Transcript Automatic Detection of Poor or Incorrect Single Crystal

Structure Validation:
How to distinguish GOOD and
reliable single crystal structures
from BAD and UGLY reports
A.L.Spek
Utrecht University
The Netherlands
1964 Nobel Lecture Dorothy Hodgkin
…. [The] great advantage of X-ray
analysis as a method of chemical
structure analysis is its power to
show some totally unexpected and
surprising structure with, at the
same time, complete certainty. ..
With Complete Certainty ?
• Yes, in most cases, in particular in the hands of
experienced investigators.
• No, when proper scientific procedures have been
ignored.
• This presentation will address a number of
obvious cases where proper procedures were
ignored, resulting in erroneous science.
• Automated Structure Validation is offered as a tool
to add a qualifier Good (Correct), Bad(False) or
Ugly(Poor) to a structural study.
THE STABLE PENTAMETHYLCYCLOPENTADIENYL CATION
J.B.Lambert et al. Angew. Chem. Int. Ed. 2002, 41, 1429-1431
HOT STRUCTURE – FAST LANE PUBLICATION
Pentamethylcyclopentadienyl
Anion (Cp*-)
-
PENTAMETHYLCYCLOPENTADIENYL CATION
ASSIGNED BOND-TYPES
Enthusiastic Last Paragraph of
C&E-News
… The Northwestern chemists are now
exploring the reactivity of C5Me5+. “You
can sit down and write lots of interesting
reactions on paper,” Lambert 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
PACKING EFFECTS ??
Double Bond ?
Corrected Structure
J.N. Jones et al.,Chem. Comm. 2002,1520-1521
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 counter evidence.
• No experienced crystallographer as referee ?
• No unbiased automated CIF-validation.
Validation of the Deposited CIF


WHY AUTOMATED
STRUCTURE VALIDATION?
- See Previous Case Study.
IN THE PAST
- Single crystal structures determined by
professional crystallographers (Dorothy Hodgkin)
- Using serial detectors (~ 50 datasets/year).
- Using (open source) software they knew in detail.
- Structures were analyzed and discussed in great
detail.
- Papers containing crystallographic results were
refereed by fellow crystallographers.
Why Automated Validation?
-
-
PRESENT:
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.)
Why Automated Validation?
-
PROBLEMS:
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 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.
- IUCr journals and most major 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
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
Friedel 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).
- MISSYM & PLATON/ADDSYM algorithm
addresses the problem.
- EXAMPLE ==>
Praseodymium complex
J.A.C.S. (2000),122,3413 – P1, Z = 2
CORRECTLY REFINED STRUCTURE
P-1, Z=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
Example of Misplaced Hydrogen Atom
Two ALERTS related to the misplaced Hydrogen Atom
Unsatisfactory Hydrogen Bond Network
Satisfactory Hydrogen Bond Network with new H-position
Characterization of compound isolated from marine invertebrate
Lindquist et al., J. Amer. Chem. Soc. (1991),113,2303-2304.
Synthesis: Li et al. (2001) Angew. Chem. 113, 4901 ->Surprise
Solution of the riddle: Li et al. (2001) Angew. Chem. 113,4906
O --> N-H (Analysis of the Displacement Ellipsoids)
Automatic Validation of the coordinate data taken from the CSD
Result: Alert on short intermolecular O…O Contact
O
N
Infinite hydrogen bonded chain
N-H…O=C
Wrong Structure
• Sometimes automatic procedures can come up
with ‘reasonably looking’ but wrong structures.
• Structure validation software should send out
proper ALERTS to the investigators
(e.g. IUCr Checkcif)
• Example (Structure submitted to Acta Cryst. C):
The chemist involved expects a Cu-complex, so
that is what he reports … (confirmed by X-ray
crystallography !) and tries to publish … and
fortunately caught by a knowledgeable referee …
Cu not Coordinated =>
R<7%
ORTEP of the False Structure
R<6%
Ortep of the Correct Structure
Thus …
• The original paper indeed mentioned an
interesting uncoordinated Cu2+ but left it with this
statement.
• The chemistry changed from [Cu]2+[L]2- to
[L]+[Br]- by also adding some missed Hydrogen
atoms.
• HBr was used in the synthesis.
• Various ALERTS pointed to the problem but
ignored by the authors.
• Interestingly, the color of the crystal changed from
green to colorless in the revised paper …..
Entry from the CSD
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 #1
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 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
Conclusion #2
Dorothy Hodgkins claim that X-ray
crystallography can deliver new science is
still valid as it was in 1964,
Given:
- Correct procedures
- Structure validation
- Education
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
Thanks
for your attention !!