An Update on Current and New Structure Analysis Tools in PLATON Ton Spek, Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands. ACA, Boston, Aug 1, 2012 Without Dikes Utrecht on Sea

PLATON – Updates – Similar to dikes, software requires maintenance to keep up with current scientific needs, new insights and changing standards – PLATON is a container of multiple software tools for chemical crystallography – The program is continuously updated to keep up with: – Our own research needs – Ideas, bug reports and comments of users – The IUCr CheckCIF project – Many current changes are related to the anounced new SHELXL2012 and SHELXT tools

f' and f'' and mu values – SHELXL and XL include (for all atom types) proper values for f', f'' and mu exclusively for the three wavelengths CuKa, MoKa and AgKa – Resonance values for other wavelengths (synchrotron) have to be added manually with DISP and SFAC records in the.ins. Also the wavelength should be given with its actual value. If not, CheckCIF will generate associated ALERTS – PLATON calculates suitable values following Brennan & Cowan (1962) – Available instruction: ANOM wavelength (element)

Resonance Scattering data calculated with PLATON for lambda = 1.8 Angstrom (following Brennan & Cowan)

CIF & FCF-Validation The SHELXL-2012 CIF will include the final.res and.hkl for additional documentation and future use, and implicitly includes info on twinning, constraint & restraint details. FCF-Validation is now a standard part of the IUCr CheckCIF service. A listing file is created with a report on various issues: - Variance analysis (similar to SHELXL) – next example - Data set completeness beamstop reflections and outliers - Checks for unresolved twinning (TwinRotMat) - Checks on the value of the Flack parameter (Hooft y) - Residual density – including density on atom sites

Analysis Of Variance section

The Disordered Solvent Problem Molecules of interest often co-crystallize (only) with the inclusion of a suitable solvent molecule in the lattice. Solvent molecules often fill voids in a structure with little interaction with the main molecule (disorder) and are often located on symmetry sites and with population less than 1.0 Sometimes even the nature of the (mixture) of included solvent(s) is unclear. Refinement of a meaningful disorder model is preferable in cases of understood disorder (e.g. toluene disordered over an inversion centre) Refinement of cases of hopeless solvent disorder can be handled with the SQUEEZE method. The ordered part of the structure should have no unresolved issues and the data should be essentially complete to sin(theta/lambda) = 0.6. There should be no charge balance problem.

SQUEEZE Takes the contribution of disordered solvents to the calculated structure factors into account by back-Fourier transformation of density found in the ‘solvent accessible volume’ outside the ordered part of the structure (iterated). Prototype and proof of principle implementation named BYPASS around the SHELX76 refinement tool. [P. van der Sluis & A.L. Spek, (1990). Acta Cryst. A46, ] Current implementation as PLATON/SQUEEZE around the SHELXL97 refinement tool. (Involving the solvent free.hkl file workaround, no proper twin handling) Soon: SHELXL2012 now accepts fixed A & B contributions of the solvent to the structure factor calculations thus eliminating the ‘solvent free’.hkl step. The new SHELXL2012 ‘LIST 8’ detwinned.fcf file will now allow the application of SQUEEZE for twins as well.

THE MOLECULE THAT INVOKED THE BYPASS/SQUEEZE TOOL Salazopyrin from DMF – R = 0.096

Structure Modelling and Refinement Problem for the Salazopyrin Structure Difference Fourier map shows channels with continuous density rather than maxima How to handle and model this in the Refinement ? Our solution: SQUEEZE !

Looking down the Infinite Channels in the Salazopyrin Structure The Problem: Peak Search algorithms will not always tell about the residual density. We need special tools to detect voids in a modeled structure.

FIRST STEP OF SQUEEZE: LOCATE SOLVENT ACCESSIBLE VOID The Black areas indicate discrete model atom with van der Waals radii assigned. The white area is the solvent accessible volume

I Informal Theory of the SQUEEZE Procedure M = Ordered S = Solvent Solvent Free ElectronCount Iterate (Initially

SQUEEZE In the Complex Plane Trick needed to refine with SHELXL97 Fc(model) Fc(solvent) Fc(total) Fobs Solvent Free Fobs Black: Split Fc into a discrete and solvent contribution Red: For SHELX97 refinement, temporarily substract the recovered solvent contribution from Fobs. (Reinstated after convergence)

SQUEEZE Procedure with SHELXL97 In this mode, the solvent contribution to the observed data is temporarily removed during the SHELXL refinement. 1 – Standard name.ins/res name.hkl refinement to convergence: shelxl name 2 – Run PLATON/SQUEEZE as platon -q name.res with relevant results on name-sr.ins (= name.res), name-sr.hkl (= solvent free Fobs), name-sr.sqf (= CIF info) & name.lis Note: This is difference map iteration and not refinement 3 – Continue refinement to completion: shelxl name-sr 4 – Run PLATON as platon name-sr.res with the CalcFCF-sq menu tool to create a final CIF & FCF (that again includes the original I(obs))

SQUEEZE Procedure with SHELXL – Refine ordered model with name.ins (+ ACTA) and name.hkl as: shelxl2012 name to convergence => name.cif & name.fcf 2 – Run SQUEEZE as: platon -q name.cif. The relevant output files are name.lis, name_shelxl.ins (= name.res), name_shelxl.hkl (= name.hkl), name_shelxl.fab & name- sr.sqf. 3 – ADD the instruction 'ABIN' to name_shelxl.ins 4 – Refine as shelxl2012 name_shelxl (in the presence of name_shelxl_ins, name_shelxl.hkl & name_shelxl.fab) 5 – Append the 'name-sr.sqf' file to the final name_shelxl.cif to archive the details of the SQUEEZE run In this more elegant mode, the observed Fobs data remain untouched

Refined structure without disordered solvent (THF) contribution R = 0.067, wR2 = 0.236, S = Rho(min) = -0.49, Rho(max) = 3.96 Refined structure (with SHELXL2012) After SQUEEZE R = 0.030, wR2 = 0.076, S = Rho(min) = -0.35, Rho(max) = 0.48

SQUEEZE Procedure with SHELXL2012 and Twinning The SQUEEZE algorithm is based on the analysis of an untwinned difference map. SHELXL2012 can produce a 'type 8' style.fcf with detwinned data. This will provide a pathway to apply SQUEEZE to twinned structures However it is likely that the detwinning operation has to be recycled There is no experience yet

Thanks ! Thanks to all who have send me bug reports and useful suggestions And George Sheldrick for the new SHELX(T/2012) PLATON runs from a terminal window under LINUX and MAC-OSX And MS-Windows + Louis Farrugia MS-Windows GUI