Completeness of the data set
Missed (Pseudo-) Merohedral Twinning
Absolute Structure, Flack Parameter,
Bijvoet pairs
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 ==>
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 noncentrosymmetric space group.
• Example from JACS =
Praseodymium complex
J.A.C.S. (2000),122,3413 – P1, Z = 2
CORRECTLY REFINED STRUCTURE
P-1, Z=2
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 %
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
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:
Entry from the CSD
S…S = 2 Ang ?
S
H
But with Space Group Symmetry
=> Different structure with S-S Bond !
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)
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
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’ ……
Additional Info
http://www.cryst.chem.uu.nl
(including a copy of this powerpoint presentation)
Thanks
for your attention !!