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

G. Pattenden (Nottingham)

How do we know whether this structure is correct and reliable?

• 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

Valid-ation

Correct

Appropriate

Defensible

• 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

outlierAlert B The formula has elements in wrong orderAlert B ADDSYM detects Cc to Fdd2 transformationAlert B Refined extinction parameter < 1.9sAlert 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 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 N2–H2 ?

C1 and N2 should be N and C, respectively

ALERT LEVELS

G General issues – checkALERT_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

A pretty picture, but what about the numbers …

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 PLATON2. Augment CIF using e.g. XCIF and enCIFer3. Re-check the CIF using PLATON or checkCIF4. Look at ellipsoid plots from several directions5. Check bond lengths are sensible and

consistent6. After any changes, re-check the CIF

VALIDATION/CHECKING PROCEDURE

Validation and IUCr Journals

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 Cheste r

A lerts no t presen t

Submit to CHECKCIF

Prepare C IF

Crystal growthData co llection

RefinementStructure 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 Editor

Include VRF& subm it

Sound reasonsfor ou tliers

A alertsstill presen t

P rocessednormally

Submit C IFto Cheste r

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 differAlert A Given & expected absorption coefficient differCalculated density = 3.377 density in CIF = 1.689Calculated 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

Acta C CIF submissions in 2000

20% with VRF

80% validTony Linden (Zurich)

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)

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 journalget a code for the papersubmit CIF under this code

• Submit CIF to CCDC or ICSDget deposition numberinclude 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 CIFuse _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.;

(automatic validation will not catch every problem)

The limits of 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

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

Difference map with Ru/Ru model (R1 = 0.064)

Difference map with Zn/Zn model (R1 = 0.022)

AgCNAg link, AgNCAg linkor disordered?

could only be resolved

using F mapsM. Schröder (Nottingham)

Other examples

need good data to distinguish Ni and Fe by

refinementNi (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

Thanks to

..... ..... George Ferguson

Ton SpekPeter Strickland

..... ..... .....