skip to main content

Explore Research Products in the NSF-PAR

Title: 3D relaxation-assisted separation of wideline solid-state NMR patterns for achieving site resolution
There are currently no methods for the acquisition of ultra-wideline (UW) solid-state NMR spectra under static conditions that enable reliable separation and resolution of overlapping powder patterns arising from magnetically distinct nuclei. This stands in contrast to the variety of techniques available for spin-1/2 or half-integer quadrupolar nuclei with narrow central transition patterns under magic-angle spinning (MAS). Resolution of overlapping signals is routinely achieved in MRI and solution-state NMR by exploiting relaxation differences between nonequivalent sites. Preliminary studies of relaxation assisted separation (RAS) for separating overlapping UWNMR patterns using pseudo-inverse Laplace Transforms have reported two-dimensional spectra featuring relaxation rates correlated to NMR interaction frequencies. However, RAS methods are inherently sensitive to experimental noise, and require that relaxation rates associated with overlapped patterns be significantly different from one another. Herein, principal component analysis (PCA) denoising is implemented to increase the signal-to-noise ratios of the relaxation datasets and RAS routines are stabilized with truncated singular value decomposition (TSVD) and elastic net (EN) regularization to resolve overlapped patterns with a larger tolerance for differences in relaxation rates. We extend these methods for improved pattern resolution by utilizing 3D frequency- R 1 – R 2 correlation spectra. Synthetic and experimental datasets, including 35 Cl ( I = 3/2), 2 H ( I = 1), and 14 N ( I = 1) NMR of organic and biological compounds, are explored with both regularized 2D RAS and 3D RAS; comparison of these data reveal improved resolution in the latter case. These methods have great potential for separating overlapping powder patterns under both static and MAS conditions.  more » « less
Award ID(s):
2003854
NSF-PAR ID:
10341387
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Physical Chemistry Chemical Physics
Volume:
24
Issue:
37
ISSN:
1463-9076
Page Range / eLocation ID:
22792 to 22805
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ( , Magnetic Resonance in Chemistry)
    Abstract

    Solid‐state NMR (SSNMR) spectroscopy of integer‐spin quadrupolar nuclei is important for the molecular‐level characterization of a variety of materials and biological solids; of the integer spins,2H (S = 1) is by far the most widely studied, due to its usefulness in probing dynamical motions. SSNMR spectra of integer‐spin nuclei often feature very broad powder patterns that arise largely from the effects of the first‐order quadrupolar interaction; as such, the acquisition of high‐quality spectra continues to remain a challenge. The broadband adiabatic inversion cross‐polarization (BRAIN‐CP) pulse sequence, which is capable of cross‐polarization (CP) enhancement over large bandwidths, has found success for the acquisition of SSNMR spectra of integer‐spin nuclei, including14N (S = 1), especially when coupled with Carr–Purcell/Meiboom–Gill pulse sequences featuring frequency‐swept WURST pulses (WURST‐CPMG) forT2‐based signal enhancement. However, to date, there has not been a systematic investigation of the spin dynamics underlying BRAIN‐CP, nor any concrete theoretical models to aid in its parameterization for applications to integer‐spin nuclei. In addition, the BRAIN‐CP/WURST‐CPMG scheme has not been demonstrated for generalized application to wideline or ultra‐wideline (UW)2H SSNMR. Herein, we provide a theoretical description of the BRAIN‐CP pulse sequence for spin‐1/2 → spin‐1 CP under static conditions, featuring a set of analytical equations describing Hartmann–Hahn matching conditions and numerical simulations that elucidate a CP mechanism involving polarization transfer, coherence exchange, and adiabatic inversion. Several experimental examples are presented for comparison with theoretical models and previously developed integer‐spin CP methods, demonstrating rapid acquisition of2H NMR spectra from efficient broadband CP.

     
    more » « less
  2. ; ; ; ; ; ; ( , Phys. Chem. Chem. Phys.)
    We demonstrate that natural isotopic abundance 2D heteronuclear correlation (HETCOR) solid-state NMR spectra can be used to significantly reduce or eliminate the broadening of 1 H and 13 C solid-state NMR spectra of organic solids due to anisotropic bulk magnetic susceptibility (ABMS). ABMS often manifests in solids with aromatic groups, such as active pharmaceutical ingredients (APIs), and inhomogeneously broadens the NMR peaks of all nuclei in the sample. Inhomogeneous peaks with full widths at half maximum (FWHM) of ∼1 ppm typically result from ABMS broadening and the low spectral resolution impedes the analysis of solid-state NMR spectra. ABMS broadening of solid-state NMR spectra has previously been eliminated using 2D multiple-quantum correlation experiments, or by performing NMR experiments on diluted materials or single crystals. However, these experiments are often infeasible due to their poor sensitivity and/or provide limited gains in resolution. 2D 1 H– 13 C HETCOR experiments have previously been applied to reduce susceptibility broadening in paramagnetic solids and we show that this strategy can significantly reduce ABMS broadening in diamagnetic organic solids. Comparisons of 1D solid-state NMR spectra and 1 H and 13 C solid-state NMR spectra obtained from 2D 1 H– 13 C HETCOR NMR spectra show that the HETCOR spectrum directly increases resolution by a factor of 1.5 to 8. The direct gain in resolution is determined by the ratio of the inhomogeneous 13 C/ 1 H linewidth to the homogeneous 1 H linewidth, with the former depending on the magnitude of the ABMS broadening and the strength of the applied field and the latter on the efficiency of homonuclear decoupling. The direct gains in resolution obtained using the 2D HETCOR experiments are better than that obtained by dilution. For solids with long proton longitudinal relaxation times, dynamic nuclear polarization (DNP) was applied to enhance sensitivity and enable the acquisition of 2D 1 H– 13 C HETCOR NMR spectra. 2D 1 H– 13 C HETCOR experiments were applied to resolve and partially assign the NMR signals of the form I and form II polymorphs of aspirin in a sample containing both forms. These findings have important implications for ultra-high field NMR experiments, optimization of decoupling schemes and assessment of the fundamental limits on the resolution of solid-state NMR spectra. 
    more » « less
  3. ; ( , Journal of Biomolecular NMR)
    Abstract

    Selective stable isotope labeling has transformed structural and dynamics analysis of RNA by NMR spectroscopy. These methods can remove13C-13C dipolar couplings that complicate13C relaxation analyses. While these phenomena are well documented for sites with adjacent13C nuclei (e.g. ribose C1′), less is known about so-called isolated sites (e.g. adenosine C2). To investigate and quantify the effects of long-range (> 2 Å)13C-13C dipolar interactions on RNA dynamics, we simulated adenosine C2 relaxation rates in uniformly [U-13C/15N]-ATP or selectively [2-13C]-ATP labeled RNAs. Our simulations predict non-negligible13C-13C dipolar contributions from adenosine C4, C5, and C6 to C2 longitudinal (R1) relaxation rates in [U-13C/15N]-ATP labeled RNAs. Moreover, these contributions increase at higher magnetic fields and molecular weights to introduce discrepancies that exceed 50%. This will become increasingly important at GHz fields. Experimental R1measurements in the 61 nucleotide human hepatitis B virus encapsidation signal ε RNA labeled with [U-13C/15N]-ATP or [2-13C]-ATP corroborate these simulations. Thus, in the absence of selectively labeled samples, long-range13C-13C dipolar contributions must be explicitly taken into account when interpreting adenosine C2 R1rates in terms of motional models for large RNAs.

     
    more » « less
  4. ; ( , Magnetochemistry)
    The objective of spectral analysis is to resolve and extract relevant features from experimental data in an optimal fashion. In continuous-wave (cw) electron spin resonance (ESR) spectroscopy, both g values of a paramagnetic center and hyperfine splitting (A) caused by its interaction with neighboring magnetic nuclei in a molecule provide important structural and electronic information. However, in the presence of g- and/or A-anisotropy and/or large number of resonance lines, spectral analysis becomes highly challenging. Either high-resolution experimental techniques are employed to resolve the spectra in those cases or a range of suitable ESR frequencies are used in combination with simulations to identify the corresponding g and A values. In this work, we present a wavelet transform technique in resolving both simulated and experimental cw-ESR spectra by separating the hyperfine and super-hyperfine components. We exploit the multiresolution property of wavelet transforms that allow the separation of distinct features of a spectrum based on simultaneous analysis of spectrum and its varying frequency. We retain the wavelet components that stored the hyperfine and/or super-hyperfine features, while eliminating the wavelet components representing the remaining spectrum. We tested the method on simulated cases of metal–ligand adducts at L-, S-, and X-band frequencies, and showed that extracted g values, hyperfine and super-hyperfine coupling constants from simulated spectra, were in excellent agreement with the values of those parameters used in the simulations. For the experimental case of a copper(II) complex with distorted octahedral geometry, the method was able to extract g and hyperfine coupling constant values, and revealed features that were buried in the overlapped spectra. 
    more » « less
  5. ; ; ; ; ( , Magnetic Resonance in Chemistry)
    Abstract

    Detecting proximities between nuclei is crucial for atomic‐scale structure determination with nuclear magnetic resonance (NMR) spectroscopy. Different from spin‐1/2 nuclei, the methodology for quadrupolar nuclei is limited for solids due to the complex spin dynamics under simultaneous magic‐angle spinning (MAS) and radio‐frequency irradiation. Herein, the performances of several homonuclear rotary recoupling (HORROR)‐based homonuclear dipolar recoupling sequences are evaluated for27Al (spin‐5/2). It is shown numerically and experimentally on mesoporous alumina thatoutperforms the supercycled S3sequence and its pure double‐quantum (DQ) (bracketed) version, [S3], both in terms of DQ transfer efficiency and bandwidth. This result is surprising since the S3sequence is among the best low‐power recoupling schemes for spin‐1/2. The superiority ofis thoroughly explained, and the crucial role of radio‐frequency offsets during its spin dynamics is highlighted. The analytical approximation of, derived in an offset‐toggling frame, clarifies the interplay between offset and DQ efficiency, namely, the benefits of off‐resonance irradiation and the trough in DQ efficiency forwhen the irradiation is central between two resonances, both for spin‐1/2 and half‐integer‐spin quadrupolar nuclei. Additionally, density matrix propagations show that thesequence, applied to quadrupolar nuclei subject to quadrupolar interaction much larger than radio‐frequency frequency field, can create single‐ and multiple‐quantum coherences for near on‐resonance irradiation. This significantly perturbs the creation of DQ coherences between central transitions of neighboring quadrupolar nuclei. This effect explains the DQ efficiency trough for near on‐resonance irradiation, in the case of both cross‐correlation and autocorrelation peaks. Overall, this work aids experimental acquisition of homonuclear dipolar correlation spectra of half‐integer‐spin quadrupolar nuclei and provides theoretical insights towards improving recoupling schemes at high magnetic field and fast MAS.

     
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email