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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

Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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Page 1: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Crystal Structure Validation

A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports.

Ton Spek

National Single Crystal FacilityBijvoet Center of Biomolecular Research

Utrecht University

The NetherlandsMIT Feb 18,2006

Page 2: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Small molecule and Protein Xtallography:Utrecht

Page 3: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 4: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Example: Validation of a Deposited CIF

Page 5: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

THE STABLE PENTAMETHYLCYCLOPENTADIENYL CATION

J.B.Lambert et al. Angew. Chem. Int. Ed. 2002, 41, 1429-1431

+ -

Page 6: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

HOT STRUCTURE – FAST LANE PUBLICATION

Page 7: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Pentamethylcyclopentadienyl

-

Common Anionic Form “New” Cationic Form

Assigned Bond types

Page 8: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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. [!!]

Page 9: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

NOT SO HOT AFTER ALL !!

Editors Note in the next issue of Angewandte Chemie

Page 10: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Strange Bond Pattern and Ring pucker

Commonly misused “catch all’ explanation: PACKING EFFECTS ??

DoD

Double Bond ?

Page 11: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Example: Validation of a Deposited CIF

Page 12: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Corrected StructureJ.N. Jones et al.,Chem. Comm. 2002,1520-1521

Additional H-Atoms

Page 13: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 14: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 15: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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 …

Page 16: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 17: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 18: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 19: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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?

Page 20: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

IUCR-CHECKCIF SERVICEIUCR-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

Page 21: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 22: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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)

Page 23: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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.

Page 24: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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

Page 25: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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 ==>

Page 26: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal
Page 27: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal
Page 28: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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 =

Page 29: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Praseodymium complex

J.A.C.S. (2000),122,3413 – P1, Z = 2

Page 30: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

P-1, Z=2

CORRECTLY REFINED STRUCTURE

Page 31: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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 %

Page 32: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal
Page 33: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal
Page 34: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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

Page 35: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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:

Page 36: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Entry from the CSD

HSS…S = 2 Ang ?

Page 37: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

But with Space Group Symmetry

=> Different structure with S-S Bond !

Page 38: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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)

Page 39: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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

Page 40: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

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’ ……

Page 41: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal

Additional Info

http://www.cryst.chem.uu.nl (including a copy of this powerpoint presentation)

Thanks

for your attention !!

Page 42: Crystal Structure Validation A Tool to distinguish GOOD and reliable single crystal studies from BAD and UGLY reports. Ton Spek National Single Crystal