validation and checking of crystal structures this presentation contains material from the following...
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Validation and checkingof crystal structures
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
Alexander J. Blake, University of Nottingham, UKand
Anthony Linden, University of Zurich, Switzerland
• Overview validation and checking
• Validation for Acta C, etc
Myths and misunderstandings
• Validation for other journals
• The limits of validation
OUTLINE
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
• Does the structure make sense to you?
• Does the structure look right?
• Do chemically equivalent bonds agree?
• Are all CIF entries complete and correct?
Checking is additional to validation
Automated data validation with checkCIF or PLATON
• Checks for
– CIF construction and syntax errors
– missing information
– parameters outside expected norms
– conformation with convention
A Serious – attention essentialItem omitted or large deviation from
norm
Alert A No crystal dimensions have been given
Alert A Ratio of Tmax/Tmin expected is > 1.30An 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
ALERT LEVELS
C Outside expected norms – examineMay 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 .... C18412 ALERT 2 C Short Intra XH3 .. XHn:H19B .. H30A = 1.81 Ang.720 ALERT 4 C Number of Unusual/Non-Standard Label(s) .... 1
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
A/B/C indicate the seriousness of the problem
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
A visual examination can often be revealing: here there are some extreme ellipsoids which are also incompatible with a rigid bond model
Looking at the structure
1.897 Å
Br
1.390 Å
1.441 Å1.369 Å
P.J. Cox, RGU, Aberdeen
… in fact the bond lengths match the values expected
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
Less satisfactory
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/CHECKING PROCEDURE
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
Pre-electronic times
• 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
Early 1990’s - CIF introduced
• 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
Automation of syntax and data checks
Authors working
with CHECKCIF
Resolve alerts
A lerts p resent
Submissionprocessed normally
Submit to Chester
A lerts no t present
Submit to CHECKCIF
Prepare C IF
Crystal growthData co llection
RefinementS tructure analysis
• is there a soundsound scientificscientific basisbasis 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)
If you still get A alerts
• 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 !
Assessment of VRF
A valid riposte
Alert BADDSYM detects additional (pseudo) symmetry element: I
Author Response:This additional symmetry element doesnot 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?
Re-evaluateprojec t
Outliersnot justifiable
D isagrees Approves
Validation Edito r
Include VRF& subm it
Sound reasonsfor ou tliers
A alertsstill present
Processednormally
Subm it C IFto Chester
NoA A lerts
Best effortat resolving
A, B & C alerts
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.
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
Cause of Alert: Molecule sits over an inversion centre in P21/n: Z given as 4, instead of 2.
• 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?
How to get a CIF through
• 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
Fate of CIFs with VRFs in 2000
48% passed
as is
20% returnedas valid
16% passed on
next try
16% not resubmitted
2002: 58% passed as is
All Acta C submissions in 2000
3% not resubmitted
10% with valid VRF
80% valid
7% valid after
revision
97% of all submissions reach a Co-editor
Validation is not a brick wall
- either to run into or get over -
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...
Myths and myth-understandings
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
Scylla
Myth 2: “Acta will not publish any
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 ...
Gorgon
Myth 3: “Acta will not publish a 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-(1,2,3,4-tetrahydro-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: “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.
Dragon
_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)
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
1. Briefly in any experimental footnote
Where and how?
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.;
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
Possible limits to validation
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 '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
Prior chemical information: Complex is either Ru/Ru or Ru/Zn
Refinement as Ru/Ru gave R1 = 0.064; unusual five-coordinate Ru geometry
Error not detectable from CIF data
AgCNAg link,
AgNCAg link
or disordered?
could only be resolved
using F mapsM. Schröder (Nottingham)
Other examples
need good data to distinguish Ni and Fe by
refinement
Ni (Z = 28) vs Fe (Z = 26)
Z/Z = 2/28
M. Schröder (Nottingham)
R1 < 4 Z ?
Model complexes for [NiFe] hydrogenase
Use F maps to confirm and when data are poor
Lanthanide complexes
Ln = Er, Tm or Yb ?
Z = 68, 69, 70
Similar geometry parameters
Similar co-ordination
Crystallography is not much good at distinguishing these metals
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
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