Phase Diagram (p,T) Exploration by Neutron Powder Diffraction for Polymorph Discovery

1. Phase Diagram (p,T) Exploration by Neutron Powder Diffraction for Polymorph Discovery Charlie Broder ISIS, Rutherford Appleton Laboratory

2. Neutron Diffraction Computational Chemistry Structure Prediction Thermodynamics Raman / IR spectroscopy NMR DSC/TGA Polymorphism Robotic Screen Quantitative analysis Single Crystal X-ray diffraction Powder diffraction X-ray diffraction Nucleation / crystallisation studies Electron crystallography

3. Neutron Diffraction Single temperature SXD GEM Various Experiments Multi temperature PEARL Single crystal Temperature / Pressure OSIRIS Powder HRPD Multi Pressure Etc, etc Single Pressure Instruments at other neutron facilities

4. Phase Diagram (p,T) Exploration by Neutron Powder Diffraction for Polymorph Discovery Single temperature SXD GEM Various Experiments Multi temperature PEARL Single crystal Temperature / Pressure HRPD Powder OSIRIS Cyclopentane Multi Pressure Etc, etc Single Pressure Instruments at other neutron facilities

5. H C N O S Br Why neutron diffraction? Why Neutrons? Neutrons and X-rays interact with matter in different ways: X-rays interact with electrons Neutrons interact with the nucleus Scattering cross-sections X N

6. Why neutron diffraction? Why Neutrons? Neutrons and X-rays interact with matter in different ways: X-rays interact with electrons Neutrons interact with the nucleus Neutrons see hydrogen atoms and so hydrogen positions can be found very accurately … even with powders: Hydrogen bond lengths and angles can be accurately measured Accurate hydrogen positions for calculations AND… Hirschfeld surfaces

7. Why neutron diffraction?

8. Why neutron diffraction? H H H H H H

9. Why neutron diffraction? For crystal structure prediction … (Gavezzotti, Price) crystal structure prediction requires accurate intermolecular potentials requires accurate hydrogen positions requires neutrons!

10. Why neutron diffraction? Why Neutrons? Neutrons and X-rays interact with matter in different ways: X-rays interact with electrons Neutrons interact with the nucleus • Hydrogen atoms positions can be found accurately • Differences in scattering lengths means different pressure cell design to that for X-ray diffraction systems • Ease of control of sample environment •  X-ray and Neutron diffraction are complementary

11. Why neutron diffraction? Why neutron powder diffraction? • Quicker than single crystal diffraction so can collect data at lots of temperatures and/or pressures => identify new phases • Powders are easier to produce than single crystals • Less likely to get sample deterioration on phase change Single crystal → not single crystal Powder → finer powder

12. So what is the down side… • there are not many neutron sources around the world • but … really good ideas always get beam-time! • loss of data: powder data set contain less information than a single crystal data set • difference in the way neutrons and X-rays interact with matter means that standard structure solution methods do not usually work.

13. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) constant λ source (monochromatic) → scan though θ with a white beam scan though λ → keep θ constant How do you scan though the λ of a white beam? → use time-of-flight methods

14. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector Flight path

15. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

16. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

17. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

18. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

19. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

20. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

21. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

22. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

23. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

24. ISIS & time of flight • World’s brightest pulsed neutron and muon source. Diffraction is dependent on wavelength λ = 2d sinθ(Braggs Law) Pulse Detector

25. ISIS & HRPD

26. HRPD HRPD

27. High Resolution Powder Diffactometer HRPD Neutron flight path Travel down flight path Resolution at HRPD Resolution in experimental hall

28. Detector backscattering Detector backscattering Sample environment Detector low angle Sample Detector 90° (South) Detector 90° (North) Neutron beam

29. Cyclopentane • Simple molecule • Structure has never been solved by diffraction methods • Study [1] claims 3 phases at atmospheric pressure + 4th high pressure phase • Phase I and phase II have been show to be highly disordered plastic crystals. • Phase I has been indexed to a hexagonal unit cell (5.830Å 5.830Å 9.330Å 90º 90º 120º at 295K) [2] but the structure has not been solved. • Phases II and III have not been indexed. • Phase III has been solved by Roland Boese (unpublished result) 1) D.S.Webster, M.J.R.Hoch, J. Phys. Chem. Solids 1976,37, 351 2) B.Post, R.S.Schwartz, I.Frankuchen, J. Phys. Chem. Solids 1951, 73, 5113

30. Cyclopentane • Blue = phase I • Green = phase II • Red = phase III 201 pT data points, ~7 μAh for atmospheric pressure runs ~17μAh at higher pressures

31. Cyclopentane –the data Backscattering data bank 0.6-2.7Å d-spacing 90 degree data bank 0.9-3.7Å d-spacing Low angle (30°) data bank 2.3-9.9Å d-spacing Good quality data Poor quality data Disordered / Plastic Poor quality data Disordered / Plastic

32. 182K 180K 178K 176K 174K 172K 170K Cyclopentane Phase IV: Does not exist! We did not obtain Phase IV in this experiment • Blue = phase I • Green = phase II • Red = phase III • Black line = published phase diagram (Webster and Hock 1976) 201 pT data points, ~7 μAh for atmospheric pressure runs ~17μAh at higher pressures

33. Cyclopentane Phase 1 Indexed to Hexagonal 5.69 5.69 9.23 90 90 120 at 140K Data might be good enough for structural refinement 144K 142K 140K 138K 136K 134K 132K 130K

34. Cyclopentane Phase II • Poor data, weak peaks, high background • highly disordered • Almost certainly unsolvable data Data is only good enough to index

35. Cyclopentane Phase III • Indexed to Monoclinic • 10.035.35 9.61 90 113.2 90 at 100K • Data give good fit for a Pawley refinement • Pawley refinement of backscattering data bank: • Rwp = 13.357 • Cell refined to: • 9.96562 5.29629 9.54602 90.0 113.66515 90.0 • Space group = P21 • What next: • Solve Data • Carry out Pawley refinements to refine • lattice parameters at each temperature • → to track structural changes as a • function of pressure and temperature. 130K 128K 126K 124K 122K 120K 118K 116K

36. Cyclopentane Phase 3 – Pawley fit

37. Conclusions Phase Diagram (p,T) Exploration by Neutron Powder Diffraction for Polymorph Discovery: • Neutron powder diffraction can be used to study polymorphic phase transitions in situ. • Neutron diffraction is a very powerful technique for exploring the pT phase diagram. • Powder diffraction is the best way to obtain useable data across a fine enough grid to fully explore the pT phase diagram.

38. Acknowledgments Bill David, Kenneth Shankland, Chick Wilson Sally Price and my colleagues on the CPOSS project Richard Ibberson (HRPD Instrument scientist ISIS) And For Funding: U.K. Research Councils Basic Technologies Program CCLRC And Mark Spackman and Sally Price for letting me use their slides in this presentation!!