Advertisement

High-Resolution Proton NMR Spectroscopy of Polymers and Biological Solids

Reference work entry

Abstract

Proton NMR spectroscopy of solids has traditionally been challenging due to the widespread presence of strong 1H-1H dipolar couplings in solid systems, which severely broaden proton NMR spectral lines and result in the loss of chemical resolution. Nonetheless, recent developments in magic-angle-spinning (MAS) NMR probe technology and solid-state NMR methodology have provided excellent opportunities for significant improvements in the resolution of 1H NMR spectra of solids. As a result, proton NMR spectroscopy has emerged as a valuable tool for obtaining atomic-level insights into the molecular structures and dynamics in various challenging systems. In this chapter, proton-based solid-state NMR strategies for achieving high spectral resolution will be reviewed in conjunction with their applications to various challenging systems. Three different solid-state NMR approaches to enhance the proton spectral resolution are covered in this chapter: combined rotation and multiple pulse spectroscopy (CRAMPS), high-resolution MAS spectroscopy (HRMAS), and ultrafast MAS (UFMAS). CRAMPS technique is often used for enhancing spectral resolution at slow spinning rates, whereas HRMAS has been used in the study of semisolids such as membrane mimetics including bicelles and nanodiscs, liquid crystalline materials, tissues, and biospecimens. Thanks to the recent NMR hardware and methodology advances, UFMAS experiments are increasingly applied to obtain ultrahigh resolution proton spectra of various challenging materials. Due to the high gyromagnetic ratio, high natural-abundance and prevalence of protons in various systems, it is expected that proton NMR spectroscopy will play more significant roles in the investigation of molecular structures and dynamics.

Keywords

Solid-State NMR 1H NMR High resolution CRAMPS HRMAS Ultrafast MAS NOESY RFDR Chemical shift anisotropy Proton detection 

Notes

Acknowledgments

We acknowledge the financial support from the National Institutes of Health (to A.R.). We would like to thank Dr. Yusuke Nishiyama and JEOL RESONANCE for fruitful collaborations in the development of ultrafast-MAS techniques using a 0.75 mm 120 kHz MAS probe.

References

  1. 1.
    Schmidt-Rohr K, Spiess HW. Multidimensional solid-state NMR and polymers. London: Academic; 1994.Google Scholar
  2. 2.
    Duer MJ. Solid state NMR spectroscopy: principles and applications. Oxford: Wiley-Blackwell; 2001.CrossRefGoogle Scholar
  3. 3.
    Ramamoorthy A. NMR spectroscopy of biological solids. Boca Raton: CRC Press; 2010.Google Scholar
  4. 4.
    McDermott AE, Polenova T. Solid state NMR studies of biopolymers. Chichester: Wiley; 2012.Google Scholar
  5. 5.
    Cross TA, Opella SJ. Solid-state NMR structural studies of peptides and proteins in membranes. Curr Opin Struct Biol. 1994;4(4):574–81.CrossRefGoogle Scholar
  6. 6.
    Ernst RR, Bodenhausen G, Wokaun A. Principles of nuclear magnetic resonance in one and two dimensions. Oxford: Clarendon Press; 1987.Google Scholar
  7. 7.
    Levitt MH. Symmetry-based pulse sequences in magic-angle spinning solid-state NMR. eMagRes. Chichester: Wiley; 2007.Google Scholar
  8. 8.
    Fujiwara T, Ramamoorthy A. How far can the sensitivity of NMR be increased? Annu Rep NMR Spectrosc. 2006;58:155–75.CrossRefGoogle Scholar
  9. 9.
    Su Y, Andreas L, Griffin RG. Magic angle spinning NMR of proteins: high-frequency dynamic nuclear polarization and 1H detection. Annu Rev Biochem. 2015;84:465–97.CrossRefGoogle Scholar
  10. 10.
    Hong M, Schmidt-Rohr K. Magic-angle-spinning NMR techniques for measuring long-range distances in biological macromolecules. Acc Chem Res. 2013;46(9):2154–63.CrossRefGoogle Scholar
  11. 11.
    Saitô H, Ando I, Ramamoorthy A. Chemical shift tensor – the heart of NMR: insights into biological aspects of proteins. Prog Nucl Magn Reson Spectrosc. 2010;57(2):181–228.CrossRefGoogle Scholar
  12. 12.
    Haeberlen U. High resolution NMR in solids selective averaging. Academic Press, New York, 1976.CrossRefGoogle Scholar
  13. 13.
    Mehring M. Principles of high resolution NMR in solids, Springer-Verlag, New York, 1983.CrossRefGoogle Scholar
  14. 14.
    Bielecki A, Kolbert A, De Groot H, Griffin R, Levitt M. Frequency-switched Lee-Goldburg sequences in solids. Adv Magn Reson. 1990;14:111.CrossRefGoogle Scholar
  15. 15.
    Mote KR, Agarwal V, Madhu PK. Five decades of homonuclear dipolar decoupling in solid-state NMR: status and outlook. Prog Nucl Magn Reson Spectrosc. 2016;97:1–39.CrossRefGoogle Scholar
  16. 16.
    Chevelkov V, Rehbein K, Diehl A, Reif B. Ultrahigh resolution in proton solid-state NMR spectroscopy at high levels of deuteration. Angew Chem Int Ed. 2006;45(23):3878–81.CrossRefGoogle Scholar
  17. 17.
    Nishiyama Y. Fast magic-angle sample spinning solid-state NMR at 60–100 kHz for natural abundance samples. Solid State Nucl Magn Reson. 2016;78:24–36.CrossRefGoogle Scholar
  18. 18.
    Pandey MK, Zhang R, Hashi K, Ohki S, Nishijima G, Matsumoto S, et al. 1020 MHz single-channel proton fast magic angle spinning solid-state NMR spectroscopy. J Magn Reson. 2015;261:1–5.CrossRefGoogle Scholar
  19. 19.
    Agarwal V, Penzel S, Szekely K, Cadalbert R, Testori E, Oss A, et al. De novo 3D structure determination from sub-milligram protein samples by solid-state 100 kHz MAS NMR spectroscopy. Angew Chem Int Ed. 2014;53(45):12253–6.CrossRefGoogle Scholar
  20. 20.
    Asami S, Reif B. Proton-Detected Solid-State NMR Spectroscopy at Aliphatic Sites: Application to Crystalline Systems. Acc Chem Res. 2013;46(9):2089–97.CrossRefGoogle Scholar
  21. 21.
    Stanek J, Andreas LB, Jaudzems K, Cala D, Lalli D, Bertarello A, et al. NMR spectroscopic assignment of backbone and side-chain protons in fully protonated proteins: microcrystals, sedimented assemblies, and amyloid fibrils. Angew Chem Int Ed. 2016;55(50):15504–9.CrossRefGoogle Scholar
  22. 22.
    Fricke P, Chevelkov V, Zinke M, Giller K, Becker S, Lange A. Backbone assignment of perdeuterated proteins by solid-state NMR using proton detection and ultrafast magic-angle spinning. Nat Protoc. 2017;12(4):764–82.CrossRefGoogle Scholar
  23. 23.
    Barbet-Massin E, Pell AJ, Retel JS, Andreas LB, Jaudzems K, Franks WT, et al. Rapid proton-detected NMR assignment for proteins with fast magic angle spinning. J Am Chem Soc. 2014;136(35):12489–97.CrossRefGoogle Scholar
  24. 24.
    Ye YQ, Malon M, Martineau C, Taulelle F, Nishiyama Y. Rapid measurement of multidimensional 1H solid-state NMR spectra at ultra-fast MAS frequencies. J Magn Reson. 2014;239:75–80.CrossRefGoogle Scholar
  25. 25.
    Demers J-P, Vijayan V, Lange A. Recovery of bulk proton magnetization and sensitivity enhancement in ultra-fast magic-angle spinning solid-state NMR. J Phys Chem B. 2015;119(7):2908–20.CrossRefGoogle Scholar
  26. 26.
    Zhang R, Chen Y, Rodriguez-Hornedo N, Ramamoorthy A. Enhancing NMR sensitivity of natural-abundance low-γ nuclei by ultrafast magic-angle-spinning solid-state NMR spectroscopy. ChemPhysChem. 2016;17(19):2962–6.CrossRefGoogle Scholar
  27. 27.
    Johnson RL, Schmidt-Rohr K. Quantitative solid-state 13C NMR with signal enhancement by multiple cross polarization. J Magn Reson. 2014;239:44–9.CrossRefGoogle Scholar
  28. 28.
    Zhang R, Ramamoorthy A. Performance of RINEPT is amplified by dipolar couplings under ultrafast MAS conditions. J Magn Reson. 2014;243:85–92.CrossRefGoogle Scholar
  29. 29.
    Lee M, Goldburg WI. Nuclear-magnetic-resonance line narrowing by a rotating rf field. Phys Rev. 1965;140(4A):A1261–A71.CrossRefGoogle Scholar
  30. 30.
    Waugh J, Huber L, Haeberlen U. Approach to high-resolution NMR in solids. Phys Rev Lett. 1968;20(5):180.CrossRefGoogle Scholar
  31. 31.
    Schaefer J, Stejskal EO. Carbon-13 nuclear magnetic resonance of polymers spinning at the magic angle. J Am Chem Soc. 1976;98(4):1031–2.CrossRefGoogle Scholar
  32. 32.
    Bielecki A, Kolbert AC, Levitt MH. Frequency-switched pulse sequences: homonuclear decoupling and dilute spin NMR in solids. Chem Phys Lett. 1989;155(4–5):341–6.CrossRefGoogle Scholar
  33. 33.
    Mehring M, Waugh JS. Magic-angle NMR experiments in solids. Phys Rev B. 1972;5(9):3459–71.CrossRefGoogle Scholar
  34. 34.
    Vinogradov E, Madhu PK, Vega S. High-resolution proton solid-state NMR spectroscopy by phase-modulated Lee–Goldburg experiment. Chem Phys Lett. 1999;314(5–6):443–50.CrossRefGoogle Scholar
  35. 35.
    Sakellariou D, Lesage A, Hodgkinson P, Emsley L. Homonuclear dipolar decoupling in solid-state NMR using continuous phase modulation. Chem Phys Lett. 2000;319(3–4):253–60.CrossRefGoogle Scholar
  36. 36.
    Li B, Xu L, Wu Q, Chen T, Sun P, Jin Q, et al. Various types of hydrogen bonds, their temperature dependence and water-polymer interaction in hydrated poly(acrylic acid) as revealed by H-1 solid-state NMR spectroscopy. Macromolecules. 2007;40:5776–86.CrossRefGoogle Scholar
  37. 37.
    Brown SP. Probing proton-proton proximities in the solid state. Prog Nucl Magn Reson Spectrosc. 2007;50:199–251.CrossRefGoogle Scholar
  38. 38.
    He X, Liu Y, Zhang R, Wu Q, Chen T, Sun P, et al. Unique interphase and cross-linked network controlled by different miscible blocks in nanostructured epoxy/block copolymer blends characterized by solid-state NMR. J Phys Chem C. 2014;118(24):13285–99.CrossRefGoogle Scholar
  39. 39.
    Dang Q, Lu S, Yu S, Sun P, Yuan Z. Silk fibroin/montmorillonite nanocomposites: effect of ph on the conformational transition and clay dispersion. Biomacromolecules. 2010;11(7):1796–801.CrossRefGoogle Scholar
  40. 40.
    Wei Y, Lee D-K, Hallock KJ, Ramamoorthy A. One-dimensional 1H- detected solid-state NMR experiment to determine amide-1H chemical shifts in peptides. Chem Phys Lett. 2002;351(1–2):42–6.CrossRefGoogle Scholar
  41. 41.
    Fw W, Sun P. Solid state NMR study of hydrogen bonding, miscibility, and dynamics in multiphase polymer systems. Front Chem China. 2011;06(3):173–89.CrossRefGoogle Scholar
  42. 42.
    Wang F, Zhang R, Wu Q, Chen T, Sun P, Shi A-C. Probing the nanostructure, interfacial interaction and dynamics of chitosan-based nanoparticles by multiscale solid-state NMR. ACS Appl Mater Interfaces. 2014;6(23):21397–407.CrossRefGoogle Scholar
  43. 43.
    Brown SP. Applications of high-resolution 1H solid-state NMR. Solid State Nucl Magn Reson. 2012;41:1–27.CrossRefGoogle Scholar
  44. 44.
    Maas WE, Laukien FH, Cory DG. Gradient, high resolution, magic angle sample spinning NMR. J Am Chem Soc. 1996;118(51):13085–6.CrossRefGoogle Scholar
  45. 45.
    Wu C, Wang X. Globule-to-coil transition of a single homopolymer chain in solution. Phys Rev Lett. 1998;80(18):4092.CrossRefGoogle Scholar
  46. 46.
    Wang J, Liu B, Ru G, Bai J, Feng J. Effect of urea on phase transition of poly(N-isopropylacrylamide) and poly(N,N-diethylacrylamide) hydrogels: a clue for urea-induced denaturation. Macromolecules. 2016;49(1):234–43.CrossRefGoogle Scholar
  47. 47.
    Zhang R, Yan T, Lechner B-D, Schröter K, Liang Y, Li B, et al. Heterogeneity, segmental and hydrogen bond dynamics, and aging of supramolecular self-healing rubber. Macromolecules. 2013;46(5):1841–50.CrossRefGoogle Scholar
  48. 48.
    Pandey MK, Vivekanandan S, Yamamoto K, Im S, Waskell L, Ramamoorthy A. Proton-detected 2D radio frequency driven recoupling solid-state NMR studies on micelle-associated cytochrome-b5. J Magn Reson. 2014;242:169–79.CrossRefGoogle Scholar
  49. 49.
    Ramamoorthy A, Xu J. 2D 1H/1H RFDR and NOESY NMR experiments on a membrane-bound antimicrobial peptide under magic angle spinning. J Phys Chem B. 2013;117(22):6693–700.CrossRefGoogle Scholar
  50. 50.
    Bennett AE, Griffin RG, Ok JH, Vega S. Chemical shift correlation spectroscopy in rotating solids: radio frequency-driven dipolar recoupling and longitudinal exchange. J Chem Phys. 1992;96(11):8624–7.CrossRefGoogle Scholar
  51. 51.
    Mroue KH, Xu J, Zhu P, Morris MD, Ramamoorthy A. Selective detection and complete identification of triglycerides in cortical bone by high-resolution 1H MAS NMR spectroscopy. Phys Chem Chem Phys. 2016;18(28):18687–91.CrossRefGoogle Scholar
  52. 52.
    Chen L, Olsen RA, Elliott DW, Boettcher JM, Zhou DH, Rienstra CM, et al. Constant-time through-bond 13C correlation spectroscopy for assigning protein resonances with solid-state NMR spectroscopy. J Am Chem Soc. 2006;128(31):9992–3.CrossRefGoogle Scholar
  53. 53.
    Girvin ME. Increased sensitivity of COSY spectra by use of constant-time t1 periods (CT COSY). J Magn Reson Ser A. 1994;108(1):99–102.CrossRefGoogle Scholar
  54. 54.
    Zhang R, Ramamoorthy A. Constant-time 2D and 3D through-bond correlation NMR spectroscopy of solids under 60 kHz MAS. J Chem Phys. 2016;144(3):034202.CrossRefGoogle Scholar
  55. 55.
    Kotler SA, Brender JR, Vivekanandan S, Suzuki Y, Yamamoto K, Monette M, et al. High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification. Sci Rep. 2015;5:11811.CrossRefGoogle Scholar
  56. 56.
    Mroue KH, Nishiyama Y, Kumar Pandey M, Gong B, McNerny E, Kohn DH, et al. Proton-detected solid-state NMR spectroscopy of bone with ultrafast magic angle spinning. Sci Rep. 2015;5:11991.CrossRefGoogle Scholar
  57. 57.
    Nishiyama Y, Lu X, Trébosc J, Lafon O, Gan Z, Madhu PK, et al. Practical choice of 1H–1H decoupling schemes in through-bond 1H–{X} HMQC experiments at ultra-fast MAS. J Magn Reson. 2012;214:151–8.CrossRefGoogle Scholar
  58. 58.
    Ishii Y. 13C–13C dipolar recoupling under very fast magic angle spinning in solid-state nuclear magnetic resonance: applications to distance measurements, spectral assignments, and high-throughput secondary-structure determination. J Chem Phys. 2001;114(19):8473–83.CrossRefGoogle Scholar
  59. 59.
    Zhang R, Ramamoorthy A. Dynamics-based selective 2D 1H/1H chemical shift correlation spectroscopy under ultrafast MAS conditions. J Chem Phys. 2015;142(20):204201.CrossRefGoogle Scholar
  60. 60.
    Chattah AK, Zhang R, Mroue KH, Pfund LY, Longhi MR, Ramamoorthy A, et al. Investigating albendazole desmotropes by solid-state NMR spectroscopy. Mol Pharm. 2015;12(3):731–41.CrossRefGoogle Scholar
  61. 61.
    Zhang R, Pandey MK, Nishiyama Y, Ramamoorthy A. A novel high-resolution and sensitivity-enhanced three-dimensional solid-state NMR experiment under ultrafast magic angle spinning conditions. Sci Rep. 2015;5:11810.CrossRefGoogle Scholar
  62. 62.
    Zhang R, Mroue KH, Ramamoorthy A. Proton chemical shift tensors determined by 3D ultrafast MAS double-quantum NMR spectroscopy. J Chem Phys. 2015;143(14):144201.CrossRefGoogle Scholar
  63. 63.
    Hou G, Paramasivam S, Yan S, Polenova T, Vega AJ. Multidimensional magic angle spinning NMR spectroscopy for site-resolved measurement of proton chemical shift anisotropy in biological solids. J Am Chem Soc. 2013;135(4):1358–68.CrossRefGoogle Scholar
  64. 64.
    Pandey MK, Malon M, Ramamoorthy A, Nishiyama Y. Composite-180° pulse-based symmetry sequences to recouple proton chemical shift anisotropy tensors under ultrafast MAS solid-state NMR spectroscopy. J Magn Reson. 2015;250:45–64.CrossRefGoogle Scholar
  65. 65.
    Nishiyama Y, Kobayashi T, Malon M, Singappuli-Arachchige D, Slowing II, Pruski M. Studies of minute quantities of natural abundance molecules using 2D heteronuclear correlation spectroscopy under 100 kHz MAS. Solid State Nucl Magn Reson. 2015;66–67:56–61.CrossRefGoogle Scholar
  66. 66.
    Nishiyama Y, Malon M, Potrzebowski M, Paluch P, Amoureux J. Accurate NMR determination of C–H or N–H distances for unlabeled molecules. Solid State Nucl Magn Reson. 2016;73:15–21.Google Scholar
  67. 67.
    Zhang R, Damron J, Vosegaard T, Ramamoorthy A. A cross-polarization based rotating-frame separated-local-field NMR experiment under ultrafast MAS conditions. J Magn Reson. 2015;250:37–44.CrossRefGoogle Scholar
  68. 68.
    Zhang R, Nishiyama Y, Ramamoorthy A. Proton-detected 3D 1H/13C/1H correlation experiment for structural analysis in rigid solids under ultrafast-MAS above 60 kHz. J Chem Phys. 2015;143(16):164201.CrossRefGoogle Scholar
  69. 69.
    Nishiyama Y, Malon M, Ishii Y, Ramamoorthy A. 3D 15N/15N/1H chemical shift correlation experiment utilizing an RFDR-based 1H/1H mixing period at 100 kHz MAS. J Magn Reson. 2014;244(244):1–5.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Medicinal Chemical BiologyNankai UniversityTianjinP. R. China
  2. 2.Biophysics Program and Department of ChemistryThe University of MichiganAnn ArborUSA
  3. 3.Key Laboratory of Functional Polymer Materials of Ministry of Education and College of ChemistryNankai UniversityTianjinP. R. China

Personalised recommendations