A quick guide to crystallography and crystal growth

Ross Harrington

Outline

What is crystallography?

How it works and why you need good crystals

The data collection procedureWhere the pitfalls lie.

What are crystals? Crystal growth Factors that affect diffraction quality National Service and Diamond

Books

What is crystallography?

Determining the 3-D structure of a molecule

Provides relationship of structure to physical and chemical properties

Meaning of ‘structure’: relative positions of atoms in a molecular or other

material, hence complete geometrical description: bond lengths and angles molecular conformation absolute configuration, etc.

Absolute Configuration

The ‘absolute structure’ defines the configuration of the chiral centres in a molecule that is chirally pure (i.e. R or S).

In this case molecules will crystallise in a chiral space group i.e. One with no centre of symmetry (mirror or inversion centre)

Can not apply to racemic mixtures or molecules that contain internal symmetry

What is crystallography?

Not a spectroscopic technique

All parts of the diffraction pattern contribute to all parts of the structure

So- all parts of the structure also contribute to all parts of the diffraction pattern.

The two techniques

Spectroscopy

UV, light, IR, etc.

Crystallography

X-rays (or neutrons)Usually monochrmoatic

Sample

detector: measure the variation of intensity with changing λ in one direction

Crystal

detector: measure the variation of intensity with direction for one λ (a diffraction pattern)

Diffraction

X-rays interact with the electrons surrounding the nuclei (and in the bonds)

So the heavier the atom, the more electrons are present, so diffraction is more intense.

Diffraction is proportional to the number of electrons present

Diffraction drops off at higher angle of incidence (theta)

So locating H atoms is difficult

Other points of note

Each spot in a diffraction pattern is one data point (h,k,l).

The number of data points possible is proportional to the size of the unit cell

The size of the unit cell is proportional to the size of the molecule being analysed.

So bigger molecules take longer to obtain data.

What is a crystal?

A solid material with infinite order in three dimensions

Therefore all molecules are in exactly the same relative environment

This means that translational and possibly other symmetry is present

These are:

Inversion centres, rotation axes and mirrors

Defining a unit cell

The Process

The Experiment

Grow Crystals

Select Crystal

Collect/process data

Solve and refine structure

Publish/Patent

Grow good crystals

Garbage in = Garbage out

Relatively large See-through/clear Single Not amorphous

1. Grow good crystals

General principles of crystal growth

It isn’t the same as recrystallisation Crystals grow in a settled environment Solvents make a big difference- both purity

and volatility Solubility is important Seeding can work The first try isn’t always the best Take Time....

Choose your vessel carefully

Crystals need to be removed easily Don’t use huge vessels with small volumes Try to avoid vessels with very small

apertures Try to avoid vessels with wide shoulders Avoid very smooth or very scratched

vessels

My least favourite

Crystal Growth: Solution methods

General principles

Choose your solvents carefully- ‘like dissolves like’

Anti-solvents can be added to reduce solubility

Varying concentrations of the two can give the best conditions for crystallisation

Crystal Growth: Concentration

Essentially ‘slow evaporation’ If using mixed solvents, the better solvent

should be most volatile. Rate of evaporation can be controlled:

Temperature Gas flow Aperture size

Note: Avoid hazards such as build up solvent in confined spaces.

Keep an eye on the sample.

Examples

NMR tubes left in back of Fume Cupboard

Crystal Growth: Slow cooling

Two methods: Allow a hot, almost saturated solution to cool

slowly to room temperature Cool a similar solution made up at RT, using

a fridge or freezer

Cooling time can be manipulated

Examples

Crystal Growth:Solvent diffusion

Essentially two almost immiscible solvents layered on top of each other

The poorer solvent mixes with the better solvent and causes crystallisation

Can also use specialist apparatus such as H-cells

Examples

Crystal Growth: Vapour Diffusion

Relies on solvent/antisolvent principle again One sample tube inside another Volatile anti-solvent diffuses into solution via

the vapour phase This reduces solubility and hence

crystallisation occurs.

Examples

Crystal Growth: Exotic methods

Sublimation Convection In situ crystallisation Reactant diffusion Solid synthesis (grinding) Solvothermal (temp and pressure)

When you get crystals

DO NOT filter them DO NOT put them under vacuum DO NOT let them dry out DO leave them in the same environment DO reduce the solvent level slightly DO give us as many crystals as possible

Re-growing crystals

Tend not to say ‘recrystallise’ SD example CH2Cl2 vs CHCl3

Re-growing crystals

R1 = 0.0210, wR2 = 0.0544Largest peak and hole 0.87 and 0.54 e Å3

Collecting the data

Choosing the crystal (up to 15 minutes) Collecting initial images (10 minutes) Checking against known cell (5 minutes) Data collection (30 minutes to 3 days) Processing data (20 minutes) Solving and refining structure (30 minutes to

a week) Publishing structure (up to 15 years)

What I am aiming for

Good enough to get a structure? Resolution limits (0.84Å Mo, 0.9Å Cu)? Publishable in Acta?

‘The best possible data you can get from the sample you have’

‘Data out’

As high a resolution as possible

High redundancy on all reflections (at least 2)

Good statistics (Rsigma, Rint) on whole data set

Low residual peaks in the difference map

A good R factor

Good and bad patterns

Good and bad patterns

Effect of disorder ?

R1 = 0.0437, wR2 = 0.0938Largest diff. peak and hole 0.43 and 0.27 e Å3

Effect of disorder ?

R1 = 0.0562, wR2 = 0.1196Largest diff. peak and hole 0.96 and 0.40 e Å3

Twinning

Twinning occurs where the unit cell has symmetry elements that the contents of the cell do not

Example: A Monoclinic structure with β close to 90o

Two types of Twinning Merohedral: occurs where lattice system has

two point groups Non-merohedral: imperfect overlap of

diffraction from two components

Consequences of twinning

Consequences of twinning

Pros and cons of crystallography

Pros Relatively quick Unambiguous Loads of info Picture tells a thousand

words

Cons You have to grow crystals Selected crystal may not

be representative Solid state may be

different from solution Not useful for elemental

analysis

You will need supporting evidence for analysis of the bulk sample e.g. Powder diffraction

When all else fails...

Use a stronger X-ray source We have access to:

The National Service (rotating anodes and mirrors) ~15 samples in 6 months

Diamond Light Source (synchrotron)

~ 4 days every 6 months