1. Freezing of Molecular Motions Probed by Cryogenic Magic Angle Spinning NMR Speaker : Marison (603260083) Date : 2016/05/02 Department of Chemistry and Biochemistry Maria ConcistrèMaria Concistrè, Elisa Carignani, Silvia Borsacchi, Ole G. Johannessen, Benedetta Mennucci, Yifeng Yang, Marco Geppi, and Malcolm H. Levitt*Elisa CarignaniSilvia BorsacchiOle G. JohannessenBenedetta MennucciYifeng YangMarco GeppiMalcolm H. Levitt* School of Chemistry, University of Southampton, SO17 1BJ Southampton, United Kingdom Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, 56126 Pisa, Italy School of Engineering Science, University of Southampton, Southampton, United Kingdom J. Phys. Chem. Lett., 2014, 5 (3), pp 512–516 DOI: 10.1021/jz4026276

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3. Research funding 2014-2018, "Molecular Endofullerenes: Nanoscale dipoles, rotors and oscillators", EPSRC, £1.03M 2012-2013 "Fast Sample Shuttle Probe for Nuclear Magnetic Resonance", Royal Society, £72k 2012-2016 "Hyperpolarized Singlet NMR", ERC Advanced Grant, £2.4M 2012-2014 "Laboratory for Enhanced Magnetic Resonance Imaging", Royal Society, £393k 2011-2014 "Hyperpolarized Nuclear Singlet States", EPSRC, £1.4M (with Prof R. Brown, University of Southampton) 2011-2017 "A UK Magnetic Resonance Basic Technology Centre for Doctoral Training", £3.96M (with Universities of Warwick, St Andrews, Dundee, Nottingham and Aberdeen) 2011-2014 "Magnetic Resonance of Dihydrogen Endofullerenes", EPSRC, £606k (with Prof. A. J. Horsewill, University of Nottingham) 2009-2013 "Singlet nuclear magnetic resonance: from theory to practice", Leverhulme Trust, £249k 2007-2009 "Long-lived spin states in nuclear magnetic resonance", EPSRC, £348k. 2007-2010 "Multiple-spin recoupling in nuclear magnetic resonance", EPSRC, £450k. 2005-2009 "Cryogenic magic-angle-spinning NMR", Basic Technology Program, RCUK, £2.81M. Collaborative grant with Prof. P. J. F. Henderson, Department of Biochemistry, University of Leeds; Dr. A. Horsewill, School of Physics and Astronomy, University of Nottingham; Dr. M. Grossel, School of Chemistry, University of Southampton; Prof. Y. Yang, School of Engineering, University of Southampton; Dr. J. Werner, School of Biological Sciences, University of Southampton. 2005-2008 "Multiple-quantum 17O NMR in solids", Royal Society, £15.5k. Collaborative grant with Dr. P. K. Madhu, Tata Institute for Fundamental Research, Mumbai, India. Research funding 2014-2018, "Molecular Endofullerenes: Nanoscale dipoles, rotors and oscillators", EPSRC, £1.03M 2012-2013 "Fast Sample Shuttle Probe for Nuclear Magnetic Resonance", Royal Society, £72k 2012-2016 "Hyperpolarized Singlet NMR", ERC Advanced Grant, £2.4M 2012-2014 "Laboratory for Enhanced Magnetic Resonance Imaging", Royal Society, £393k 2011-2014 "Hyperpolarized Nuclear Singlet States", EPSRC, £1.4M (with Prof R. Brown, University of Southampton) 2011-2017 "A UK Magnetic Resonance Basic Technology Centre for Doctoral Training", £3.96M (with Universities of Warwick, St Andrews, Dundee, Nottingham and Aberdeen) 2011-2014 "Magnetic Resonance of Dihydrogen Endofullerenes", EPSRC, £606k (with Prof. A. J. Horsewill, University of Nottingham) 2009-2013 "Singlet nuclear magnetic resonance: from theory to practice", Leverhulme Trust, £249k 2007-2009 "Long-lived spin states in nuclear magnetic resonance", EPSRC, £348k. 2007-2010 "Multiple-spin recoupling in nuclear magnetic resonance", EPSRC, £450k. 2005-2009 "Cryogenic magic-angle-spinning NMR", Basic Technology Program, RCUK, £2.81M. Collaborative grant with Prof. P. J. F. Henderson, Department of Biochemistry, University of Leeds; Dr. A. Horsewill, School of Physics and Astronomy, University of Nottingham; Dr. M. Grossel, School of Chemistry, University of Southampton; Prof. Y. Yang, School of Engineering, University of Southampton; Dr. J. Werner, School of Biological Sciences, University of Southampton. 2005-2008 "Multiple-quantum 17O NMR in solids", Royal Society, £15.5k. Collaborative grant with Dr. P. K. Madhu, Tata Institute for Fundamental Research, Mumbai, India. Prof Malcolm Levitt joined the School of Chemistry at the University of Southampton in 2000, as Professor in Physical Chemistry. His main research area is Nuclear Magnetic Resonance (NMR), in which he has won several international prizes and has written a well- received textbook. “Nuclear magnetic resonance (NMR) is well known in the form of Magnetic Resonance Imaging (MRI), where it is used routinely for medical scanning. But NMR is a much wider field than MRI, and is still under intensive development. I particularly like NMR as a research field since it combines deep principles of quantum mechanics with numerous real-world applications, including chemistry, biochemistry, physics, and medicine.” Professor Malcolm H Levitt (Professor of Physical Chemistry )

4. Introduction Why this research is important What they know and don’t know Their experiment Their hypothesis Cryogenic magic angle spinning makes it possible to obtain the NMR spectra of solid at temperature low enough to freeze out most molecular motions. A They know that NMR signals are stronger at low temperatures due to Curie law nuclear paramagnetism, the radio frequency noise in the receiver coil is reduced at the same time. The study of cryogenic solid state phenomena such as superconductivity and quantum molecular rotation become possible, and in the context of biomolecular NMR, low temperature operation makes it possible to trap and study intermediate and functional state of proteins. Further more, the combination of MAS NMR with dynamics nuclear polarization (DNP) provides large NMR signal enhancements at low sample temperatures, which is particularly important for biomolecular structural studies. However, they don’t know yet at a very low sample temperature lead to broadening, or narrowing, of the solid state NMR spectra. Cryogenic MAS-NMR experiment, with particular attention on the dependence of 13 C LWs on temperature. The NMR spectrum is expected to display considerable inhomogeneous broadening in the cryogenic regime because a large number of inequivalent conformations are ‘’frozen in’’, each displaying different chemical shifts. Study of the dynamical processes occurring in IBU-S in the cryogenic regime.

5. DESIGN/METHOD Sample characterization Design and Method Solid state NMR experiments Analysis and calculation Exposure to atmospheric humidity for at least 4 ours. The crystal structure of the sample was checked by XRPD. Selection of 13 C C-CP-MAS spectra of IBU-S acquired in the temperature range from 358 to 20K. There were 4 series of sample recorded on different apparatus, including the magnetic field B 0, rotor diameter d r, and magic angle spinning frequency v r are as follows series I : B 0 = 9.4 T, d r = 7.5 mm, v r ≈ 5.0 kHz; series II : B 0 = 9.4 T, d r = 7.5 mm, v r ≈ 6.0 kHz; series III : B 0 = 9.4 T, d r = 4.0 mm, v r ≈ 5.0 kHz, series IV : B 0 = 14.1 T, d r = 2.0 mm, v r ≈ 9.0 kHz, Sample masses are 240 (I,II), 150 (III), and 1.5 mg(IV). DFT chemical shift calculations for the 13 C sites c, h, l, m, and n B3LYP functional and 6-311+G(d,p) basis set were used in GAUSSIAN09 for all NMR calculations.

6. NMR

7. Solid state Vs liquid state Non-destructive / “precious” samples Destructive sample Solid/semi-solid sample / Insoluble / No solvent needed Solvent needed

8. What is anisotropy ? How does it effect NMR spectra?

10. 54.73 0

11. MAS OFF MAS ON

13. Result

14. Chemical structure of the Ibuprofen (Na + C 13 H 17 O 2 - 2H 2 O) hydrophobic hydrophilic

18. Isotropic chemical shift distributions

19. Conclusion The hydrophobic and hydrophilic regions of IBU-S display constracting behavior in the context of cryogenic MAS NMR. The hydrophilic region remains well-structured at cryogenic temperatures and consistently display narrow peaks, except associated, methyl group, whose peak broadens due to hindered three-fold rotation at round 100 K but that narrow again at lower temperatures. The hydrophobic region, with its flexible isobutyl group, on the other hand, displays the NMR signature of a broad frozen conformational distribution at very low temperature. This study shows the range of phenomena that may be displayed, even by small molecules, in cryogenic solid state NMR.

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