• Shelx
– http://shelx.uni-ac.gwdg.de/SHELX/
• WinGX
– http://www.chem.gla.ac.uk/~louis/software/wingx/
• Platon
– http://www.chem.gla.ac.uk/~louis/software/platon/
• Solution programs (see later)
• A good text editor
– e.g. Notepad++
• http://notepad-plus.sourceforge.net/uk/site.htm

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

• 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

– 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)

TITL pg24 in P-1
CELL 0.71073 10.724 12.440 12.643 72.40 79.36 73.33
ZERR 2.00 0.004 0.005 0.005 0.02 0.02 0.02
LATT 1
SFAC C H N S HG
UNIT 52 106 2 6 2
PATT
HKLF 4
END

-12 0 1 64.46 2.70
-12 -1 2 47.71 3.70
-12 -1 1 41.90 3.48
-12 -2 1 15.71 0.80
-12 -2 2 41.02 1.56
-12 -3 2 20.34 0.97
-12 -3 1 2.96 0.62
-12 -4 1 27.33 1.27
-12 -4 2 21.33 1.05
-12 -5 1 60.67 2.48
-12 -6 1 66.61 2.61
-11 -8 2 9.18 0.73
-11 -8 1 37.45 1.50
-11 -7 1 3.94 0.59
-11 -7 2 92.96 4.46
-11 -7 3 46.55 2.36
-11 -6 3 16.54 0.86
-11 -6 2 135.97 3.44
-11 -6 1 9.06 0.72

– 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.

• Direct methods
– Requirements
• 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.

• 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.

• Patterson Methods
– Requirements
• 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

– 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.

• 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.

– 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

• Charge flipping
– Requirements
• 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

– Superflip
• From originators of the method
• Available as standalone (not recommended), via
WinGX, via crystals
– Flipper
• Available in Platon

• 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

• 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.

– Crystal structure determination
• William Clegg

• 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

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

• 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

TITL SAMPLE in Pbca
CELL 0.71073 10.7308 16.4002 18.9778 90.000 90.000 90.000
ZERR 8.00 0.0005 0.0007 0.0008 0.000 0.000 0.000
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 160 152 8 32
TEMP -123
L.S. 4
BOND $H
FMAP 2
ACTA
CONF
PLAN 20
WGHT 0.040400 1.691300
FVAR 0.13360
O1 4 1.183095 0.526967 0.621173 11.00000 0.04325 0.03499 =
0.02675 -0.00293 -0.00093 -0.01115
C2 1 1.183370 0.488078 0.567136 11.00000 0.02854 0.02571 =
0.02494 0.00436 -0.00205 -0.00215
O3 4 1.266176 0.500831 0.515249 11.00000 0.03273
C4 1 1.239322 0.447764 0.456425 11.00000 0.03222
HKLF 4
REM HL9005 in Pbca
REM R1 = 0.0452 for 3267 Fo > 4sig(Fo) and 0.0476 for all 3421 data
REM 226 parameters refined using 0 restraints
END
WGHT 0.0404 1.6913
REM Highest difference peak 0.267, deepest hole -0.198, 1-sigma level 0.039
Q1 1 0.8842 0.3387 0.6174 11.00000 0.05 0.27
Q2 1 0.9964 0.3517 0.6038 11.00000 0.05 0.24
Q3 1 0.9221 0.3187 0.5592 11.00000 0.05 0.23
Q4 1 0.6446 0.2208 0.7061 11.00000 0.05 0.22
Q5 1 0.9203 0.3060 0.4928 11.00000 0.05 0.21
Q6 1 0.9370 0.3938 0.5769 11.00000 0.05 0.20

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
DFIX
Generates similarity restraints for extended geometries
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

• 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.

– 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?

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

– Only one electron to diffract from
– Heavier elements further obscure hydrogen positions
– Diffract from electrons not nuclei!!!
– Valence electron only, located ‘in bond’

– They may often be visible in a difference map
– You may then be able to refine, partially refine them or constrain them.
– 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

• Common HFIX types
1 2 3
4 8

• R
1
– 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
• R int
– An R-factor for data merging of equivalent reflections
– If perfect would be 0
– A rough guide is to expect R
1
• Max Shift to be close to this value
– The max shift of all parameters from non-linear least squares refinement
– Should be zero for a properly converged, finished model.

– IUCr web tool
• http://checkcif.iucr.org/
– Platon
• Does additional checks if FCF file is present
• Make sure it is up to date!