The System-S Approach to Automated Structure Determination: Problems and Solutions

1. The System-S Approach to Automated Structure Determination:Problems and Solutions Ton Spek National Single Crystal Service Utrecht University, The Netherlands

2. Is a Fully Automatic Structure Determination Possible ? • Yes, in many cases given good quality low temperature reflection data and correct prior knowledge of the chemical composition. • Good examples are light atom structures with no disorder and with no unknown solvent of crystallization. • No, in all cases needing an experienced crystallographer (I.e. when no automated methods are available yet for the problem at hand) e.g.: many/most coordination complexes.

3. Current Setup in Utrecht KappaCCD/Rotating Anode/LNT I Collect, DENZO or EVAL-CCD (Not AUTO!) I import.cif (includes Formula & Unit Cell) I Silent System-S Auto-Mode: platon -F import.cif I Result files -> ORTEP/PLUTON Plots

4. Typical Import CIF Filter Job Unix Command Line Instruction: platon –F import.cif ….. Wait 0.5 minute ….. Standard Console Output: Tentative Result on: /mnt/spea/import_s.cif and: /mnt/spea/import_s.res Validation Report: /mnt/spea/import_s.chk Details may be found in: /mnt/s/import

5. 0.5 Min. from import.cif to ORTEP (3GHz Linux Box)

6. System-S Approach • Crystallographic Shell around public domain tools (SHELX, SIR, PLATON etc.) • Two Modes of operation: • Guided Mode: Suggests/Executes next step in the structure determination (handles I/O) • Automatic Mode: (NQA-Mode) Executes automatically all default steps • Build-in Structure Validation • System-S is included in the UNIX PLATON exe.

7. Standard System-S Example • Two files: name.ins & name.hkl • Content name.hkl : SHELX style HKLF 3/4 • Content name.ins: TITL, CELL, CELLSD, SFAC, UNIT, HKLF 4 (or 3) • Note: No Spacegroup Info Needed • Run: s name.ins NQA. • 18 Seconds later for C16H20NO3P ….

9. Problems and Solutions • There are still many interesting ‘Real World’ problems to be solved for a full proof automatic replacement of an experienced crystallographer. • Already the use of the Guided Mode to quickly try multiple approaches to solve a structure is a big help (even for the experienced crystallographer) • System-S stores all relevant I/O files in a hierarchic directory structure for inspection when problems arise.

10. Problem #0 – Complete Failure • Example: The chemist provides us with crystals labeled to be a Zn-coordinationcomplex requiring human ‘Expert Forensic Crystallography’ to tell us that the inorganic salt MnK2(SO4)2 gives us a perfect fit with the experimental data. Partial Solution: Check with databases (I.e. CELL or simulated powder patterns) and stop.

11. Failure #1 – Space group • The space group can not always be determined uniquely from systematic absences (e.g Cc or C2/c). • Some structures solve only in lower than the actual space group symmetry (sometimes only in P1) • Solution: loop over the various space group candidates to solve the structure and use ADDSYM to find out about the correct symmetry of the model (implemented in S).

12. Failure #2 – Phase Problem • Attempts to automatically solve a structure with a single solution package might fail. • Solution: loop over all available packages and approaches until a solution is found. • System-S: SHELX86, SHELXS97, SHELXD, SIR97, SIR2002, DIRDIF99 • ‘Workup’ with EXOR – Example next …

13. Raw Output from SHELXS86

14. Result of the EXOR workup

15. Failure #3 – Incorrect Atom Type Assignment • Automatic atom type assignment is not always straightforward. • A large variation in displacement parameters often hampers a correct atom type assignment • Solution: detailed analysis of intra- and intermolecular geometry and ADP’s • Example next …

16. Misassigned Atom Types (S & P)

17. Atom Type Assignment Assignment Methods (can be) based on: 1 - An analysis of the Peak heights & Shapes 2 - the value of the displacement parameters 3 - Population parameter refinement (S) 4 - Refinement of each site with alternative scattering types (E.g. C,N,O) 5 - Chemistry (& CSD knowledge, Mogul)

18. Failure #4 - Disorder • Type 1 – Orientational, Conformational or Substitutional disorder of (part of) the structure. Solution: (Expert) Crystallographer • Type 2 – Voids filled with unknown (mixtures of) solvents. Solution: PLATON/SQUEEZE

19. Failure #5 - Twinning • (Pseudo) Merohedral Twinning may lead to refined structures with unexpectedly high final R-values and high residual peaks in a difference Fourier Map. • Solution: Software to detect the applicable twin law. E.g. Rotax (Simon Parsons & Bob Gould) available in WINGX and CRYSTALS or PLATON/TwinRotMat Example next ….

20. 3 independent molecules Space group P-3 – R = 20 %

23. Problem #6 – Wrong Structure • Sometimes automatic procedures can come up with ‘reasonably looking’ but wrong structures. • Structure validation software should send out proper ALERTS (e.g. IUCr Checkcif) • Example: The chemist expects a Cu-complex, so that is what he gets … (confirmed by X-raycrystallography !) …. and tries to publish … and caught by a knowledgeable referee … on the bases of Checkcif ALERTS.

24. R < 7 % Cu not Coordinated => ORTEP of the False Structure

25. R < 6 % Ortep of the Correct Structure

26. CONCLUDING REMARKS • SYSTEM-S can be used easily for the re-examination of structures with CIF + FCF data taken from the Acta Cryst Archives or for refereeing purposes to investigate unclear details of the analysis. • Future implementation: C,N,O etc. discrimination in difficult cases More chemical knowledge Extension of the already available procedures for structure determination without any Content Information.

27. End