Solid-state NMR characterization of the molecular conformation in disordered methyl α-L-rhamnofuranoside.

TL;DR: A concerted rearrangement of OH hydrogens is proposed to account for the observed dynamic disorder in disordered methyl α-L-rhamnofuranoside and the relatively minor differences in non-hydrogen atom positions suggest that characterization of a complete crystal structure by X-ray powder diffraction may be feasible.

Abstract: A combination of solid-state 13C NMR tensor data and DFT computational methods is utilized to predict the conformation in disordered methyl α-l-rhamnofuranoside. This previously uncharacterized solid is found to be crystalline and consists of at least six distinct conformations that exchange on the kHz time scale. A total of 66 model structures were evaluated, and six were identified as being consistent with experimental 13C NMR data. All feasible structures have very similar carbon and oxygen positions and differ most significantly in OH hydrogen orientations. A concerted rearrangement of OH hydrogens is proposed to account for the observed dynamic disorder. This rearrangement is accompanied by smaller changes in ring conformation and is slow enough to be observed on the NMR time scale due to severe steric crowding among ring substituents. The relatively minor differences in non-hydrogen atom positions in the final structures suggest that characterization of a complete crystal structure by X-ray powder d...

Summary

Introduction.

• For the past century the insights provided by crystallography have help guide the development of science in a remarkably wide range of disciplines.
• A key early development in the pursuit of crystal structure by NMR was the ability to characterize molecular conformation by solid-state NMR.
• Many materials form solids containing molecules that are partially disordered or that consist of mixtures of several lattice types (i.e. mixed phase materials).
• Conformational characterization for each unique structure in these solids is valuable because such structures provide the initial models needed for crystal structure determination by powder diffraction methods.
• Accordingly, the aim of the present study is to characterize the molecular conformations of one such disordered solid, namely, methyl α-L-rhamnofuranoside .

Experimental and Theoretical Methods.

• Hz per point was obtained in the acquisition dimension.
• Of equal importance, the C2 13 C tensor data computed using this conformation was found to agree well with experimental data.
• To further establish conformations, all combinations of conformations about C4-O, C5-C6 and C6-O had to be considered because none can be considered isolated from the other sites.
• Overall, this process required consideration of 66 conformations rather than the 243 structures that would have been evaluated if isolated regions had not been utilized.

Characterizing disorder.

• Such NMR spectra can arise from either static or dynamic disorder of the individual molecules.
• Fortunately, solids with Z' > 1 can usually be distinguished from disordered materials since they contain resonances that are relatively insensitive to temperature variations and that occur in approximately 1:1 ratios.
• The disorder was found to be dynamic based upon spectra acquired over a range of spinning speeds from 2.3 -4.8 kHz .
• In these experiments, the number of resonances per position was found to vary with spinning speed.
• This result is consistent with conformational exchanges that occur at rates comparable to the spinning speed with significant differences observed at C2, C3, C4, and C8.

Assignment of 1 H and 13 C chemical shifts.

• Accurate structural studies require that all chemical shifts be correctly assigned to the corresponding nuclei.
• 14 Since these assignments were based exclusively on 1D data, new solution phase analyses were performed to verify all assignments.
• These new data were conducted in CD 3 OD and rely primarily on DQF-COSY data (see experimental).
• All assignments and important DQF-COSY correlations are listed in Table 1 .
• All chemical shift assignments in solid methyl α-L-rhamnofuranoside were made by comparison to those in solution.

Conformational predictions.

• Prior work has demonstrated that accurate conformations can be predicted from 13 C chemical shift tensor information.
• In disordered samples, comparison between experimental and calculated tensor shift values is challenging because multiple resonances are observed for each 13 C site in the molecule and identifying one particular set of lines arising from a single conformation can be difficult.
• Thus, most of the experimental values for a given position display differences less than the error in the calculated values.
• When each of these experimental datasets was compared to the model structures, six conformations were found to be compatible with the experimental data.
• The structures selected show that the disorder in methyl α-L-rhamnofuranoside consists primarily of disorder in hydrogen positions.

Conclusions.

• Solid-state NMR 13 C tensor data are paired with computational methods to establish molecular conformation in a small carbohydrate that is dynamically disordered in the solid state and unsuitable for conventional single crystal diffraction techniques.
• The solid consists of at least six conformations that interconvert on the kHz timescale.
• An evaluation of dozens of candidate structures by computational methods identifies six conformations that are consistent with the NMR data.
• These structures differ primarily at OH hydrogen positions with heavier atoms exhibiting only minor differences that appear to arise from changes in ring conformation that accompany the OH hydrogen reorientations.
• This study serves to define the structure in the crystallographic asymmetric unit and to identify favorable intramolecular hydrogen bonding arrangements.

Figures

Table 2. The 13C principal value chemical shifts (ppm) for solid methyl α–L– rhamnofuranoside.

Figure 5. A wide variety of molecular conformations were initially evaluated (left). Of these, six structures (right) were found to be compatible with all 13C shift tensor principal values data.

Table 1. Proton and 13C chemical shift assignments (ppm) for methyl α–L– rhamnofuranoside.

Figure 1. Schematic of methyl α–L–rhamnofuranoside including the numbering used herein.

Figure 4. The FIREMAT data from carbon 2 illustrating the high resolution and signalto-noise data obtained from the analysis. All other positions provided comparable high quality data.

Table 5. Hydrogen bonds found in the six model structures agreeing with 13C NMR tensor data.

Figure 2. The 13C CP/MAS spectrum of methyl α–L–rhamnofuranoside. Each atomic position displays multiple resonances, reflecting the dynamic disorder present in the powder. As many as six resonances are observed for each carbon, indicating the presence of six rapidly interconverting conformations in the solid. Regions of the spectrum containing no resonances have been omitted.

Table 4. Conformational descriptors of the six model structures agreeing with 13C chemical shift tensor principal values.

Figure 6. All conformations of methyl α–L–rhamnofuranoside evaluated are shown with hydrogen atoms included in the left figure. Those conformations consistent with the 13C chemical shift tensor data are shown at the right. The structures retained as feasible (right) can be seen to differ most significantly in OH hydrogen positions and are thought to interconvert via a concerted OH reorientation.

Table 3. The averaged 13C NMR shift tensor principal values used for comparison with calculated model structures.

Figure 3. A comparison of 13C CP/MAS spectra of methyl α–L–rhamnofuranoside acquired at four spinning speeds. The changes in the spectra are consistent with dynamic disorder in the kHz range. The C7 methyl resonance is omitted to allow splitting at other frequencies to be more clearly observed.

Figure 7. A comparison of the four ring conformations found to agree with 13C tensor principal value data. The 5E and 3T4 structures consist of two superimposed conformations that differ primarily in the OH orientation at C6.

Full text

http://www.diva-portal.org
Preprint
This is the submitted version of a paper published in Journal of Physical Chemistry A.
Citation for the original published paper (version of record):
Harper, J K., Tishler, D., Richardson, D., Lokvam, J., Pendrill, R. et al. (2013)
Solid-State NMR Characterization of the Molecular Conformation in Disordered Methyl alpha-
L-Rhamnofuranoside.
Journal of Physical Chemistry A, 117(26): 5534-5541
http://dx.doi.org/10.1021/jp4036666
Access to the published version may require subscription.
N.B. When citing this work, cite the original published paper.
Permanent link to this version:
http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-92801

1
Solid-state NMR Characterization of Molecular Conformation in Disordered Methyl α–
L–rhamnofuranoside.
James K. Harper,*
a
Derek Tishler,
b
David Richardson,
a
John Lokvam,
c
Robert Pendrill,
d
Göran Widmalm.
d
a
University of Central Florida, Department of Chemistry, 4000 Central Florida Blvd.,
Orlando, FL 32816, USA.
b
University of Central Florida, Department of Physics, Orlando, FL 32816, USA.
c
University of California Berkeley, Department of Biology, Berkeley, CA 94720, USA.
d
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106
91, Stockholm, Sweden.

2
Solid-state NMR Characterization of Molecular Conformation in Disordered Methyl α–
L–rhamnofuranoside.
Abstract.
A combination of solid-state
13
C NMR tensor data and DFT computational
methods are utilized to predict conformation in disordered methyl α–L–
rhamnofuranoside. This previously uncharacterized solid is found to be crystalline and
consists of at least six distinct conformations that exchange on the kHz timescale. A total
of 66 model structures were evaluated and six were identified as being consistent with
experimental
13
C NMR data. All feasible structures have very similar heavy atom
positions and differ most significantly in OH hydrogen orientations. A concerted
rearrangement of OH hydrogens is proposed to account for the observed dynamic
disorder. This rearrangement is accompanied by smaller changes in ring conformation
and is slow enough to be observed on the NMR timescale due to severe steric crowding
among ring substituents. The relatively minor heavy atom differences in the final
structures suggest that characterization of a complete crystal structure by x-ray powder
diffraction may be feasible.
Keywords.
13
C tensor principal values, NMR crystallography.

3
Introduction.
For the past century the insights provided by crystallography have help guide the
development of science in a remarkably wide range of disciplines. Several well-
established diffraction techniques are now available for determining structure in materials
that form crystals and, to a lesser extent, microcrystalline powders. Recently, the
methods of solid-state NMR have been directed toward the problem of crystallographic
characterization and the prospect of performing “NMR crystallography” has become
feasible.
1
Presently, most NMR crystallographic studies emphasize the NMR
characterization of the molecular structure of an individual molecule or the repeating unit
in framework materials.
2
The longer-range lattice order needed to identify a space group
is usually obtained independently from x-ray powder diffraction methods that rely on the
NMR determined structure as a starting model. However, alternative methods
3
including
theoretical crystal structure prediction methods have also been found to be capable of
also providing the lattice structure.
2b,4
Crystallographic analysis by NMR spectroscopy is appealing because NMR is
capable of characterizing a diverse variety of solids that can be difficult to treat by
conventional diffraction methods. A key early development in the pursuit of crystal
structure by NMR was the ability to characterize molecular conformation by solid-state
NMR.
5
Such structural characterizations can now be achieved using a variety of methods
and have been used to elucidate structure in proteins,
6
inorganic materials
2a,2b,2h,2i,2l,2m
and
smaller organic molecules.
7
Presently, these studies have largely been limited to well-
ordered crystalline solids and extension to more challenging materials is desirable. For
example, many materials form solids containing molecules that are partially disordered or

4
that consist of mixtures of several lattice types (i.e. mixed phase materials). In these
cases NMR has the potential to provide molecular conformation for each unique structure
found in the solid because several resonances are usually observed for each atomic
position due to the multiple distinct conformations present in the solid.
Solid-state NMR is remarkably sensitive to even minor differences in structure
and such variations, when present, often result in new resonances for a given site. Thus,
disordered or mixed phase solids usually exhibit several resonances for each atom in the
molecule. Conformational characterization for each unique structure in these solids is
valuable because such structures provide the initial models needed for crystal structure
determination by powder diffraction methods. Accordingly, the aim of the present study
is to characterize the molecular conformations of one such disordered solid, namely,
methyl α–L–rhamnofuranoside (Figure 1). Presently, there is no known crystal structure
for methyl α–L–rhamnofuranoside and this study will provide the structure of the
crystallographic asymmetric unit for each conformation present. Inspection of the
13
C
NMR spectrum of solid methyl α–L–rhamnofuranoside shows disorder at several of the
carbons and narrow lines characteristic of a crystalline solid. Here,
13
C tensor principal
values are measured for all sites. Assignment of conformation is accomplished using a
previously described approach
5a
that evaluates a wide variety of possible conformations
and retains structures having computed tensors that agree with experimental data.

Frequently asked questions

Q1. What are the contributions in this paper?

Chichester et al. this paper used solid-state NMR tensor data and computational methods to establish molecular conformation in a small carbohydrate that is dynamically disordered in the solid state and unsuitable for conventional single crystal diffraction techniques.