Validation and checking of crystal structures

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Validation and checkingof crystal structures
Alexander J. Blake, University of Nottingham,
UK and Anthony Linden, University of Zurich,
Switzerland
This presentation contains material from the
following lectures American Crystallographic
Association Annual Meeting, Los Angeles, July
2001 International Union of Crystallography
Congress, Geneva, August 2002 University of
Natal, Pietermaritzburg, South Africa, August
2003 ACS 226th National Meeting, New York,
September 2003 British Crystallographic
Association, Chemical Crystallography Group
Meeting, Cambridge, November 2003 European
Crystallographic Meeting, Budapest, August 2004
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How do we know whether this structure is correct
and reliable?
G. Pattenden (Nottingham)
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OUTLINE

• Overview validation and checking
• Validation for Acta C, etc
• Myths and misunderstandings
• Validation for other journals
• The limits of validation

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Validation involves comparison against a set of
test criteria

• Do cell volume and cell parameters match?

• Do bonded atoms have compatible Uij values?

• Has the refinement converged?

• Is the space group correct?

• Are the assigned atom types correct?

etc, etc, etc
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Valid-ation

• Correct
• Appropriate
• Defensible

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Checking is additional to validation

• Does the structure make sense to you?

• Does the structure look right?

• Do chemically equivalent bonds agree?

• Are all CIF entries complete and correct?

7
Automated data validation with checkCIF or PLATON

• Checks for
• CIF construction and syntax errors
• missing information
• parameters outside expected norms
• conformation with convention

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ALERT LEVELS
A Serious attention essential Item omitted
or large deviation from norm
Alert A No crystal dimensions have been
given Alert A Ratio of Tmax/Tmin expected is gt
1.30 An absorption correction is
required. Alert A Atom C58A ADP max/min Ratio
18.00
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ALERT LEVELS
B Significant action needed? Item is a
significant or unexpected outlier
Alert B The formula has elements in wrong
orderAlert B ADDSYM detects Cc to Fdd2
transformationAlert B Refined extinction
parameter lt 1.9sAlert B Structure contains VOIDS
of 130.00 Å3
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ALERT LEVELS
C Outside expected norms examine May appear
trivial, but do not dismiss out of hand - an
extensive list may indicate problems
Alert C Moiety formula not givenAlert C Short
inter X...Y contact O7...C1 2.96 ÅAlert
C Low U(eq) as compared to neighbors
C1Alert C D-H without acceptor N2H2
?
?
C1 and N2 should be N and C, respectively
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ALERT LEVELS
G General issues check
ALERT_3_G  The ratio of expected to reported
Tmax/Tmin (RR') is lt 0.75 Tmin and Tmax
reported      0.062     0.155 Tmin' and Tmax
expected     0.385     0.609
RR'       0.633  Please check that
your absorption correction is appropriate. 
380 ALERT 4 C Likely Unrefined X(sp2)-Methyl
Moiety .... C18 412 ALERT 2 C Short Intra XH3 ..
XHnH19B .. H30A 1.81 Ang. 720 ALERT 4 C Number
of Unusual/Non-Standard Label(s) .... 1
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A/B/C indicate the seriousness of the problem
ALERT Type 1 CIF construction/syntax error,
inconsistent or missing data ALERT Type 2
Indicator that the structure model may be
wrong/deficient ALERT Type 3 Indicator that
the structure quality may be low ALERT Type 4
Cosmetic improvement, query or suggestion
Not all combinations are logical, for example 4 A
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Sources of outlier parameters

• Unresolved feature (e.g., untreated disorder)
• Artefact due to limited data quality
• Inadequate procedures (e.g., poor corrections)
• Incorrect structure (e.g., wrong space group)
• A genuinely unusual observation!!

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What does validation software do?

• Identifies possible problems via ALERTs

• Provides explanations of ALERTs

• Suggests interpretations and possible solutions

• Not just for authors
• referees use it for assessment
• authors need to be aware of this
• how appropriate are IUCr criteria?

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When to validate?

• software for data collection, refinement, etc
• - should do its own validation
• use PLATON in final stages of determination
• validate raw CIF from the refinement program
• must validate the final version as well
• avoids problems at submission, refereeing, etc

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Looking at the structure
A visual examination can often be revealing here
there are some extreme ellipsoids which are also
incompatible with a rigid bond model
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A pretty picture, but what about the numbers
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1.369 Å
1.441 Å
1.390 Å
1.897 Å
in fact the bond lengths match the values
expected
Br
P.J. Cox, RGU, Aberdeen
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Less satisfactory
Ordered t-butyl group has all C-C distances
around 1.52 Å
Within the disordered group the range is 1.49 to
1.60 Å
Need (better) restraints?
Anon
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VALIDATION/CHECKING PROCEDURE

1. Check the CIF from refinement using PLATON
2. Augment CIF using e.g. XCIF and enCIFer
3. Re-check the CIF using PLATON or checkCIF
4. Look at ellipsoid plots from several directions
5. Check bond lengths are sensible and consistent
6. After any changes, re-check the CIF

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Validation and IUCr Journals
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Pre-electronic times

• Results tables largely created by hand
• only manual checking (if any)
• laborious and time-consuming
• hard to ensure consistent treatment
• vital matters were easily overlooked
• any revisions required laborious re-checking

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Early 1990s - CIF introduced

• allows automatic creation of tables
• enables full electronic submission/processing
• increases efficiency, faster publication times
• automates many editorial tasks
• improves appearance of the journal

? permits automated validation ?
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Automation of syntax and data checks

• authors get instant, anonymous feedback
• can detect and fix problems before submission
• fewer, shorter revision cycles
• consistent application of acceptance criteria
• editors/referees can focus on science
• RESULT faster publication times

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Authors working with CHECKCIF
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If you still get A alerts

• is there a sound scientific basis for the
  outlier?
• put Validation Response Form (VRF) into CIF
• submit CIF
• CIF ? Validation Co-editor (Acta C) ?
  Co-editor (Acta B or Acta E)

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Assessment of VRF

• VRF allows for fine-tuning

• validation criteria need some flexibility

• looking for sound scientific reasoning

• sound explanation? Pass the CIF

• otherwise suggest possible remedial action

We try to be helpful and informative !
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A valid riposte
Alert B ADDSYM detects additional (pseudo)
symmetry element I Author Response This
additional symmetry element does not hold true
for one of the ether bridges, as discussed in
the text.
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An inadequate answer

• Alert A lt 85 complete (theta max?)
• Author Response Hemisphere of data
• collected. Space group P21/n, Nonius FAST
• But what is the reason for missing data
• inherent geometrical limitation?
• mistake in data collection or reduction?

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How does it work?
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Just being helpful ...
Alert A Given expected crystal density
differ Alert A Given expected absorption
coefficient differ Calculated density 3.377
density in CIF 1.689 Calculated mu 2.063
mu in CIF 1.031
Author Response It appears that the absmu- and
the density-problem are related. No explanation
other than it is related to the disordered
triflate groups and the refinement over several
partially occupied sites.
Cause of Alert Molecule sits over an inversion
centre in P21/n Z given as 4, instead of 2.
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How to get a CIF through

• Give ALL Alerts due consideration
• appreciate validation criteria
• criteria are based on normally expected results
  from routine analyses
• Why, then, is your structure not routine?

• In any VRF...
• avoid casual or circular responses
• show you understand the causes of the outlier
• explain why it is a true feature of the analysis

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What causes most problems?
VRN???01 Data completeness ALERT A probably
spurious PASSED VRN???02 Space group
ID is main subject of paper
PASSED VRN???03 Some H atoms mistreated -
authors to re-refine REJECT VRN???04 30
atoms isotropic in a very large structure
PASSED VRN???05 Coordinates/geometry mismatch
REJECT VRN???06 Max
shift/su gt 4.0
REJECT VRN???07 Perchlorate O atoms have
extreme ADPs PASSED VRN???08
Atom labels randomly scrambled
REJECT VRN???09 Extreme H U values -
inappropriate H atom treatment REJECT VRN???10
Not a connected set? - probably a false positive
PASSED VRN???11 Central heavy atoms have
high U wrt neighbors PASSED
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Common problems ...
VRN???12 VRN???06 again shifts now acceptable
PASSED VRN???13 H atom
treatment missing absorption correction
REJECT VRN???14 Solvent disorder modeling
high mean U3/U1 PASSED VRN???15
VRN???09 again still many problems with H atoms
REJECT VRN???16 VRN???09 again nearly there
PASSED VRN???17
Spurious warning (intensity standards) but AD
PASSED VRN???18 Ligands have geometric and
Ueq problems PASSED VRN???19
Problems with high U3/U1
PASSED VRN???20 Dataset only 65 complete
REJECT VRN???21
Completeness theta max was too high
PASSED VRN???22 Wide range of H-atom U
values very close H...H REJECT
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Common problems ...

• Data completeness or resolution too low

• Maltreatment of H atoms

• Structure not at convergence

• Missing or inadequate absorption correction

• Indications of a poor structure

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Acta C CIF submissions in 2000
Tony Linden (Zurich)
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Fate of CIFs with VRFs in 2000
2002 58 passed as is
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All Acta C submissions in 2000
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Validation is not a brick wall- either to run
into or get over -
97 of all submissions reach a Co-editor
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Myths and myth-understandings

• Introduction of validation
• Acta C electronic-only submission since 1996
• are validation criteria widely understood?
• explanations in Notes for Authors, etc

but a mythology has grown up...
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Myth 1 Acta will not consider problem or
difficult structures
Reality The problems or difficulties must be
explained and justified

• ? disorder ? twinning ? crystal size ?
  voids
• ? ADPs ? pseudosymmetry ? residual e-
• ? absorption ? H atoms

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Myth 2 Acta will not publish any structure
with R1 gt 0.05/0.07/0.10 ...
Scylla
Reality There is no formal cut-off, but a
structure with a high R1 will need to be
justified.
Abstract ... 2-(Di-n-propylamino)-8-hydroxytetrali
n (8OH-DPAT) hydrochloride, C16H26NO Cl-, M
283.8, monoclinic, P21/n, a 9.9587 (7), b
13.5746 (6), c 12.1558 (6) Å, ? 94.537 (6),
V 1638.1 Å3, Z 4, Dx 1.151g cm-3, ?(CuK?)
l.54184 Å, ? 19.00 cm-1, F(000) 616, T 298
K, final R 0.1781 with 1550 independent data.
The structure solution of 8OH-DPAT was hindered
by the poor quality of the one crystal obtained
...
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Myth 3 Acta will not publish a structure with
Z gt 1 where one of the molecules is disordered
Gorgon
Reality We welcome such interesting structures,
but the disorder must be treated adequately.
Acta Cryst. (1996). C52, 2814-2818 Two
C-Unsubstituted Enaminals Abstract In both
3-(N,N-diisopropylamino)-2-propenal, C9H17NO,
(3), and 3-(1,2,3,4-tetrahydro-l-quinolinyl)-2-pro
penal, C12H13NO, (4), the entire enaminal system
(O1C1C2C3N4) is approximately planar. The
angles around the N atoms in (3) and (4) sum to
values near 360 , indicating planarity in both
molecules. One of the two crystallographically
independent molecules of (3) exhibits disorder in
its isopropyl groups.
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Myth 4 Datasets must be (almost) perfectly
complete
Dragon
Reality A dataset need only be essentially
complete to 2? of ca. 50/Mo, and thereafter have
good completeness up to the diffraction limit.
_diffrn_reflns_theta_max 28.69
_diffrn_measured_fraction_theta_max 0.906
_diffrn_reflns_theta_full 26.00
_diffrn_measured_fraction_theta_full 1.000
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Myth or not?

• Is the assertion based on direct experience?

• Check with Notes for Authors (www.iucr.org)

• If in any doubt, ask a Co-editor (www.iucr.org)

• Your case may not be the same as a similar one

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checkCIF in 2004

• the new home of checkCIF http//checkcif.iucr.o
  rg
• service sponsored by ACS, CCDC and Elsevier
• an ORTEP plot is now included
• part of new Acta C/E submission procedures
• will soon have online upload of all material for
  Acta C and E papers (CIF figures/schemes/structu
  re factors)

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Validation and other Journals
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• Standards, procedures vary widely
• some journals perform extensive checks
• some do only very basic checks
• some do none at all
• ? so what do authors do ?

• Perform your own validation
• ensure there are no serious mistakes
• ensure the quality is adequate
• submit a copy of the checking report

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Example an ACS procedure

• Authors submit the CIF along with the paper
• CIF must contain author names and paper title
• authors must have checked the CIF first
• - the check report may be requested
• reviewers have Web access to the CIF, along with
  the manuscript and any supplementary data

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Other procedures

• Submit paper to journal
• get a code for the paper
• submit CIF under this code

• Submit CIF to CCDC or ICSD
• get deposition number
• include number in paper

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If you have a difficult structure

• Identify and describe the problem

• Give details of the remedial action taken

• Describe the (successful?) outcome

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Where and how?
1. Briefly in any experimental footnote

• At the top of the CIF
• use _refine_special_details

3. In any other Supplementary Data
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Example of text
_refine_special_details Disorder was identified
in one of the tetrafluoroborate anions. All the
F atoms were affected and two orientations were
identified.
Similarity restraints were applied to B-F
distances, and to F-B-F angles. All F atoms were
refined isotropically. The occupancies of each
group of four partially-occupied F atoms were
refined competitively using a free variable. Each
F atom was found to be disordered over two
equally occupied sites, as shown by the final
group occupancies of 0.506(12) and 0.494(12).
In the final model the range of B-F distances was
1.31(2)-1.42(2) Angstroms and the F-B-F angles
spanned 105(2)-112(2) degrees. No difference
Fourier peak in the region exceeds 0.6 e/A3.
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The limits of validation
(automatic validation will not catch every
problem)
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Possible limits to validation

• test not (yet) implemented
• test not practical
• error not a validation issue
• error cannot be detected from data in CIF
• nonsense entries in the CIF

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Test not implemented
Example High ADPs on isolated atom

• Not detected by
• rigid bond test
• atom type test
• ADP ratio test

Atom is probably O rather than Cl
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Test not practical
C-C range is 1.49 to 1.60 Å
However, C-C single bonds are found within this
range
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Error not a validation issue
_chemical_formula_sum 'C24 H12 Fe
O6' _exptl_crystal_description
needle _exptl_crystal_colour
colourless _exptl_crystal_size_max
0.28 _exptl_crystal_size_mid
0.24 _exptl_crystal_size_min 0.03
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Error not detectable from CIF data
Prior chemical information Complex is either
Ru/Ru or Ru/Zn
Refinement as Ru/Ru gave R1 0.064 unusual
five-coordinate Ru geometry
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Difference map with Ru/Ru model (R1 0.064)
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Difference map with Zn/Zn model (R1 0.022)
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Other examples
Ag?CN?Ag link, Ag?NC?Ag link or disordered?
could only be resolved using ?F maps
M. Schröder (Nottingham)
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Model complexes for NiFe hydrogenase
need good data to distinguish Ni and Fe by
refinement Ni (Z 28) vs Fe (Z 26) ?Z/Z 2/28
R1 lt 4 ?Z ?
M. Schröder (Nottingham)
Use ?F maps to confirm and when data are poor
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Lanthanide complexes
Ln Er, Tm or Yb ?
Z 68, 69, 70
Similar co-ordination
Similar geometry parameters
Crystallography is not much good at
distinguishing these metals
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Nonsense entries in the CIF
_diffrn_ambient_temperature 293(2)
_diffrn_radiation_wavelength
0.69010 _diffrn_radiation_type
synchrotron _diffrn_radiation_source 'fine-focus
sealed tube' _diffrn_radiation_monochromator
'graphite' _diffrn_measurement_device_type
'SMART 1k on Daresbury SRS Station 9.8'
see W. Clegg, Acta Cryst. 2003, E59, e2-e5
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Unsuitable SHELX(T)L-97 defaults ?

• space group notation
• diffractometer
• T 293 K ?
• absorption correction
• total data collected
• index limits

• Rint
• H atom treatment
• weighting scheme
• precision
• structure solution

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SUMMARY
1. Overview of validation and checking
2. Validation for IUCr journals
3. Validation for chemical journals
4. The limits of validation
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Thanks to
..... ..... George Ferguson Ton Spek Peter
Strickland ..... ..... .....