Validation and checking
of 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
How do we know
whether this structure
is correct and reliable?
G. Pattenden (Nottingham)
OUTLINE
• Overview validation and checking
• Validation for Acta C, etc
 Myths and misunderstandings
• Validation for other journals
• The limits of validation
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
Valid-ation
Correct
Appropriate
Defensible
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?
Automated data validation with
checkCIF or PLATON
• Checks for
– CIF construction and syntax errors
– missing information
– parameters outside expected norms
– conformation with convention
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 > 1.30
An absorption correction is required.
Alert A Atom C58A
ADP max/min Ratio
18.00
ALERT LEVELS
B
Significant – action needed?
Item is a significant or unexpected outlier
Alert B The formula has elements in wrong order
Alert B ADDSYM detects Cc to Fdd2 transformation
Alert B Refined extinction parameter < 1.9s
Alert B Structure contains VOIDS of 130.00 Å3
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 given
Alert C Short inter X...Y contact: O7...C1 = 2.96 Å

Alert C Low U(eq) as compared to neighbors:
C1
Alert C D-H without acceptor N2–H2
?
C1 and N2 should be N and C, respectively
ALERT LEVELS
G General issues – check
ALERT_3_G
The ratio of expected to reported Tmax/Tmin (RR') is < 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 .. XHn:H19B .. H30A = 1.81 Ang.
720 ALERT 4 C Number of Unusual/Non-Standard Label(s) .... 1
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
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!!
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?
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
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
A pretty picture, but what
about the numbers …
1.369 Å
1.441 Å
1.390 Å
1.897 Å
Br
… in fact the bond
lengths match the
values expected
P.J. Cox, RGU, Aberdeen
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
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
Validation and IUCr Journals
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
Early 1990’s - 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 
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
Crystal growth
Data collection
Refinement
Structure analysis
Prepare CIF
Submit to CHECKCIF
Alerts present
Alerts not present
Resolve alerts
Submit to Chester
Submission
processed normally
Authors
working
with
CHECKCIF
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)
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 !
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.
An inadequate answer
Alert A
< 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?
How does it work?
Best effort
at resolving
A, B & C alerts
A alerts
still present
No
A Alerts
Outliers
not justifiable
Sound reasons
for outliers
Submit CIF
to Chester
Re-evaluate
project
Include VRF
& submit
Processed
normally
Validation Editor
Disagrees
Approves
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.
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
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 > 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
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
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
Acta C CIF submissions in 2000
20% with
VRF
Tony Linden (Zurich)
80% valid
Fate of CIFs with VRFs in 2000
16% not
resubmitted
48%
passed
as is
16%
passed on
next try
20%
returned
as valid
2002: 58% passed as is
All Acta C submissions in 2000
7% valid
after
revision
3% not
resubmitted
10% with
valid VRF
80% valid
Validation is not a brick wall
- either to run into or get over -
97% of all submissions reach a Co-editor
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...
Myth 1:
“Acta will not consider ‘problem’ or
‘difficult’ structures”
Reality: The problems or difficulties must be
explained and justified
 disorder
 ADPs
 twinning
 crystal size
 pseudosymmetry
 absorption
 H atoms
 voids
 residual e-
Myth 2: “Acta will not publish any
Scylla
structure with R1 > 0.05/0.07/0.10 ...”
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-hydroxytetralin (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 ...
Myth 3: “Acta will not publish a
Gorgon
structure with Z’ > 1 where one of
the molecules is disordered”
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-(1,2,3,4tetrahydro-l-quinolinyl)-2-propenal, C12H13NO, (4), the entire enaminal system (O1–
C1–C2–C3–N4) 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.
Myth 4:
Dragon
“Datasets must be (almost) perfectly
complete”
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
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
checkCIF in 2004
• the new home of checkCIF:
http://checkcif.iucr.org
• 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/structure factors)
Validation and other Journals
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
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
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
If you have a “difficult” structure
• Identify and describe the problem
• Give details of the remedial action taken
• Describe the (successful?) outcome
Where and how?
1. Briefly in any experimental footnote
2. At the top of the CIF
use _refine_special_details
3. In any other Supplementary Data
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/A**3.
;
The limits of validation
(automatic validation will not catch every problem)
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
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
Test not practical
C-C range is 1.49 to 1.60 Å
However, C-C single
bonds are found within
this range
Error not a validation issue
_chemical_formula_sum
_exptl_crystal_description
'C24 H12 Fe O6'
needle
_exptl_crystal_colour
colourless
_exptl_crystal_size_max
0.28
_exptl_crystal_size_mid
0.24
_exptl_crystal_size_min
0.03
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 fivecoordinate Ru geometry
Difference map with Ru/Ru model (R1 = 0.064)
Difference map with Zn/Zn model (R1 = 0.022)
Other examples
AgCNAg link,
AgNCAg link
or disordered?
could only be
resolved
using F maps
M. Schröder (Nottingham)
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 < 4 Z ?
Use F maps to confirm
and when data are poor
M. Schröder (Nottingham)
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
Nonsense entries in the CIF
_diffrn_ambient_temperature
293(2)
_diffrn_radiation_wavelength
_diffrn_radiation_type
*
0.69010
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
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
SUMMARY
1. Overview of validation and checking
2. Validation for IUCr journals
3. Validation for chemical journals
4. The limits of validation
Thanks to
..... .....
George Ferguson
Ton Spek
Peter Strickland
..... ..... .....