1. Structure Solution and Basic Refinement

2. Recommended software Shelx WinGX Platon Solution programs (see later)
WinGX
Platon
Solution programs (see later)
A good text editor
e.g. Notepad++

3. Chemistry Facilities
Bruker Smart Apex CCD Diffractometer

4. Chemistry Facilities

5. From crystal to cif Get crystal Short experiment to index
Long experiment to collect complete data
Integration
Absorption correction
Identify space group
Solve  You start here
Refine
Cif

6. What is crystallography all about
A crystal is a 3D periodic array of molecules
X-rays interact with (diffract from) electrons
Diffraction results in a regular pattern of spots (due to constructive and destructive interference)
Intensities observed are related to atom types and positions
We build a model and compare the calculated diffraction pattern with the observed

7. The experiment

8. What you will get from us
2 or 3 files
ins file
The shelx instruction file contains unit cell, radiation wavelength, temperature, crystal system and space group information, unit cell contents from user input
hkl file
The reflection data, contains indexed intensities with associated estimated standard deviations
cif file
Contains some experimental details (not essential)

9. Files – ins file TITL pg24 in P-1
CELL
ZERR
LATT 1
SFAC C H N S HG
UNIT
PATT
HKLF 4
END

10. Files – hkl file

11. Structure Solution We need to get an initial model from which to work
This is called structure solution
We can only measure intensity but we really want to know the phase of each reflection.
Several methods of extracting initial estimated phases from our data are available.

12. Structure solution Direct methods Requirements How it works
It is desirable but not required to have a centrosymmetric structure.
How it works
Uses statistical relationships between the intensity of different reflections to establish phases.
Look out for…
This is a very powerful method which often works very well but as it is based on statistical analysis, it will sometimes fail.
Computationally demanding. Scales inversely with symmetry, i.e. low symmetry large unit cells take more time.

13. Structure solution Direct Methods Programs
xs from the shelx suite (works for me 99% of the time)
Instruction is TREF
You may specify a number after TREF to increase the number of trials for difficult structures.
Sir software
Several versions
Sir92, Sir97, Sir2002, Sir2004
May get different results with different versions
Variety of options for structures of different size/difficulty OR
Can be set up through, e.g. WinGX for simplicity but less control.

14. Structure solution Patterson Methods Requirements How it works
A heavy element, e.g. Fe, Cl, S, etc
How it works
Generates a map of ‘peaks’ representing difference vectors, i.e. interatomic vectors
Peak intensity is related to the product of the atomic numbers of the two atoms involved thus the heaviest elements are identifiable.
Look out for…
Depending on the program you may only get the heavy atom positions. Completing the structure may take more time and effort than e.g. Direct methods

15. Structure Solution Patterson Methods Programs xs from the shelx suite
Instruction is PATT
You will only get heavy atom positions back
Dirdif
Will attempt to complete the model and guess atomic assignments.
Can be extremely useful for complicated metal clusters, etc.

16. Structure Solution Partial Structure Expansion Requirements
Knowledge of expected substructures and their geometries, e.g. a benzene ring
How it works
Uses a Patterson map and rotates the substructure around three axes until a best fit is found to the data. There will then be attempts to complete the model using the phase information from your partial structure as a basis for phase refinement.
Look out for
Not many pitfalls assuming you are confident of the unit cell contents.
More time consuming to set up than other methods and unsuitable for unknown samples.

17. Structure Solution Partial structure expansion programs
PATSEE from the wingx suite
You must provide a list of coordinates for your substructure.
Dirdif
Provides a small database of common geometries e.g. benzene rings, indoles or can use your own.
Not necessarily user friendly in my opinion

18. Structure solution Charge flipping Requirements How it works
Complete data (at the moment)
How it works
Use random phases, ‘flip’ the sign of electron density charge below a threshold and get new phases. Use new phases with original magnitudes. Repeat.
No symmetry is used for solution. It is determined afterwards.
Look out for…
Unreliable results with incomplete data

19. Structure solution Charge-flipping software Superflip Flipper
From originators of the method
Available as standalone (not recommended), via WinGX, via crystals
Flipper
Available in Platon

20. Structure solution Has it solved? Use your chemical knowledge…
How atoms interact
E.g. expected bond distances and angles for particular arrangements
Reactions or decompositions which may occur
Non-bonded interaction lengths and types
E.g. +ve to +ve is not going to be common
Charge
Should always be neutral for a unit cell
Assignment of charge on metals, ligands
Likely patterns of motion
E.g. neighbouring atoms are likely to have similar thermal motion
Spinning or wagging of certain groups may be expected
Groups which are likely to be rigid, move as one

21. Structure solution Watch out for…
If provided, don’t assume atomic assignments are correct.
Look for expected geometry, e.g. rings, octahedra
Might get messy q-peaks and need to trim back to your structure.
Don’t assume that if you can’t see your compound that is isn’t there and just obscured by noisy peaks
Incorrect atomic assignment and missing atoms will affect the calculated phases and may mean some atoms don’t appear at first.
Be patient
Try any and all structure solution programs you can find
Different programs produce different results even using the same method.
Those mentioned are not the only ones but should be sufficient.

22. Structure Solution example
Data taken from Oxford primer:
Crystal structure determination
William Clegg

23. Refinement Iterative process Be patient
Sometimes it takes a long time and is difficult
Sometimes it is easy and quick
You must model all electron density (q-peaks) or be able to explain why modelling some peaks is not appropriate.
Structure must be chemically reasonable
Pay attention to
Geometry
R-factors
Q-peaks
ADP’s
Contacts

24. Typical Refinement START Switch current atoms to anisotropic No
All atoms
anisotropic?
Yes
Weighting
scheme
converged
FINISH!
Initial solution
None
not converged
All atoms correctly identified?
Yes
Model
complete?
Yes
Refine… Problems?
yes
Large
Q-Peaks
Missed
Atoms?
yes No No
Odd sized or
Shaped ADP’s
Disorder?
Fourier
difference
map
Check atomic
assignments
Switch unusual atom(s) to isotropic refinement
Wrong atom
type(s)?

25. * Workshops on these will be given later
Refinement
Common problems
Wrongly assigned atoms
Disorder, particularly solvent*
Twinning*
Incorrect space group
Q-Peaks due to strong absorption (heavy metals present)
Not all refinements will end happily
You may have to leave some atoms isotropic
You may be unable to find or place hydrogen atoms
You may have a high R-factor
You may simply not be able to finish due to the above issues or poor quality data
* Workshops on these will be given later

26. Shelx Anatomy of a shelx file TITL SAMPLE in Pbca
CELL
ZERR
LATT 1
SYMM 0.5-X, -Y, 0.5+Z
SYMM -X, 0.5+Y, 0.5-Z
SYMM 0.5+X, 0.5-Y, -Z
SFAC C H N O
UNIT
TEMP -123
L.S. 4
BOND $H
FMAP 2
ACTA
CONF
PLAN 20
WGHT
FVAR
O =
C = O C
HKLF 4
REM HL9005 in Pbca
REM R1 = for Fo > 4sig(Fo) and for all data
REM parameters refined using restraints
END
WGHT
REM Highest difference peak , deepest hole , 1-sigma level Q Q Q Q Q Q
Anatomy of a shelx file

27. Common Shelx Commands L.S.
Full least squares refinement. Number of cycles given after a space, e.g. L.S. 4 will give 4 refinement cycles
CGLS
Conjugate gradient least squares. Use for faster refinement with very large structures but only during initial refinement. You must switch to L.S. before generating a cif.
FMAP
Followed by a number requests a Fourier map. Normally you will use FMAP 2, for a difference map
PLAN
The number of peaks to be returned from the difference map, e.g. PLAN 20 gives 20 peaks.
BOND
Put Bonds into the cif file, always use BOND $H
ACTA
A cif will be generated
WGHT
This is the weighting scheme which will be used
FVAR
Free variables, the first is the overall scale factor. Others may be used for various purposes
SADI
Same distance restraint, e.g. SADI C1 C2 C3 C4 instructs the program to restrain the C1…C2 distance to be similar to the C3…C4 distance
SAME
Generates similarity restraints for extended geometries
DFIX
Distance restraint e.g. DFIX 1.54 C1 C2 puts a restraint on the C1…C2 distance to be 1.54 angstroms
SIMU
Similar thermal parameters will be applied to all atoms in the list following
DELU
Vibration restraint. The two atoms will be restrained to have similar motion along the direction of the bond
AFIX
Constraints. Many types available
HFIX
Add hydrogen atoms, many options available for different hydrogen environments

28. Back to our example…

29. Restraints and constraints
A restraint allows a parameter to refine within limits
E.g. like applying a spring
A constraint fixes a parameter. It is not allowed to refine.
E.g. like applying rope
Restraints are treated as additional observations
Restraints have an associated e.s.d. i.e. a measure of how strict the restraint should be
Most commands have reasonable defaults
Use to correct poor geometry with chemical knowledge
Can use temporarily to maintain reasonable geometry when identifying a problem, e.g. disorder
Only use when necessary ensure e.g. distance restraints use an appropriate value, e.g. taken from CSD data
Make sure there isn’t an underlying problem before resorting to R&C
More on these in disorder workshop.

30. Atomic assignment problems
Models are a picture of electron density
Different elements have different numbers of electrons
Incorrect assignments should show up in thermal parameters.
Too small an element will cause the ADP to shrink
Too large an element will cause it to grow
Why?

31. Atomic assignment problems
Atom is actually a nitrogen which has higher z and therefore e- density than our modelled carbon. Therefore the carbon ‘shrinks’ to increase its e- density
Atom is actually a carbon which has lower e- density than our model. Therefore the
nitrogen ‘grows’ to spread out its e- density

32. Hydrogen atoms Difficult to find Incorrectly located
Only one electron to diffract from
Heavier elements further obscure hydrogen positions
Incorrectly located
Diffract from electrons not nuclei!!!
Valence electron only, located ‘in bond’

33. Hydrogen placement Find them if you can Geometric placement
They may often be visible in a difference map
You may then be able to refine, partially refine them or constrain them.
Geometric placement
Uses expected (e.g. tetrahedral) angles and distances appropriate for x-ray diffraction
HFIX mn
m specifies how to place e.g. tetrahedral angles
n specifies how to refine, e.g. full coords or riding

34. Hydrogen Placement
Common HFIX types 1 2 3 4 8

35. Some Quality indicators
The conventional R-factor
<10% is publishable
<5% is good
Goof
Goodness of fit
Should be as close to 1 as possible
More than around 0.4 away is cause for concern
Rint
An R-factor for data merging of equivalent reflections
If perfect would be 0
A rough guide is to expect R1 to be close to this value
Max Shift
The max shift of all parameters from non-linear least squares refinement
Should be zero for a properly converged, finished model.

36. Finishing off Confident the structure is ok? Platon checkcif
IUCr web tool
Platon
Does additional checks if FCF file is present
Make sure it is up to date!