1. A quick guide to crystallography and crystal growth Ross Harrington

2. Outline  What is crystallography? How it works and why you need good crystals  The data collection procedure Where the pitfalls lie.  What are crystals?  Crystal growth  Factors that affect diffraction quality  National Service and Diamond

3. Books

4. 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.

5. 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

6. 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.

7. 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)

8. 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

9. 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.

10. 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

11. Defining a unit cell

12. The Process

13. The Experiment Grow Crystals Select Crystal Collect/process data Solve and refine structure Publish/Patent

14. Grow good crystals Garbage in = Garbage out  Relatively large  See-through/clear  Single  Not amorphous

15. 1. Grow good crystals

25. 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....

26. 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

27. My least favourite

28. 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

29. 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.

30. Examples  NMR tubes left in back of Fume Cupboard

32. 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

33. Examples

34. 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

35. Examples

36. 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.

37. Examples

38. Crystal Growth: Exotic methods  Sublimation  Convection  In situ crystallisation  Reactant diffusion  Solid synthesis (grinding)  Solvothermal (temp and pressure)

40. 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

41. Re-growing crystals  Tend not to say ‘recrystallise’  SD example CH 2 Cl 2 vs CHCl 3

42. Re-growing crystals R1 = 0.0210, wR2 = 0.0544 Largest peak and hole 0.87 and  0.54 e Å  3

43. 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)

44. 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’

45. ‘Data out’  As high a resolution as possible  High redundancy on all reflections (at least 2)  Good statistics (R sigma, R int ) on whole data set  Low residual peaks in the difference map  A good R factor

46. Good and bad patterns

48. Effect of disorder ? R1 = 0.0437, wR2 = 0.0938 Largest diff. peak and hole0.43 and  0.27 e Å  3

49. Effect of disorder ? R1 = 0.0562, wR2 = 0.1196 Largest diff. peak and hole 0.96 and  0.40 e Å  3

50. 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 90 o  Two types of Twinning  Merohedral: occurs where lattice system has two point groups  Non-merohedral: imperfect overlap of diffraction from two components

51. Consequences of twinning

53. 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

54. 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