1.5 GHz (36 T) Series Connected Hybrid (SCH) NMR Spectroscopy

Biomedical NMR Research Beyond the Reach of Conventional NMR Magnets (Low-Temperature Superconductors)

Principal Investigator: Robert Schurko
Program Director: Zhehong Gan

Significant increases in field strength have led to new frontiers in the scientific arenas approachable by NMR spectroscopy. The Series Connected Hybrid (SCH) magnet, at a field of 36T, provides a view into the future for NMR spectroscopy; a future in which High Temperature Superconducting (HTS) magnets will have the potential for doubling the field strengths of current Low-Temperature Superconducting (LTS) magnets. The SCH magnet is a hybrid magnet having an outer superconducting coil of 13T and inner stacks of Bitter plates. The SCH magnet is the highest homogeneity and the highest stability resistive magnet that has been constructed, and it is used to collect high quality NMR data through the development of additional technology, using a cross section of scientists committed to developing and pushing the scientific frontiers of NMR spectroscopy at a field strength that is more than 50% higher than any other NMR spectrometer in the world. This technology included field stabilization with active feedback correction, a suite of NMR probes enabling solid state and solution NMR spectroscopy at 1H up to 1.5 GHz, and the development of new pulse sequences which capitalize on the advantages of high field.

  • Aim 1: Achieving High Homogeneity and High Stability in the 35.2 T SCH magnet (36T-SCH).  We will continue to work on the development of cascade field-regulation technology that takes advantage of an inductive pickup coil as well as NMR measurements to provide a feedback field correction, with an aim of achieving 0.1 ppm resolution, which will greatly benefit high-resolution multidimensional and oriented sample SSNMR studies of spin-1/2 nuclei (i.e., 1H, 13C, 15N) in biological systems.
  • Aim 2: NMR of Quadrupolar Nuclei at 35.2 T (36T-SCH).  The central-transition (CT, +1/2 ↔︎ –1/2) patterns of half-integer quadrupolar nuclei (HIQN, nuclear spin I = 3/2, 5/2, 7/2, or 9/2), which constitute 73% of NMR-active nuclei, are ideally acquired at UHFs, since their breadths narrow as B0–1. The development of methods for acquiring SSNMR spectra of maximal quality will continue, along with numerous applications to HIQN in biological systems, including metal atoms in proteins and biomaterials (see also Aim 3). A major focus will be upon the development of 17O enrichment schemes and concomitant SSNMR methods, with an aim of standardizing 17O SSNMR investigations of large biological molecules, which will provide a new and exciting means of studying their structure and functionality.
  • Aim 3: Static SSNMR of Quadrupolar Nuclei at 28.2 T (32T-SCM).  New low-temperature static (i.e., stationary samples) SSNMR probes will be developed for the all-HTS 32T-SCM platform, which due to its cold bore, allows easy access to a temperature range from sub-4 K to 30 K, and for NMR operation at 28.2 T. This platform will be dedicated to the investigation of HIQN in biological molecules (especially metal sites in proteins and biomaterials, e.g., 25Mg, 43Ca, 65Cu, 67Zn), and rely upon the development and application of pulse sequences for the acquisition of ultra-wideline (UW) NMR spectra at very low temperatures (i.e., huge Boltzmann enhancements occur from 4-30 K that lead to signal increases of two orders of magnitude).   
  • Aim 4: Fast MAS of Biological Systems at Fields up to 35.2 T (36T-SCH, 800#1, 800#2). Fast magic-angle spinning (FMAS) is revolutionizing biological ssNMR via 1H indirect detection (ID) methods, showing great potential for the characterization of proteins. The resolution of 1H ID ssNMR spectra greatly benefit from the combination of new FMAS NMR probe technologies and UHFs, which enhance sensitivity, dispersion, and resolution, and reduce homonuclear 1H-1H dipolar coupling effects on peak widths.  We will develop new probe technologies that offer signal enhancements of greater than a factor of two over commercially available probes and 1H-detected HMQC methods to facilitate the investigation of HIQN in proteins such as 17O; this will expand the frontiers of characterizations of structure and dynamics in proteins.
  • Aim 5: Enhanced OS SSNMR of Membrane Proteins (36T-SCH, 800#1, 800#2). Currently, the only technology for accurately determining the orientation of membrane proteins in a lipid bilayer is oriented sample (OS) ssNMR. We will exploit the sensitivity enhancements associated with UHFs, and enhanced molecular alignments that further reduce peak widths, to carry out 13C and 15N ssNMR studies of OSs. We will also pursue 17O OS ssNMR investigations of proteins that have never before been attempted, focusing on the crucial hydrogen bonding interactions between proteins, water, and a variety of cations.

Associated Driving Biomedical Projects (DBPs):

  • Structural and proton dynamics of pyridoxal-5′-phosphate dependent enzymes; Leonard Mueller, UC Riverside
  • Molecular organization and drug responses of fungal cell walls; Tuo Wang, Louisiana State University
  • Mechanism of ion (non)selectivity in NaK channels; Katherine Henzler-Wildman, University of Wisconsin-Madison
  • Structural features of the alum-based vaccine adjuvants and interactions with the antigens by 27Al ssNMR; Moreno Lelli, Center for Magnetic Resonance (CERM), University of Florence, Italy
  • Mechanism of membrane protein efflux pumps in multidrug resistance; Nate Traaseth, New York University

Associated Collaboration & Service Projects (CSPs):

  • Structure and Dynamics of Self-Assembled biomolecules: Fast MAS of RSV (Respiratory Synctial Virus) and amyloid proteins; Bo Chen, University of Central Florida
  • Identification of interfacial bonding environments in functional nanomaterials and biomaterials using high resolution solid state NMR at (ultra)-high fields; Christian Bonhomme, University of Sorbonne, France
  • Fast MAS of amyloid proteins: Cytotoxic Transthyretin Oligomers and their Interaction with Membranes, Kwang Hun Lim, East Carolina University
  • Membrane protein effectors of pathogen interactions with host; Francesca Marassi, Sanford Burnham Prebys Medical Discovery Institute
  • Investigating hereditary and UV light-related aggregation of eye lens proteins; Rachel Martin, UC Irvine
  • Probing Zn chemistry in metalloenzymes, Robert McKenna, University of Florida
  • Protein molecular structure, conformational dynamics, and inter-protein interactions in human health and disease, Dylan Murray, University of California, Davis
  • Dynamic Nuclear Polarization of Membrane Proteins in Lipid Bilayers by Solid-State NMR, Alex Nevzorov, North Carolina State University
  • Structural Studies of FMN domain interactions with cytochrome-P450; Ayyalusamy Ramamoorthy, University of Michigan
  • NMR Structural Analysis of Calcium Regulation in Muscle; Gianluigi Veglia, University of Minnesota 
  • Dynamic structures of lipid-membrane protein complexes via ssNMR; Benjamin Wylie, Texas Tech University 

Technology Partnership Projects (TPPs)

  • A fast quad-res HCNO 100 kHz MAS probe for 17O ssNMR of proteins; Robert Griffin, Massachusetts Institute of Technology
  • Development of an HX broadband low-γ NMR probe for the 32T-SCM, Arneil Reyes, NHMFL, DC Field Facility
  • Mechanochemical methods for 17O-enrichment of amino acids; Danielle Laurencin, Institut Charles Gerhardt, University of Montpellier, France
  • Synthesis of 13C,17O-labeled proteins and their study by 17O ssNMR; Gang Wu, Queen’s University, Kingston, Ontario, Canada

To inquire about starting a collaboration including establishing a DBP, CSP, or TPP, please contact principal investigators for this TDP: https://nmrprobe.org/people/leadership/.