Platon, a set of Tools for the Interpretation of Structural Results Ton Spek National Single Crystal Service Facility

PLATON, A set of Tools for the Interpretation of Structural Results

• Ton Spek

• National Single Crystal Service Facility,

• Utrecht University,The Netherlands

• ACA2007, July 23, 2007

What is PLATON

• PLATON is a collection of tools for single crystal structure analysis bundled within a single SHELX compatible program.

• The tools are either extended versions of existing tools or unique to the program.

• The program was/is developed in the context of our national single crystal service facility in the Netherlands.

PLATON USAGE

• Today, PLATON is most widely used implicitly in its validation incarnation for all single crystal structures that are validated with the IUCr CHECKCIF utility.

• Tools are available in PLATON to analyze and solve the reported issues that need attention.

• PLATON also offers automatic structure determination and refinement tools for routine structure analyses from scratch (i.e. the ‘Unix-only’ SYSTEM S tool and the new STRUCTURE tool that is based on the Charge Flipping Ab initio phasing method).

• Next Slide: Main Function Menu 

Selected Tools

• ADDSYM – Detect and Handle Missed Symmetry

• TwinRotMat – Detection of Twinning

• SOLV - Solvent Accessible Voids

• SQUEEZE – Handling of Disordered Solvents in Least Squares Refinement

• BijvoetPair – Absolute Structure Determination

ADDSYM

• Often, a structure solves only in a space group with lower symmetry than the correct space group. The structure should subsequently be checked for higher symmetry.

• About 1% of the 2006 & 2007 entries in the CSD need a change og space group.

• E.g. A structure solves only in P1. ADDSYM is a tool to come up with the proper space group and to carry out the transformation

• Next slide: Recent example of missed symmetry

Things to be Checked

• Consistency of the new cell parameters with the new crystal system

• New systematic absences

• Pseudo-symmetry

• Analyse potential disorder

• Successful re-refinement

(Pseudo)Merohedral Twinning

• Options to handle twinning in L.S. refinement available in SHELXL, CRYSTALS etc.

• Problem: Determination of the Twin Law that is in effect.

• Partial solution: coset decomposition, try all possibilities

• (I.e. all symmetry operations of the lattice but not of the structure)

• ROTAX (S.Parson et al. (2002) J. Appl. Cryst., 35, 168.

• (Based on the analysis of poorly fitting reflections of the type F(obs) >> F(calc) )

• TwinRotMat Automatic Twinning Analysis as implemented in PLATON (Based on a similar analysis but implemented differently)

TwinRotMat Example

• Structure refined to R= 20% in the trigonal space group P-3.

• Run TwinRotMat on CIF/FCF

• Result: Twinlaw with an the estimate of the twinning fraction and the estimated drop in R-value

• Example of a Merohedral Twin 

Ideas behind the Algorithm

• Reflections effected by twinning show-up in the least-squares refinement with F(obs) >> F(calc)

• Overlapping reflections necessarily have the same Ɵ within a tolerance.

• Statistical analysis of possible twin axes

Possible Twin Axis

Solvent Accessible Voids

• A typical crystal structure has only 65% of the available space filled.

• The remainder volume is in voids (cusps) in-between atoms (too small to accommodate an H-atom)

• Solvent accessible voids can be defined as regions in the structure that can accommodate at least a sphere with radius 1.2 Angstrom without intersecting with any of the van der Waals spheres assigned to each atom in the structure.

• Next Slide: Void Algorithm: Cartoon Style 

VOID APPLICATIONS

• Calculation of Kitaigorodskii Packing Index

• As part of the SQUEEZE routine to handle the contribution of disordered solvents in crystal structure refinement

• Determination of the available space in solid state reactions (Ohashi)

• Determination of pore volumes, pore shapes and migration paths in microporous crystals

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).

• Filter: Input shelxl.res & shelxl.hkl

• Output: ‘solvent free’ shelxl.hkl

• Refine with SHELXL or Crystals

SQUEEZE Algorithm

• Calculate difference map (FFT)

• Use the VOID-map as a mask on the FFT-map to set all density outside the VOID’s to zero.

• FFT-1 this masked Difference map -> contribution of the disordered solvent to the structure factors

• Calculate an improved difference map with F(obs) phases based on F(calc) including the recovered solvent contribution and F(calc) without the solvent contribution.

• Recycle to 2 until convergence.

Comment

• The Void-map can also be used to count the number of electrons in the masked volume.

• A complete dataset is required for this feature.

• Ideally, the solvent contribution is taken into account as a fixed contribution in the Structure Factor calculation (CRYSTALS) otherwise it is substracted temporarily from F(obs)^2 (SHELXL) and reinstated afterwards for the final Fo/Fc list.

Publication Note

• Always give the details of the use of SQUEEZE in the comment section

• Append the small CIF file produced by PLATON to the main CIF

• Use essentially complete data sets with sufficient resolution only.

• Make sure that there is no unresolved charge balance problem.

Absolute Structure Determination

• Generally done as part of the least squares refinement with a ‘twinning’ parameter.

• Determine Flack parameter + su

• Analysis following the Flack & Bernardinelli criteria.

• Often indeterminate conclusions in the case of light atom structures

• Alternative approaches offered by PLATON 

Scatter Plot of Bijvoet Differences

• Plot of the Observed Bijvoet Differences against the Calculated Differences.

• A Least-Squares line and Correlation Coefficient are calculated

• The Least-squares line should run from the lower left to to upper right corner for the correct enantiomorph and the Correlation close to 1.0

Practical Aspects of Flack x

• The structure should contain atoms with sufficiently strong anomalous dispersion contributions for the radiation used (generally in the experiment (e.g. Br).

• Preferably, but not nesessarily, a full set of Friedel pairs is needed. (correlation !)

• Unfortunately, many relevant pharmaceuticals contain in their native form only light atoms that at best have only weak anomalous scattering power and thus fail the strict Flack conditions.

Light Atom Targets

• Options for the Absolute Structure Determination of Light Atom Compounds

• Add HBr in case of tertiary N.

• Co-crystallize with e.g. CBr4.

• Co-crystallize with compound with known. absolute configuration.

• Alternative: Statistical analysis of Bijvoet pair differences.

Statistical Analysis of Bijvoet Pairs

• Many experimentalists have the feeling that the official Flack x method is too conservative.

• Experience based on multiple carefully executed experiments with compounds with known absolute structure.

• The feeling is that also in light atom structures the average of thousands of small Bijvoet differences will point in the direction of the correct enantiomorph.

• Example: The Nonius CAD4 test crystal 

Bayesian Approach

• Rob Hooft has developed an alternative approach for the analyses of Bijvoet differences that is based on Bayesian statistics. Details will be discussed in the lecture of Rob Hooft.

• Under the assumption that the material is enantiopure, the probability that the assumed absolute structure is correct, given the set of observed Bijvoet Pair Differences, is calculated.

• An extension of the method also offers the Fleq y parameter to be compared with the Flack x.

• Example: Ascorbic Acid, MoKa data 

Proper Procedure

• Collect data with an essentially complete set of Bijvoet Pairs

• Refine in the usual way with BASF and TWIN instructions (SHELXL)

• Invoke PLATON with the final .cif and .fcf files

• Bijvoet Pair differences will be recalculated by PLATON with the parameters in the CIF excluding the Flack Parameter.

END

• THANK YOU

• More info

• http://www.cryst.chem.uu.nl

• Including this ppp