Rigid Orthogonal Bis-TEMPO Biradicals with Improved
Solubility for Dynamic Nuclear Polarization
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Citation
Dane, Eric L. et al. “Rigid Orthogonal Bis-TEMPO Biradicals with
Improved Solubility for Dynamic Nuclear Polarization.” The
Journal of Organic Chemistry 77.4 (2012): 1789–1797.
CrossRef. Web.
As Published
http://dx.doi.org/10.1021/jo202349j
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American Chemical Society
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Author's final manuscript
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Wed May 25 20:28:19 EDT 2016
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http://hdl.handle.net/1721.1/78309
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The Journal of Organic Chemistry
Rigid Orthogonal bis-TEMPO Biradicals with Improved
Solubility for Dynamic Nuclear Polarization
Journal:
Manuscript ID:
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Complete List of Authors:
The Journal of Organic Chemistry
jo-2011-02349j.R1
Article
n/a
Dane, Eric; Massachusetts Institute of Technology, Chemistry
Corzilius, Bjoern; MIT, Francis Bitter Magnet Lab
Rizzato, Egon; Università degli Studi di Bologna, Chimica Organica
"A. Mangini"
Stocker, Pierre; SREP LCP UMR 6264, Université d'Aix Marseille
Maly, Thorsten; Massachusetts Institute of Technology, Chemistry
Smith, Albert; MIT, Francis Bitter Magnet Lab
Griffin, Robert; Massachusetts Institute of Technology, Chemistry
Ouari, Olivier; SREP LCP UMR 6264, Université d'Aix Marseille
Tordo, Paul; SREP UMR LCP 6264, Universite d Aix Marseille,
Swager, Timothy; Mass. Inst. of Tech., Chemistry; Massachusetts
Institute of Technology, Department of Chemistry 18-597
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The Journal of Organic Chemistry
Rigid Orthogonal bis-TEMPO Biradicals with Improved
Solubility for Dynamic Nuclear Polarization
Eric L. Dane1, Björn Corzilius1, 2, Egon Rizzato3, Pierre Stocker4, Thorsten Maly1, 2, Albert A. Smith1, 2,
Robert G. Griffin1, 2, *, Olivier Ouari3,*, Paul Tordo3, , and Timothy M. Swager1,*
1
Department of Chemistry and 2Francis Bitter Magnet Laboratory, Massachusetts Institute of
Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 USA
3
Aix-Marseille Univ., LCP, 13397 Cédex 20, Marseille, France; CNRS LCP, 13397 Cédex 20,
Marseille, France 4Aix Marseille Univ., ISM2, 13397, Marseille, France; CNRS ISM2, 13397,
Marseille, France
EMAIL: tswager@mit.edu, rgg@mit.edu, olivier.ouari@univ-provence.fr
RECEIVED DATE (to be inserted):
TITLE RUNNING HEAD. Rigid orthogonal biradicals for DNP.
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TOC Graphic
Abstract
The synthesis and characterization of oxidized bis-thioketal-trispiro dinitroxide biradicals that orient
the nitroxides in a rigid, approximately orthogonal geometry is reported. The biradicals show better
performance as polarizing agents in dynamic nuclear polarization (DNP) NMR experiments as
compared to biradicals lacking the constrained geometry. In addition, the biradicals display improved
solubility in aqueous media due to the presence of polar sulfoxides. The results suggest that the
orientation of the radicals is not dramatically affected by the oxidation state of the sulfur atoms in the
biradical, and we conclude that a biradical polarizing agent containing a mixture of oxidation states can
be used for improved solubility without a loss in performance.
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Introduction
Nuclear magnetic resonance (NMR) is well established as an indispensible tool to the modern organic
chemist1 and in recent years it has also become essential in many areas of biochemistry and structural
biology.2,3,4 Furthermore, magic angle spinning (MAS) NMR has emerged as the method of choice in
studies of polypeptides and proteins that are not amenable to X-ray crystallography or solution NMR
methods, such as membrane proteins and amyloid fibers.5,6 However, MAS and many other NMR
experiments are often limited by sensitivity, especially when multidimensional experiments on 13C and
15
N are of interest.7 Dynamic nuclear polarization (DNP) offers an approach to address this problem by
transferring the greater spin polarization of electrons to nuclei.8
In particular, gyrotron-based,
microwave-driven DNP9,10 using stable organic biradicals as the source of unpaired electrons is a
technique that significantly increases the signal-to-noise (S/N) ratio in MAS NMR spectra, therefore
enabling the use of less sample and shorter acquisition times.11-13 Implementation of DNP experiments
requires that high frequency microwave instrumentation and probes are interfaced to conventional NMR
spectrometers.14,15 In addition, successful DNP experiments require nonperturbing exogenous or
endogeneous paramagnetic polarization agents that can be added to or are part of the sample.16,17 The
design and synthesis of a new class of biradical polarizing agents with the relative orientations of the
TEMPO moieties locked with respect to one another is the subject of this paper.18
We have demonstrated that stable organic biradicals, such as the bis-TEMPO biradical TOTAPOL
(Chart 1), are more efficient DNP polarizing agents than monomeric radicals, such as 4-amino-TEMPO,
because covalently tethering the two radicals results in greater electron-electron dipolar coupling at
lower radical concentration.16-19 This approach is preferable to the use of monoradicals because the high
concentration needed for intermolecular dipolar coupling leads to undesirable line-broadening in the
NMR spectra. Recently, Griffin, Tordo and coworkers,18 reported that a bis-TEMPO biradical (Chart 1,
bTbk) with a defined geometry that rigidly holds the two nitroxide moieties approximately orthogonal to
one another shows larger enhancements than TOTAPOL and other TEMPO biradicals under similar
conditions. A detailed description of why this orthogonal geometry is advantageous is in the
3
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literature.19,20 In brief, at high magnetic fields and in frozen solutions, the form of a nitroxide radical’s
signal is dominated by g-anisotropy, and only certain relative orientations of the two planes defined by
the g-tensors of the N-O groups provide the correct frequency difference between the two electrons to
optimize DNP via a three spin process (2 electrons, 1 nuclei) known as the cross effect (CE).19-24
Therefore, constraining the relative orientation of the radicals to a geometry favorable to the CE
optimizes the DNP efficiency. Accordingly, the biradical bTbk is the polarizing agent exhibiting the
highest DNP enhancement factor in MAS NMR. However, its sparse solubility in water/glycerol
mixtures limits its application in MAS experiments on proteins and MRI dissolution experiments25
which are among the major foci of contemporary DNP.
CHART 1.
To synthesize a more water-soluble dinitroxide biradical retaining the desirable orientation of bTbk,
we replaced the oxygen atoms with sulfur (Chart 1, Structure 1). Compounds containing the 2,4,8,10tetrathia[5.5]undecane skeleton have been previously reported, but in general have been less studied
than their oxygen counterparts.26-29 Oxidation of the sulfur atoms to sulfoxides and sulfones was
expected to introduce polar groups that promote solubility in polar solvents. Reports of oxidized 1,3ACS Paragon Plus Environment
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dithianes in the literature suggested that the compounds might have the desired solubility.30 We initially
chose to synthesize the tetrasulfone version of 1 (Scheme 1) because we anticipated that it would be
easier to characterize as compared to the intermediate oxidation products. Unfortunately, tetrasulfone 4
lacked the desired solubility in aqueous solutions. To address this issue, we synthesized biradicals with
the sulfur atoms oxidized to sulfoxides rather than sulfones because sulfoxides were anticipated to
provide better water solubility.31 We pursued two complimentary approaches to this problem. We
synthesized a pure sample of the disulfoxide (Scheme 2, 8) using a protecting group strategy and
chromatographic purification. Additionally, we synthesized a complex mixture of biradicals (1) in a
two-step procedure that did not require the use of protecting groups or chromatography. The DNP
performances of 1 and 8 were evaluated in MAS-DNP at 5T/140 GHz at 90 K in a mixture of
DMSO/water (60/40) and compared to bTbk and TOTAPOL.
Scheme 1. Synthesis of biradical 4.
Results and Discussion
Synthesis
The synthesis of biradical 4 began with the condensation of 1.0 equivalent of tetraacetyl
pentaerythrithiol32 with 2.0 equivalents of 2,2,6,6-tetramethyl-4-piperidone monohydrate in refluxing
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concentrated hydrochloric acid (Scheme 1). The bis-hydrochloride salt (2a) precipitated upon formation
and was easily isolated by filtration as a pure compound. For the oxidation of the thioethers to sulfones,
acidic conditions were used to ensure protonation of compound 2a and thereby protect against
competing oxidation of the amine. After investigating a variety of commonly used oxidants (such as
KMnO4,33 H2O2/AcOH,34,35 m-CPBA,36-39 Oxone,40,41 NaIO4,31 etc.), we found that only ruthenium
tetraoxide,42
generated in situ from RuCl3 and periodic acid, provided complete oxidation to the
tetrasulfone, albeit in moderate yield. Tetrasulfone 3 was isolated as the free base by extraction from
basic water. An X-ray crystal structure revealed intramolecular hydrogen bonds between the amine
protons and proximate sulfone oxygens (Scheme 1). Tetrasulfone 3 was further oxidized with 3.0 equiv
of m-chloroperbenzoic acid to form biradical 4.43
Biradical 4 showed excellent solubility in pure DMSO (>20 mM), but in a 60:40 mixture of
DMSO/H2O it was only sparingly soluble (< 2 mM). Sulfones are not known to be especially good at
imparting water solubility although they do contain polar sulfur-oxygen bonds.38 However, the lack of
water solubility observed for 4 may also be a consequence of the structural rigidity. Sulfoxides contain
sulfur-oxygen bonds that are significantly more polarized than those in sulfones, and in addition they
offer more opportunity for the solvent to interact with the electropositive sulfur atom as compared to
more sterically shielded sulfones.44 In addition, sulfoxides are chiral centers when the two carbon atoms
bonded to the sulfur are unsymmetrical because of the sulfoxide’s pyramidal geometry. Therefore, the
presence of a mixture of diastereomers would likely be beneficial for improving solubility.
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Scheme 2. Synthesis of biradicals 7 and 8.
To investigate the properties of the sulfoxide derivatives, a pure sample of sulfoxide dinitroxide 8 was
synthesized using a different synthetic strategy (Scheme 2). Due to the synthetic challenge in selectively
controlling the oxidation of the thioether to sulfoxide in the presence of reactive amine or nitroxide
groups, we protected the hydroxylamines as silyl ethers (Scheme 2). TBDMS protected-TEMPONE
was reacted with pentaerythrityl tetrathiol in the presence of BF3-Et2O in DCM and afforded 6 in a 75%
yield.
Hydrofluoric acid promoted deprotection of 6 led to the dinitroxide 7 in moderate yield.
Selective oxidation of 6 was achieved by m-CPBA (2.2 eq.) in Et2O and subsequent deprotection of the
aminoxyl groups by HF in acetonitrile led to disulfoxide dinitroxide 8 in 50% yield after
chromatographic purification. The corresponding tetrasulfoxide derivative was never attained when 4 or
more equivalents of m-CPBA, H2O2, NaIO4, or DMD were used as oxidant; instead, a mixture of
oxidation states (sulfoxide – sulfone) was observed. This result is in agreement with previous work
where it has been reported that oxidation of 1,3-dithiane to the monosulfoxide occurred rapidly but that
oxidation to the sulfone competed with oxidation of the second sulfide to the disulfoxide.38 The
structure of 8 was confirmed by 1HNMR (after reduction with phenylhydrazine), IR, and MS. Biradical
8 was soluble in DMSO, in 60:40 DMSO/H20 (20 mM), and in water (5 mM).
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Scheme 3. Oxidation of 2b to biradical 1.
The improved solubility of 8 supported our hypothesis that sulfoxides would be better at improving
solubility than sulfones. We were interested in investigating the solubility and DNP performance of the
intermediate oxidation states between the disulfoxide and the tetrasulfone, but the synthetic challenge of
generating and isolating all of the possible species was prohibitive. However, we surmised that by
synthesizing mixtures of these species we could gain some insight into their behavior. To generate these
mixtures, we performed the oxidation of 2b in three organic solvents (dichloromethane, benzene,
acetonitrile) with 7.1 equivalents of m-CPBA (3 equivalents to generate the two nitroxide radicals and 4
equivalents to oxidize the thioethers) as shown in Scheme 3. In order to generate a variety of mixtures,
organic solvents of different polarity (least polar, benzene; most polar, acetonitrile) were chosen with the
expectation that we would observe changes in the sulfoxide/sulfone selectivity of the oxidant.44 The
purification method was carefully designed to remove likely contaminants, because characterization of
complex mixtures is difficult. Extraction with acidic and basic aqueous solutions removed unreacted
amines and acidic groups (i.e. m-chlorobenzoic acid), respectively. Additionally, the reaction mixtures
were stirred in DCM partitioned with basic aqueous solution of the oxidant potassium ferricyanide to
ensure that any hydroxylamines were fully oxidized to nitroxides. Finally, the biradical mixture was
precipitated from a 1:2 solution of DCM/hexane to remove low polarity materials. The final products
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(1a-c) were isolated in moderate-to-low yield. The biradical mixtures were evaluated with proton NMR
before and after reduction with zinc powder in d4-methanol. Before reduction, at a concentration of 10
mg/mL (approximately 17 mM), only solvent signals were visible. After reduction, a series of singlets
became visible between 2.0 and 1.0 ppm, as expected. Molecules with a 2,4,8,10-tetrathia[5.5]undecane
skeleton have complex NMR spectra due the conformational flexibility of the rings, which adds to the
complexity inherent to a mixture of species.26 Based on IR, all three samples contained significant
amounts of both sulfoxides and sulfones (see Supporting Information, Figure S2). A comparison of
peak intensities indicates that 1a (CH2Cl2) has the largest ratio of sulfoxides to sulfones.
IR also
confirmed the presence of the nitroxide by observation of absorbances characteristic of the N-O bond at
1362 and 1235 cm-1. The extent and range of oxidation was evaluated using electrospray ionization
mass spectrometry (ESI-MS) (see Supporting Information, Figures S3-S5). Based on a qualitative
inspection of the ESI-MS spectra, 1a (CH2Cl2) and 1c (CH3CN) have an average of 4 oxygen atoms in
addition to the 2 oxygens of the nitroxide radicals. Whereas 1b appears to have an average of 5 oxygen
atoms in addition to the 2 oxygens of the nitroxide radicals.. Elemental analysis performed on sample
1a suggests an average of 4.5 sulfur-oxygen bonds per molecule, although the sulfur content was below
the expected value for proposed structure. All three samples (1a-c) were soluble at > 10 mM in 60:40
DMSO/H2O, but they were not appreciably soluble in 60:40 glycerol/H2O.
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Figure 1. Effect of sulfur oxidation on geometry. (A) Stick model of X-ray structure of biradical 7. (B)
Stick model of X-ray structure of biradical 4. (C) Equilibrium geometry model of the trans,transtetrasulfoxide version of biradical 1.
Analysis of Geometry
The X-ray crystal structures of 4 and 7 (Figure 1 A,B) show solid-state geometries wherein the
nitroxide moieties are held in the desired near orthogonal geometry, albeit with a larger N-to-N distance
primarily due to the increased length of the carbon-sulfur bonds as compared to carbon-oxygen bonds.
Based on analysis of the crystal structures, the nitrogen atoms of the nitroxides in 4 (N-to-N
distance,12.2 Å) are approximately 1.5 Å farther apart than the same atoms in bTbk (N-to-N distance,
10.7 Å). Similarly, in 7 (N-to-N distance, 12.1 Å) the nitrogen atoms are approximately 1.4 Å farther
apart as compared to bTbk.18 When the orthogonality of the biradicals is assessed based on the dihedral
angle between planes 1 and 2 in the X-ray crystal structures, an angle of 90.4° is measured for bTbk and
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a slightly larger angle of 93.6° is measured for biradical 4.
A significantly larger angle of 98.9° is
measured for 7.
The X-ray crystallographic analysis of 4 and 7 do not shed light on how the presence of sulfoxides or
both sulfoxides and sulfones would affect the geometry of derivatives. In order to investigate the impact
of the oxidation state of the sulfur atoms on the relative geometry of the nitroxide radicals we first
investigated how oxidation affects the carbon-sulfur-carbon bond angle in thioethers, sulfoxides, and
sulfones in 1,3-dithianes. An examination of the Cambridge Structural Database reveals that in 1,3dithiane structures the carbon-sulfur-carbon bond angles are similar for these three oxidation states, with
an average angle of 101.7 ± 1.4˚ in thioethers, 100.5± 1.7˚ in sulfoxides, and 102.6 ± 2.0˚ in sulfones
(thioether and sulfoxide angles were determined from structures that had tetrasubstituted carbons at the
2-position, whereas the sulfone angles came from structures without this constraint as a result of limited
examples, see Supporting Information, Figure S7). When the standard deviations are taken into account,
the differences in the average bonds angles are not statistically significant. Based on these results, it is
not clear what effect, if any, changing the oxidation state has on the biradical’s geometry.
To better
understand the effect of sulfur oxidation on the biradical’s geometry, we performed molecular
mechanics (MMFF94) calculations on biradical 8 and a series of compounds representing a range of
oxidation states of 1 (Supporting Information, Figure S1). The effect of oxidation on the orthogonal
geometry was evaluated by measuring the dihedral angle between the two planes (plane 1, plane 2)
formed by the three carbon atoms closest to the spiro-thioketal linkage in each nitroxide ring (Figure 1C,
green). The same minimizations were performed on bTbk, biradical 4, and biradical 7 and compared to
the values obtained from the XRCS in order to comment on the accuracy of the calculations. For bTbk,
the MM-minimized structure predicts a dihedral angle of 91.5°, which is in good agreement with the
angle of 90.4° measured from the XRCS.
In the case of biradical 4, the MM-minimized structure
predicts a dihedral angle of 92.5°, which is in good agreement with the angle of 93.6° measured from the
XRCS. In the case biradical 7, the predicted dihedral angle is 90.9°, which is significantly smaller than
the angle of 98.9° measured from the XRCS. This discrepancy may reflect the greater flexibility of the
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thioether linkages as compared to the sulfoxide or sulfone linkages. In all cases, the measured angle
from the calculated structures was within a range of 90˚ ± 6, suggesting that the effect of the sulfur
oxidation state on the orthogonal geometry between the nitroxide rings is minimal within the structures
studied.
Figure 2. 9 GHz EPR spectra of biradical 4. (A) Room temperature liquid-state EPR spectra of 1 mM
biradical 4 in DMSO/H2O (50/50 v/v). The spectrum was recorded with a 0.1 mT modulation
amplitude. Simulations were performed using the EasySpin package using a correlation time of τc = 15
ns. (B) Low-temperature EPR spectrum taken at 77 K in d8-THF. The spectrum was recorded using a
modulation amplitude of 0.2 mT.
EPR Spectroscopy
The 9 GHz liquid-state EPR spectrum of 1 mM 4 in 1:1 DMSO/H2O (Figure 2A) shows an EPR
spectrum typically observed for nitroxide radicals in solution. The spectrum consists of three lines
separated by the isotropic hyperfine coupling due to the interaction with a
14
N nucleus (I = 1) and an
isotropic hyperfine coupling of 1.55 mT (43.45 MHz) was measured from the spectrum. The intensity of
the high-field line is strongly attenuated due to anisotropic tumbling of the biradicals and a correlation
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time τc of 15 ns was obtained by numerical simulation of the spectrum. No further features are observed
in the spectrum indicating a negligible exchange coupling (MHz).
The 9 GHz EPR spectrum of disulfoxide dinitroxide 8 (0.4 mM) in toluene at room temperature
exhibits a triplet (aiso(14N) = 1.49 mT, g = 2.00589, Figure 3A) similar to the EPR spectrum of a
monomeric nitroxide recorded under the same conditions. Similar spectra were observed for bTbK and
tetrasulfone dinitroxide 4 (Figure 2A). The pattern of the spectrum is characteristic of a dinitroxide
having weak exchange coupling (J << aiso(14N)). However, the EPR spectrum of dinitroxide 7 exhibits a
more complex 9 line pattern in toluene (Figure 3B). This feature could be due to a higher torsional
flexibility of the molecule, which gives rise to larger exchange coupling (J ≈ aiso(14N)).45 The calculated
EPR parameters of 7 are aiso(14N) = 1.47 mT and g = 2.00586 (Figure 3B).
Figure 3. 9 GHz EPR spectra of biradicals 8 and 7. (A) Spectrum of dinitroxide disulfoxide 8 in
toluene at room temperature (J << aiso(14N)). (B) Spectrum of dinitroxide 7 in toluene at room
temperature (J ≈ aiso(14N)).
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The 9 GHz spectra of the frozen solution of biradical 4 in THF is dominated by the large Azz
component of the
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N hyperfine interaction tensor (Figure 2B, AZZ = 3.5 mT). In addition, several
spectral features indicate the presence of an electron-electron dipolar coupling. Most notable is the
splitting on the high-field side of the spectrum corresponding to the DZZ component of the dipolar
interaction tensor. A dipolar coupling of 15.1 MHz can be estimated from the spectrum. Though less
well-resolved, the observed EPR spectrum is very similar to that of bTbk, which exhibited a dipolar
coupling of 22.1 MHz.46 This may be a direct consequence of the smaller dipolar coupling between the
electrons due to the increased N-to-N distance.
Figure 4. 140 GHz EPR spectrum of biradical 4 in toluene recorded at 20 K. Top: absorption spectrum.
Bottom: pseudo-modulated spectrum using a modulation amplitude of 0.4 mT, to remove highfrequency noise the spectrum was smoothened using a binominal weighted moving average function.
Particular care was taken to not mask any spectral features. The spectrum was recorded using a threepulse echo sequence with equally spaced pulses (π/2-τ-π/2-τ-π/2) giving overlap of the Hahn echo and
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stimulated echo for additional sensitivity. The π/2 pulse lengths were 120 ns, and the delay between
pulses was 400 ns. 801 field points were acquired, with 300 shots per point, and 10 ms between shots.
At 140 GHz the solid-state EPR spectrum of biradical 4 is dominated by the large electron ganisotropy (Figure 4). With a relatively small electron-electron dipolar coupling the high-field EPR
spectrum of 4 resembles that of a monomeric nitroxide-based radical. However, the pseudo-modulated
representation reveals some additional features that can be attributed to the electron-electron dipolar
coupling.47 From this spectrum a hyperfine coupling of 95.3 MHz (AZZ) and an electron-electron dipolar
coupling of 18.1 MHz (DZZ) were measured. The origin of the difference between the measured dipolar
coupling for 4 of 18.1 MHz in toluene at 20K and 15.1 MHz in THF at 77K is currently unknown.
DNP Spectroscopy
Samples of 1a-c (10 mM) in d6-DMSO/D2O/H2O (60:34:6) with 1.0 M urea were used in DNP
experiments to compare their performance with the polarizing agent TOTAPOL. In all cases the 1H
enhancement is indirectly monitored by measuring the
13
C signal intensity of 1M
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C urea in d6-
DMSO/D2O/H2O (60/34/6 v/v/v) after a subsequent 1H-13C cross-polarization step48 with (on) and
without (off) microwave irradiation. The enhancement factor is determined from the ratio of the signal
observed with and without microwave irradiation. Note that the large urea concentration is only
necessary to observe the off-signal in a reasonable acquisition time.
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Figure 5: 140 GHz DNP enhancement profile and EPR spectrum of biradical 1. Top: 140 GHz EPR
spectrum. Bottom: 1H-detected DNP enhancement profile of biradical 1, biradical 8, bTbk, and
TOTAPOL (data for bTbk and TOTAPOL taken from ref. 7). T = 90 K, tp(π/2) = 3 µs. All enhancement
profiles are recorded under similar experimental conditions.
In our DNP experiments performed at 5 T (212 MHz 1H Larmor) the microwave frequency of the
gyrotron is fixed at 139.662 GHz. Therefore, to determine the correct position for optimum DNP
enhancement a DNP-enhancement profile is recorded by sweeping the magnetic field and measuring the
DNP enhancement for each field position. The field-dependent DNP enhancement profile for biradical 1
is shown in Figure 5 with field positions for maximum positive and negative enhancement at 4980.7 mT
(DNP(+)) and 4969.4 mT (DNP(-)), respectively. The enhancement profile observed for biradical 1 is
very similar to those recorded for 1H-DNP of other polarizing agents based on bis-nitroxides (Figure
5).16-19,49 The profile shows a slight asymmetry and only 75% of the maximum enhancement is observed
at a field position corresponding to DNP(-) as compared to DNP(+). This observation is similar to bTbk
and seems to be an intrinsic feature of rigid biradicals with a similar conformation like 1 or bTbk.18 In
contrast, TOTAPOL shows a much less pronounced asymmetry (Figure 5) that is most likely a direct
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result of the more flexible linker between the nitroxide moieties. The enhancement profile (Figure 5) is
very closely related to the high-field EPR spectrum recorded at a similar field strength (Figure 4 and top
of Figure 5). Since the dipolar coupling is small (~20-30 MHz) compared to the hyperfine coupling and
the breadth of the EPR spectrum, the shape of the spectrum is governed by the large g-anisotropy and
the 14N hyperfine interaction.
Figure 6. DNP enhancements of TOTAPOL versus 1. The enhancement in the 13C-NMR signal of urea
when biradical 1a (blue) is used as the polarizing agent is 10% greater than when TOTAPOL (red) is
used under the same conditions. The signal in the absence of DNP enhancement is show at the bottom
in black (magnified 10-times).
In Figure 6 the DNP-enhanced MAS-NMR spectra of
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C-urea are shown using TOTAPOL and
biradical 1 as polarizing agents. Due to the increased solubility of 1 both polarizing agents were studied
at a concentration of 10 mM in a 60/40 mixture of DMSO/H2O. Because of solubility limitations, this
was not possible in the case of bTbk. In particular, the water content had to be reduced which resulted in
a decreased enhancement, due to the poor glass-forming ability of the mixture.18 All three samples (1ac) gave the same signal enhancements (ε) within the experimental error, and the enhancements obtained
were 10% greater than those for TOTAPOL under similar experimental conditions. A bulk-polarization
build-up time of τB = 4 s was observed (data not shown), similar to build-up times recorded for
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TOTAPOL and bTbk.17,18 The consistency of the enhancements among 1a-c suggests that within these
three samples the oxidation states of the sulfur atoms have a minor effect on DNP performance beyond
its important effect on solubility.
Biradical 8 shows a similar DNP performance compared to biradical 1, but important differences in
it’s DNP behavior are evident. The field dependent enhancement profile (Fig. 5) exhibits a more
pronounced asymmetry between the positive and negative legs than any other biradical in this
comparison. Only ~53% of the maximum DNP(+) enhancement can be obtained at the DNP(-) position.
The maximum positive enhancement, however, is obtained at a field very similar to that of the other
biradicals. At high microwave power biradical 8 yielded ~5% higher enhancement than 1 (see Fig. 7).
The slightly higher ε is accompanied by a slower build-up of polarization; we measured
monoexponential build-up time constants of 5.5 s for biradical 8 vs. 4.0 s for biradical 1 (cf. 3.8 s for
TOTAPOL) under identical conditions. These discrepancies might be caused by differences in EPR
interactions, electronic relaxation times or the mutual orientation of the nitroxide moieties between
biradical 8 and the constituents of biradical 1 mixture. The complex interplay between these observables
and the effect on enhancement factor and their respective field dependence as well as the build-up time
constants is not yet understood. In practice, however, the benefits from a significantly shorter build-up
time constant allowing for faster recycling of NMR experiments and therefore higher sensitivity
outweigh the slightly increased DNP enhancement performance of biradical 8 over biradical 1.
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Figure 7. Microwave power dependent enhancement factors of Biradical 1 (blue), Biradical 8 (green)
and TOTAPOL (red) for comparison. All polarizing agent solutions were prepared from the same
glycerol/water mixture in order to maximize comparability. Enhancement factors were determined by
recording a full build-up curve at each power level, and dividing the pre-exponential factor (Signal
intensity at infinite time) of an exponential fit by the respective factor of a build-up curve recorded
without mw irradiation for each biradical (off-signal). All experiments were performed at ~84 K.
Conclusion
In summary, we report the synthesis of oxidized bis-thioketal-trispiro dinitroxide biradicals. When
fully oxidized to the tetrasulfone (4), the biradical has a rigid orthogonal geometry but lacks the desired
solubility. Furthermore, we showed that a biradical mixture (1) containing intermediate oxidations
states improves solubility in aqueous solvents, most likely as a result of the more polarized sulfuroxygen bonds in sulfoxides and the presence of a range of regioisomers and stereoisomers. The
mixtures show DNP enhancements similar to the previously reported biradical of similar geometry
(bTbk) and improved performance over the geometrically unconstrained TOTAPOL biradical. We also
showed that biradical 8 gives slightly higher enhancements over biradical 1, but that a shorter builduptime constant for biradical 1 gives better overall sensitivity. Future work will focus on improving the
solubility in glycerol/water solutions to broaden potential applications.
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Experimental section
Biradical mixture (1). In a flask, 0.300 g (0.62 mmol, 1.0 equiv) of 2b was dissolved in 45 mL of dry
solvent (CH2Cl2, C6H6, or CH3CN). While stirring at room temperature, 1.03 g (4.37 mmol, 7.1 equiv)
of m-chloroperbenzoic acid (73% pure by weight as determined by titration with iodine) was added in
one portion, and the reaction was stirred overnight. For the reactions in benzene and acetonitrile, the
organic solvent was removed under vacuum and the solid was redissolved in 45 mL of dichloromethane.
The organic layer was washed with saturated sodium bicarbonate (3 times) and 0.1 M HCl (3 times),
after which it was transferred to a flask and stirred under an aqueous 0.5 M NaOH solution containing
0.200 g (0.62 mmol, 1.0 equiv) of potassium ferricyanide for 10 minutes. The organic layer was washed
with brine and then dried over sodium sulfate. The solvent was removed, and the solid was redissolved
with 5.0 mL of CH2Cl2. To the solution was added 10.0 mL of hexane, which caused a precipitate to
form. After 10 minutes, the solid was isolated by filtration. Mass recovery and yield based on addition
of 6 oxygen atoms (MW = 596 g/mol): CH2Cl2, 0.170 g (47%); C6H6, 0.075 g (21%); CH3CN, 0.083 g
(23%).
Elemental Analysis for sample 1a failed for sulfur in producing the expected value: Found: C
47.89, H 7.08, N 4.67, S 21.21. Expected for C23H40N2O6.5S42•: C, 47.89; H, 6.99; N, 4.86; S, 22.24.
The nature of the impurities causing the discrepancy are not known, but the elemental analysis in
combination with the NMR, IR, MS, EPR, and DNP data suggest a mixture of the proposed biradicals.
2,2,4,4,14,14,16,16-octamethyl-7,11,18,21-tetrathia-3,15-diazatrispiro[5.2.2.512.29.26]
henicosane-
3,15-diium dichloride (2a). To a 500-mL flask were added 0.895 g (5.20 mmol, 1.0 equiv) of 2,2,6,6tetramethyl-4-piperidone monohydrate, 0.990 g (2.70 mmol, 0.52 equiv) of tetraacetyl pentaerythrithiol,
and 50 mL of concentrated hydrochloric acid. After attaching a water-cooled condenser, the reaction
mixture was heated to reflux for 3 hours. A white precipitate formed soon after heating began. Upon
cooling, the solution was filtered and washed with tetrahydrofuran to obtain 1.13 g (80% yield) of
compound 2a as a white powder. 1H NMR (500 MHz, CD3OD): δ 3.18 (s, 8H), 2.40 (s, 8H), 1.62 (s,
24H); 13C NMR (126 MHz,) 57.8, 46.7, 45.2, 35.2, 28.8, 24.0; MS (ESI) of calc for 2b (free diamine):
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C23H42N2S4 [M+H]+ 475.2304, found 475.2198. Satisfactory HRMS could not be obtained. Mp =
decomposes > 330 ˚C (conc. HCl).
2,2,4,4,14,14,16,16-octamethyl- 7λ6, 11λ6, 18λ6, 21λ6-tetrathia-3,15-diazatrispiro [5.2.2.512.29.26]
henicosan - 7,7,11,11,18,18,21,21-octone (3). To a flask were added 0.200 g (0.36 mmol, 1.0 equiv) of
compound 2a, 6.0 mL CCl4, 6.0 mL of acetonitrile, 8.0 mL of water, 0.006 g of RuCl3 (0.028 mmol, 8
mol%), and 0.706 g periodic acid (3.1 mmol, 8.5 equiv). The reaction mixture was stirred for 30
minutes at room temperature and then filtered through celite on a fritted filter. The organic solvents
were removed and sat’d sodium carbonate solution was added to reach pH = 12. The aqueous mixture
was extracted with CH2Cl2, which was subsequently dried over sodium sulfate. After removal of the
solvent, 0.090 g (46% yield) of tetrasulfone-3 was obtained. 1H NMR (500 MHz, CD3OD/CDCl3): δ
3.84 (s, 8H), 2.36 (s, 8H), 1.29 (s, 24H); 13C NMR (126 MHz, d6-DMSO/CDCl3 with 2.0 equivalents of
trifluoroacetic acid added to improve solubility, 50 ˚C): 82.5, 53.1, 50.1, 29.5, 29.0(2); HRMS (ESI):
calc’d for C23H42N2O8S4 [M + H]+ 603.1897, found 603.1890;. FT-IR: νmax(KBr)/cm-1: 3350 (br),
2919, 1450, 1388, 1373, 1343, 1314, 1167, 1149, 1129, 1019, 815, 666, 620, 579, 520.
Mp =
decomposes > 325 ˚C (methanol).
2,2,4,4,14,14,16,16-octamethyl- 7λ6 ,11λ6 ,18λ6 ,21λ6-tetrathia-3,15-dinitroxyltrispiro [5.2.2.512.29.26]
henicosan-7,7,11,11,18,18,21,21-octone (4). To a flask were added 0.078 g (0.13 mmol, 1.0 equiv) of
compound 3, 0.096 g (0.39 mmol, 3.0 equiv) of m-chloroperbenzoic acid (75% purity), 6.0 mL CH2Cl2,
and 6.0 mL of isopropyl alcohol. The solution was stirred at room temperature overnight. In a
separatory funnel, the organic layer was washed with excess sat’d sodium bicarbonate solution, with 0.1
M HCl, and brine, before being dried over sodium sulfate.
After removal of the solvent and
recrystallization from acetone, 0.058 g (70% yield) of biradical 4 was isolated as a light yellow crystal.
HRMS (ESI) calcd for C23H40N2O10S42• [M – H]- 631.1493, found 631.1504. FT-IR: νmax(KBr)/cm-1:
2935, 1456, 1388, 1373, 1362, 1345, 1314, 1234, 1150, 1131, 1018, 865, 666, 617, 589, 522; MP =
decomposes > 200 ˚C (acetone). For NMR characterization, 0.010 g of the biradical was reduced with
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H NMR (500 MHz, CD6O ): δ 3.80 (s,
8H), 2.53 (s, 8H), 1.25 (s, 24H).
1-(tert-butyldimethylsilyloxy)-2,2,6,6-tetramethylpiperidin-4-one (5).
Under inert atmosphere, 1-
hydroxy-2,2,6,6-tetramethylpiperidin-4-one (3 g, 18 mmol) was added to a mixture of imidazole (3.9 g,
57 mmol) and tert-butyldimethylchlorosilane (4.3 g, 28 mmol) in dry DMF (13 mL). The solution was
stirred 38h at room temperature and then diluted with 35 ml of hexane. The mixture was washed with
water (10 mL) and the organic phase was dried over sodium sulfate. The crude product was purified via
column chromatography (Al2O3, ether-pentane 5/95) to give 5 as a white solid (4.3 g, 84% yield). 1H
NMR (400 MHz, CDCl3): δ 0.20 (s, 6H), 0.97 (s, 9H), 1.18 (s, 12H), 2.39 (broad s, 4H); 13C NMR (100
MHz, CDCl3): δ -1.75, 19.45, 26.50; 26.97, 53.79, 63.28, 208.3. MS (ESI) calcd for C15H32NO2Si [M +
H]+, [M + Na]+ 286, 308; found 286, 308.
3,15-bis[(tert-butyldimethylsilyl)oxy]-2,2,4,4,14,14,16,16-octamethyl-7,11,18,21-tetrathia-3,15diazatrispiro[5.2.2.512.29.26]henicosane (6): A mixture of 5 (1.30 mmol, 0370 g), pentaerythrityl
tetrathiol26 (0.65 mmol, 0.130 g) and boron trifluoride etherate (3.25 mmol, 0.80 mL) in dry CH2Cl2 (6
mL) was stirred for 5 days at room temperature and under inert atmosphere. The mixture was quenched
by adding a solution of sodium hydroxide 1 M (10 mL). The aqueous phase was extracted with
dichloromethane (15 mL). The organic layers were collected, washed with a solution of sodium
hydroxide 1 M (10 mL), dried over Na2SO4 and the solvent was distilled under reduced pressure. The
product was purified by crystallization from pentane (0.358 g, 75%).
1
H NMR (400 MHz, CDCl3): δ
0.14 (s, 12H), 0.95 (s, 18H), 1.26 (s, 24H), 2.18 (s, 8H), 2.32 (s, 8H); 13C NMR (100 MHz, CDCl3): δ 1.90, 19.52; 22.79; 26.86; 27.01; 35.58; 47.52; 49.66; 60.50. MS (ESI) calc’d for C35H70N2O2S4Si2
[M+Na]+ 758, found 758.
2,2,4,4,14,14,16,16-octamethyl-7,11,18,21-tetrathia-3,15-dinitroxyltrispiro[5.2.2.512.29.26]
henicosane (7). To a solution of 6 (0.20 mmol, 150 mg) in CH3CN (2 mL) was added HF (48% in
water, 5 drops). The solution was stirred for 2 hours at room temperature and then aqueous saturated
NaHCO3 solution (10 mL) was added. Solid sodium chloride was added and the aqueous phase was
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extracted with CH2Cl2 (2 X 20 mL). The organic phase was dried over sodium sulfate and the solvent
was removed under reduced pressure. The crude light yellow oil was dissolved in MeOH (3 mL) and
stirred for 2 days in the presence of MnO2 (50 mg). The mixture was filtrated and the residual oil was
purified by SiO2 chromatography column (DCM / EtOH, 9 : 1) to afford the dinitroxide 7 as orange
crystals (36 mg, 38 % yield). Pure samples were also obtained by semi preparative HPLC (purosphere
RP-18 column (250 mm x 10 mm; 10 µm; Merck) using a gradient with a flow rate of 3 mL.min-1.
Gradient: solvent A (0.1% TFA in H2O, pH=2.6), solvent B (CH3CN): 0-25 min, 10-40% B; 25-35 min,
40-60% B; 35-40 min, 60% B. 1H NMR (400 MHz, CDCl3, phenylhydrazine): δ 1.34 (s, 24H), 2.24 (s,
8H), 2.97 (s, 8H). MS (ESI) calc’d for C23H40N2O2S4 [M+H]+ ,[M+Na]+ 507, 527; found 507, 527.
2,2,4,4,14,14,16,16-octamethyl- 7λ6 ,11λ6 ,18λ6 ,21λ6-tetrathia-3,15-dinitroxyltrispiro [5.2.2.512.29.26]
henicosan-7,18-dione (8). To a solution of 6 (150 mg, 0.20 mmol) in dry ether was added dropwise a
solution of m-CPBA (2.2 equivalents, 0.56 M in ether) at 0 °C. The mixture was stirred for 1 hour at
0°C. A white precipitate (120 mg) was collected by filtration and dissolved in acetonitrile (1 mL). HF
(48% in water, 2 drops) was added to the solution. The mixture was stirred for 14 h and then aqueous
saturated NaHCO3 solution (10 mL) was added. Solid sodium chloride was added and the aqueous phase
was extracted with CHCl3 (2 X 20 mL). The organic phase was dried over sodium sulfate and the
solvent was removed under reduced pressure. The crude light yellow oil was dissolved in MeOH (3 mL)
and stirred for 1 day in the presence of MnO2 (50 mg). The residual oil was purified by SiO2 column
chromatography (CH2Cl2/EtOH, 95:5) to afford the dinitroxide disulfoxide 8 as an orange solid (56 mg,
50 % yield). Pure samples were also obtained by semi preparative HPLC (purosphere RP-18 column
(250 mm x 10 mm; 10 µm; Merck) using a gradient with a flow rate of 3 mL.min-1. Gradient: solvent A
(0.1% TFA in H2O, pH=2.6), solvent B (CH3CN): 0-25 min, 10-40% B; 25-35 min, 40-60% B; 35-40
min, 60% B. HRMS (ESI):) calc’d for C23H40N2O4S42• [M + H]+ 537.1944, found 537.1930. FT-IR
νmax/cm-1 (ATR) 3693, 2979, 2245, 1602, 1238, 1044.
EPR Spectroscopy
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EPR experiments were performed on a custom-designed high-field EPR spectrometer operating at a
microwave frequency of 139.504 GHz.50,51 The sample, with a volume of approximately 250 nL, was
placed in a Suprasil quartz tube with an outer diameter of 0.55 mm. EPR spectra were recorded by using
a two-pulse echo sequence (π/2–τ–π–τ–echo) by integrating the echo intensity while sweeping the
magnetic field. Detailed experimental conditions are given in the figure legend. For accurate field
measurements, the spectrometer was equipped with a field/frequency lock system.52 EPR measurements
for biradical 7 and 8 were performed on an X-band CW-EPR (9.8 GHz, 0.34 T) spectrometer at room
(RT). Spectral simulations have been carried out using the EasySpin package.53
DNP Spectroscopy
DNP experiments were performed on a custom designed 211 MHz DNP NMR spectrometer using a
triple-resonance low-temperature 2.5 mm MAS probe (e-, 1H,
13
C) with a commercial stator. The
spectrometer operates at a magnetic field of 5 T, corresponding to an electron Larmor frequency of 140
GHz. High-power microwave radiation (>10 W) is generated by a gyrotron, operating at a frequency of
139.662 GHz.
9,51,54
The NMR magnet is equipped with a superconducting sweep coil that allows field
sweeps over ±750 G. For accurate field measurements the spectrometer is equipped with a
field/frequency lock system.52 All experiments were performed at 90 K at a spinning frequency ωr/2π
π =5
kHz and 100 kHz TPPM 1H decoupling.55 The 1H and
13
C field strengths used for cross-polarization
were typically 50 kHz.
Acknowledgement. This research was supported by the National Institutes of Health (NIH) through
grants EB002804, EB002026 and GM095843 and by the European Commission in the Design Study
project Bio-DNP. T.M. acknowledges receipt of a postdoctoral fellowship from the Deutsche
Forschungsgemeinschaft (DFG). We thank Dr. Peter Mueller for collecting and solving X-ray crystal
structures and Alexander Barnes, Galia Debelouchina, and Hakim Karoui for stimulating discussion.
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The Journal of Organic Chemistry
Supporting Information Available: FT-IR, ESI-MS, and NMR spectra. X-ray crystallographic details
of compounds. This material is available free of charge via the Internet at http://pubs.acs.org.
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ACS Paragon Plus Environment
27
Supporting Information for “Rigid Orthogonal bis-TEMPO Biradicals with Improved Solubility for Dynamic Nuclear Polarization”
Eric L. Dane1, Björn Corzilius1, 2 , Egon Rizzato3, Pierre Stocker4, Thorsten Maly1, 2, Albert A.
Smith1, 2, Robert G. Griffin1, 2,*, Olivier Ouari3,*, Paul Tordo3, and Timothy M. Swager1*
1
3
Department of Chemistry and 2Francis Bitter Magnet Laboratory, Massachusetts Institute of
Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 USA
SREP LCP UMR 6264, Aix Marseille Universities, Faculté de Saint Jérôme, 13013 Marseille,
France
* tswager@mit.edu, rgg@mit.edu, olivier.ouari@univ-provence.fr
Table of Contents
Figure S1 - MM Modeling
Figure S2 - IR spectra
Figure S3 - ESI-MS 1a
Figure S4 - ESI-MS 1b
Figure S5 - ESI-MS 1c
Figure S6 - ESI-MS 7, 8
1
H-NMR 1a,b,c
1
H-NMR 2a
13
C-NMR 2a
1
H-NMR 3
13
C-NMR 3
1
H-NMR 4’
1
H,13C-NMR 5
1
H,13C-NMR 6
Solid State X-band EPR of 7 and 8
XRCS - ORTEP 3,4, and 7 Figure S7 - CSD analysis of C-S-C bond angles
XYZ coordinates of MM structures S1-S21
pg. S2
pg. S3
pg. S4
pg. S5
pg. S6
pg. S7
pg. S8
pg. S9
pg. S10
pg. S11
pg. S12
pg. S13
pg. S14
pg. S15
pg. S16
pg. S17-19
pg. S20-21
pg. S22-52
S1
Structure
General Structure (S2)
O
N O
O
SO
O
S1 (bTbk calc.)
O N
S
S
S
N O
S
O
O N
O N
S
S
O S
S
S
S
S
O
O N
N O
S
O N
O
O S4
S3,S4 (Biradical 8 calc.)
O N
S
S
S
O
O N
N O
S
S
S
N O
S
O N
S6
O N
S
S
S
S
S7
O N
S
S
O S
S
O S
O
S
O S
O N
90.4
13.0
10.7
2
(Biradical 7 calc.)
90.9
14.4
12.1
Biradical 7
(X-ray CS)
98.9
14.7
12.1
3
90.0
14.5
12.4
4
94.1
14.6
12.4
5
92.4
14.6
12.3
6
91.0
14.6
12.1
7
95.4
14.4
11.9
8
91.0
14.8
12.1
9
91.5
14.5
12.0
10
93.3
14.7
12.4
11
91.2
14.8
12.1
12
90.5
14.7
12.0
13
92.2
14.7
12.4
14
95.5
14.5
12.3
O
S O
S
S
S
O O
15
95.2
14.7
12.3
16
91.5
14.6
11.9
17
(Biradical 4 calc.)
92.5
14.9
12.2
Biradical 4
(X-ray CS)
93.6
14.6
12.2
18
92.0
14.6
11.9
19
91.0
14.6
11.9
20
93.2
14.9
12.1
21
95.3
14.7
12.1
Biradical 8
calc.
N O
O
N O
N O
S
O O
O
S
S
S
N O
S
O O
O
S
S
S
O
O N
O
N O
O
N O
S
O
S20
N O
O
O
S
O O
S
S
O O
O
O
S
S11
N O
S19
O
S
S
O O
N O
S
S10
O N
O N
O
S
bTbk
(X-ray CS)
O
S15
O
S
S9
O N
N O
O
S
S
O S
11.1
S18
O
S
S8
O N
O N
O
O
O
S
O
N O
N O
S
O
O
S17 (Biradical 4 calc.)
O
O
S
S16
O
12.6
O
S14
SO
O
91.5
O
S
S
S
O
S5
S
S
S
S
O N
N O
O
S13
O
O
S
S
O
S
O
O
O
S12
S
S
O
S3
O N
N O
N O
S
O
S2 (Biradical 7 calc.)
O
S
S
O N
N to N
Distance
(Ǻ)
1
(bTbk calc.)
plane 2
O
O
O to O
distance
(Ǻ)
dihedral
angle °
plane 1
O N
Dihedral
Angle (˚)
S
S
S
O O
O
S
S21
O
N O
Figure S1.
Molecular mechanics modeling (MMFF94) of the effect of oxidation state on biradical geometry.
The table reports the measured values from the calculated structures and the available values from
XRCS data. The nitrogen-oxygen bond was modeled as a single bond. Modeling was performed
using MacSPARTAN ‘06.
S2
2600
3000
2200
O
S
O
O
S
S
O
O
S
O
O
O
HN
3
1800
1000
1400
600
NH
SO2
SO2
O N
O
O
S
O
O
S
S
O
O
S
O
O
4
N O
.
NO
1362
.
NO
1235
SO2
1a
Transmittance
SO2
.
NO
1362 SO2 NO.
SO2 SO
1235
1b
.
NO
1362
SO2
.
NO
1235
SO2
1c
X
O N
X=
3000
X
X
S
N O
X
or
O
S
2600
or
O
S
O
SO
1a
1b
1c
2200
Figure S2.
FT-IR of compounds 3, 4, 1a, 1b, and 1c.
.
NO
1362 SO2
reaction
solvent
CH 2 Cl2
C 6 H6
CH 3CN
.
Nitroxide (NO )
Sulfone (SO2)
Sulfoxide (SO)
1800
wavenumber (cm-1)
1400
.
NO
1235
SO
SO2
1000
600
S3
species (Mx ):
O
N
a
example
structure:
(O)S
S(O) b
(O)S
S(O)d
c
M2
M3
M4
M5
M6
O
N
O
N
O
N
O
N
O
N
(a + b + c + d) = x
O
S
S
S O
N
O
molecular
weight (amu):
err or = ± 1 a mu
O
S
S
S
S O
O
O
S
S
S
S
O
O
O
O
S
S
S
S
O
O
O
O
S
S
O
S
O
S
O
O
O
N
O
N
O
N
O
N
O
N
O
[M 2 + 2H]+ = 538
[M 2 + Na]+ = 559
[M3 + 2H] + = 554
[M3 + Na]+ = 575
[M4 + 2H]+ = 570
[M4 + Na]+ = 591
[M5 + 2H]+ = 586
[M5 + Na]+ = 607
[M6 + 2H]+ = 602
[M6 + Na]+ = 623
1a
a, b, c, d = 0, 1, or 2
a+ b + c + d = 4± 2
O
S
[M4 + Na]+ = 591
[M5 + Na]+ = 607
[M3 + Na]+ = 575
592
[M4 + 2H]+ = 570
593
[M3 + 2H] + = 554
[M 2 + 2H]+ = 538
520
525
530
535
540
[M6 + Na]+ = 623
545
550
555
560
565
570
575
580 585
m/z, amu
590
595
600
605
610
615
620
625
630
635
640
Figure S3.
Electrospray Ionization (ESI) MS of biradical mixture 1a. Sample was loaded in a methanol solution with 0.1 mM sodium perchlorate and detected in positive ion mode.
S4
S4
species (Mx ):
a
example
structure:
(O)S
S(O) b
(O)S
S(O)d
c
M2
M3
M4
M5
M6
O
N
O
N
O
N
O
N
O
N
(a + b + c + d) = x
O
N
O
N
O
molecular
weight (amu):
err or = ± 1 a mu
S
S
S O
O
S
S
S
S O
O
O
O
S
S
S
S
O
O
O
O
S
S
S
S
O
O
O
O
S
S
O
S
O
S
O
O
O
N
O
N
O
N
O
N
O
N
O
[M 2 + 2H]+ = 538
[M 2 + Na]+ = 559
[M3 + 2H] + = 554
[M3 + Na]+ = 575
[M4 + 2H]+ = 570
[M4 + Na]+ = 591
[M5 + 2H]+ = 586
[M5 + Na]+ = 607
[M6 + 2H]+ = 602
[M6 + Na]+ = 623
1b
a, b, c, d = 0, 1, or 2
a+ b + c + d = 3 - 6
S
[M5 + Na]+ = 607
[M4 + Na]+ = 591
[M6 + Na]+ = 623
[M3 + Na]+ = 575
[M4 + 2H]+ = 570 [M5 + 2H]+ = 586
[M3 + 2H] + = 554
520
525
530
535
540
545
550
555
560
565
570
575 580 585
m/z, amu
590
595
600
605
610
615
620
625
630
635
640
Figure S4.
Electrospray Ionization (ESI) MS of biradical mixture 1b. Sample was loaded in a methanol solution with 0.1 mM sodium perchlorate and detected in positive ion mode.
S5
S5
species (Mx ):
a
example
structure:
(O)S
S(O) b
(O)S
S(O)d
c
M2
M3
M4
M5
M6
O
N
O
N
O
N
O
N
O
N
(a + b + c + d) = x
O
N
O
N
O
molecular
weight (amu):
err or = ± 1 a mu
S
S
S O
O
S
S
S
S O
O
O
O
S
S
S
S
O
O
O
O
S
S
S
S
O
O
O
O
S
S
O
S
O
S
O
O
O
N
O
N
O
N
O
N
O
N
O
[M 2 + 2H]+ = 538
[M 2 + Na]+ = 559
[M3 + 2H] + = 554
[M3 + Na]+ = 575
[M4 + 2H]+ = 570
[M4 + Na]+ = 591
[M5 + 2H]+ = 586
[M5 + Na]+ = 607
[M6 + 2H]+ = 602
[M6 + Na]+ = 623
1b
a, b, c, d = 0, 1, or 2
a+ b + c + d = 3 - 6
S
[M5 + Na]+ = 607
[M4 + Na]+ = 591
[M6 + Na]+ = 623
[M3 + Na]+ = 575
[M4 + 2H]+ = 570 [M5 + 2H]+ = 586
[M3 + 2H] + = 554
520
525
530
535
540
545
550
555
560
565
570
575 580 585
m/z amu
590
595
600
605
610
615
620
625
630
635
640
Figure S5.
Electrospray Ionization (ESI) MS of biradical mixture 1c. Sample was loaded in a methanol solution with 0.1 mM sodium perchlorate and detected in positive ion mode.
S6
Mass Spectrum analysis:
ESI-MS spectrum of biradical 7.
Figure S6.
HR Mass spectrum (ESI, positive electrospray mode) of biradical 8. The targeted ions are
detected at m/z 537.1930 and m/z 554.2204 and the peaks used for internal calibration are
observed at m/z 500.3792 and m/z 558.4211.
S7
Biradical 1 1H-NMR
H 20
CHD2OD
CD3OD, 500 MHz
Biradical 1c (reduced)
Biradical 1b (reduced)
Biradical 1a (reduced)
Biradical 1*
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0 ppm
* Spectra of unreduced 1a, 1b, and 1c are identical
O
N
HO
N
S
or
or
X
X
X=
X
X
O
N
O
1
1a
1b
1c
X
O
S
Zn-powder
or
d 4 -MeOH
S
S
X
O
S
X=
X
X
or
O
O
N
OH
S
O
1 (reduced)
reaction
solvent
CH2 Cl2
C6 H6
CH 3CN
S7
S8
S9
S8
10.0
9.5
Cl H
N
H
9.0
8.5
8.0
S
S
2a
S
S
7.5
N
7.0
H Cl
H
6.5
6.0
5.5
5.0 4.5
ppm
4.0
3.5
3.0
2.5
2.0
1.5
3.18
7.64
CD3OD, 500 MHz
2.40
8.00
Compound 2a 1H-NMR
1.62
25.28
1.0
0.5
0.0
S10
S9
200
190
180
Cl H
N
H
160
S
S
2a
S
S
170
CD3OD, 126 MHz
Compound 2a 13C-NMR
150
H Cl
H
140
N
130
120
110
100 90
ppm
80
70
57.8
60
46.7
45.2
50
40
28.8
30
24.0
35.2 (br)
20
10
0
-10
HN
8.5
7.5
CHCl3
8.0
7.0
6.5
6.0
5.5 5.0
ppm
CH2Cl2
9.0
NH
H 2O
9.5
S
O
O
S
O
O
3
O
O
S
O
S
4.5
3.84
4.0
6.50
O
3.5
3.0
2.36
2.5
8.05
CD3OD/CDCl3, 500 MHz
2.0
1.29
1.5
25.60
Compound 3 1H-NMR
CHD2OD
S11
S10
1.0
0.5
0.0
HN
100
95
90
NH
85
80
O
75
2 F 3C
d-chloroform
110
105
S
O
O
S
O
O
3
O
O
S
O
S
O
82.5
d6-DMSO/d-chloroform, 126 MHz, T = 50 ˚C
Compound 3 13C-NMR
70
OH
65
60
53.1
50.1
55
50
f1 (ppm)
45
40
d6-dimethylsulfoxide
S12
S11
35
30
31.4
29.5
29.0
25
20
15
10
5
0
-5
O N
9.5
9.0
S
O
O
S
O
O
4
O
O
S
O
S
O
8.5
N O
8.0
d 6 -acetone
HO N
7.5
7.0
O
S
S
O
O
O
6.5
phenylhydrazine and
oxidized products
phenylhydrazine
(excess)
6.0
4'
N OH
5.5 5.0
ppm
S
O
O
O
O
S
4.5
3.5
3.0
2.5
2.0
1.5
3.80
6.94
4.0
2.53
8.00
C2D6O, 500 MHz
1.25
25.84
Compound 4’ (reduced) 1H-NMR
S13
S12
1.0
0.5
Silyl tempone
0.99
Compound 5 1HNMR 400 MHz
1.20
1.0
O
0.9
0.22
0.8
0.7
N
0.6
OTBDMS
5
0.5
0.4
0.3
0.2
7.25
0.1
0.0
4.10
8.0
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
12.12
2.0
1.0
0.5
0.0
26.77
Compound 5 13CNMR 100 MHz
1.5
6.00
1.0
0.9
53.59
0.8
-1.95
0.7
0.6
0.5
0.4
63.08
77.00
Chloroform-d
208.17
0.2
19.25
0.3
0.1
0.0
200
150
100
50
0
S14
Chloroform-d
77.84
77.42
77.00
Compound 6 1HNMR 400 MHz
0.8
27.35
0.7
0.6
0.4
-1.57
60.83
0.5
35.81
0.2
24.30
49.98
47.86
19.85
0.3
0.1
0.0
150
140
130
120
bTbKS4OtBS
110
100
90
80
TBDMSO N
70
60
S
S
S
S
50
40
30
20
10
0
-10
N OTBDMS
6
0.13
0.95
Compound 6 13CNMR 100 MHz
0.7
0.6
0.5
0.4
0.3
-0.01
2.93
5.29
7.25
1.24
1.22
Chloroform-d
0.2
0.1
0.0
6.48
8.0
7.5
bTbKS4OtBS
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
7.52
2.5
2.0
23.42
1.5
1.0
12.00
0.5
0.0
S15
X-band EPR spectrum of 7 at 108 K in ethanol.
X-band EPR spectrum of 8 at 103 K in toluene.
S16
Compound 3
S17
Biradical 4
S18
Biradical 7
S19
?
S(O)n
S
n = 0,1, or 2
CSD code
AFISIR
C-S-C
angle (°)
102.441
ASIBOT
BANPUB
BANPUB
104.174
102.21
102.326
BIXKOJ
BIXLIE
C-S -C
angle (°)
104.262
CSD code
SINROX
C-S -C
angle (°)
102.481
KAMLOZ
KASHUH
104.042
102.229
SINROX
SOTHAK
101.457
102.861
102.923
101.643
KAXSIM
KIZQAL
KIZQAL
102.082
103.162
102.72
SPUNON
TACKAJ
TEGSEE
99.646
102.022
101.068
CARVOG
CARVOG
CIFBIC
CIGROZ
103.493
102.311
102.232
102.507
KOKRUX
KOMCIY
KOMCOE
KOMCOE
100.425
100.076
101.748
102.392
TEGSII
TEGSOO
TELSOS
UMACUG
102.428
102.224
100.415
99.786
CILQUK
COCHAD
COVJOM
103.065
104.903
101.347
KOMCOE
KOMCOE
101.154
101.539
UMACUG
VEDSUS
100.315
104.384
COYXUJ
CUPWOZ
103.083
103.883
KOMCUK
KOMCUK
KOMDAR
100.437
100.494
99.541
CUPWUF
CUQPIN
CURCOH
DAKYAQ
100.075
102.214
102.397
101.93
KOMDAR01
KOMDAR01
KOMDEV
KOMDIZ
100.249
99.531
101.001
99.281
VIYBUA
VIYBUA
VIYBUA
VIYBUA
100.116
100.049
100.333
99.814
VUJSUO
WAGZAG
WAGZEK
105.36
104.48
100.906
DAPVOF
DIKKAJ
FALKOT
101.688
102.062
102.477
KUPNEO
KUPNIS
102.067
102.217
WAGZEK
WAGZEK
102.687
102.784
FALKOT
FALKUZ
101.629
100.102
KURXEA
KURXEA
KUYDEN
101.712
102.287
100.522
FAMZUP
FAZSOO
FAZTIJ
FAZVAD
100.598
104.932
102.318
104.993
KUYDOX
101.26
WAGZEK
WIGQUZ
XAKYOX
XAKYOX
101.278
100.967
100.031
100.699
KUYDUD
MAWQEH
NAXXIU
100.728
102.465
102.636
YEHYAM
YEHYEQ
YEMDAW
101.88
101.127
100.752
FAZXUZ
FAZXUZ
100.505
102.649
NIPGUP
PAKZAC
102.521
100.602
YITMIX
YITMIX
102.575
102.443
FOBCOP
FOFLOC
GIBJIK
101.767
101.981
101.117
GIBJIK
HIBLEJ
INAQOD
INAQOD
101.043
101.544
100.53
101.737
PAMHIU
PAMHOA
PBSPUD
PBSPUD
103.168
102.958
101.272
99.796
YITMOD
YITMOD
ZELQIQ
ZEMSIT
97.315
101.54
103.081
101.842
PIWVOG
RICBEK
ROLJOR
100.096
102.044
101.734
ZEMSIT
ZEMSIT
ZEMSIT
101.743
99.424
100.352
IPIYOV
IQOKEE
101.745
100.238
SEDVAZ
SEYXEZ
100.773
102.79
POBQIH
101.621
JUCTUW
99.5
CSD code
KAMLIT
SINRIR
103.2
SINRIR
102.868
Avg.
Std. Dev.
101.72
1.39
Figure S7. Analysis of carbon-sulfur-carbon bond angles in X-ray crystal structures from
the Cambridge Structural Database (continued on next page).
S20
?
S(O)n
S
O
n = 0,1, or 2
CSD code
C-SO-C
angle (°)
ASEXEB
100.421
ASEXEB
101.471
ASIDAH
100.849
ASIDAH
100.468
BATVUO
100.457
BATWID
100.599
CDPTDX
99.427
CDPTDX
100.495
MEKBUA
100.297
MEKCAH
98.574
MEKCAH
98.793
MEKCAH01
98.921
MEKCAH01
98.21
MEKCEL
97.662
NACHII
100.984
NACHOO
98.473
NACHUU
99.505
NACJEG
101.1
NACJIK
100.85
NACJOQ
102.048
NACJUW
99.537
NADFUT
98.681
QAYMUZ
100.554
QAYMUZ
101.099
QEYYEY
102.13
QEYYIC
104.045
QEYYOI
105.416
RULDAD
99.882
RULDAD
101.062
SAWZEV
101.669
SUPYUX
99.258
SURKAR
100.615
SURKAR
99.174
VIDSUW
103.263
Avg.
100.47
Std. Dev.
1.65
?
S(O)n
S
O
O
n = 0,1, or 2
CSD code
BUPROT
BUPROT
CUYPUH
CUYPUH
ESEXUV
ESEXUV
GECYIX
GECYIX
JAVXAG
JAVXAG
JUBKEW
LINSAC
LINSAC
SURJIY
YOFPAK
YOFPAK
Avg.
Std. Dev.
C-SO 2-C
angle (°)
103.331
104.965
103.903
105.369
100.875
99.903
104.868
104.918
103.564
103.617
102.72
99.545
101.299
100.678
101.169
100.802
102.5954
1.97
Figure S7 (con’t). Analysis of carbon-sulfur-carbon bond angles in X-ray crystal structures
from the Cambridge Structural Database.
S21
XYZ coordinates of MM minimized structures:
Structure 1 (S1)
H
-0.087646
C
-0.111694
C
-0.029698
C
-1.632942
O
-1.314716
O
-1.401858
C
0.163777
H
0.742239
H
0.642973
H
0.046675
C
1.579177
H
2.326136
H
1.772938
C
-0.801578
H
-1.836463
H
-0.791177
O
-0.466678
O
1.815061
C
0.871946
C
1.047684
H
0.875752
H
0.234713
C
1.073007
H
0.254496
H
0.936778
C
2.400032
C
2.428533
C
3.568913
H
4.502661
H
3.325615
H
3.787966
C
2.281416
H
3.227813
H
1.546560
H
1.950967
C
3.526135
H
4.451238
H
3.778423
H
3.249275
C
2.228996
H
3.172104
H
1.872508
H
1.505142
N
2.816120
O
3.666941
C
-3.146217
H
-3.417343
H
-3.670197
C
-0.953211
-2.347420
-2.170603
-0.537574
-2.325506
-1.005997
-2.545735
-0.703504
-1.079316
-2.831118
0.511889
-0.308558
-0.841207
-0.573930
0.208825
0.073956
-0.003947
1.578594
1.090053
1.931551
3.344415
3.317786
3.972392
2.032908
2.648251
1.052408
4.016941
2.611283
1.584578
1.993973
0.690355
1.260327
3.071807
3.440455
3.880370
2.242852
3.511505
4.080808
2.461917
3.621127
5.534735
6.080300
5.733306
5.971381
3.806629
4.561718
-2.508248
-3.490465
-1.780834
-3.392373
-2.081686
-1.000441
0.829180
0.852314
1.252393
-0.535577
-0.683605
1.388465
-0.557968
1.133426
-1.104052
-0.504666
-2.149864
-1.448212
-1.115742
-2.523482
-1.238956
-0.928048
-1.567961
-0.997192
0.088776
-1.393188
-3.082928
-3.485876
-3.555673
-1.271778
-3.531328
-3.458524
-3.863572
-4.043743
-2.438792
-4.998891
-5.412572
-5.094744
-5.635780
-0.357348
-0.511669
-0.523817
0.697465
-1.037052
-1.162208
-0.019464
-1.735938
-2.700972
-3.160279
1.022269
0.605392
0.385156
1.713709
S22
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
0.137519
-1.209563
-3.679569
-1.316415
-3.805913
-4.287104
-4.418520
-2.843396
-5.082230
-5.038864
-5.750970
-5.553406
-0.947925
0.111448
-1.538227
-1.119107
-0.556254
-0.821902
0.526019
-0.760699
-2.792762
-3.261449
-3.326515
-4.375338
-2.389661
-3.356596
-0.937179
-0.885473
-0.348305
-0.430684
-3.037099
-4.106373
-2.558400
-2.944271
-4.729494
-4.957045
-5.537995
-4.762308
-2.267476
-1.255588
-2.380391
-2.323717
-3.135346
-3.427807
1.615134
1.290826
2.456494
3.210704
2.940649
3.925310
2.248409
3.041455
2.493680
2.253170
1.768677
3.479647
3.816482
3.649320
3.368325
4.899214
3.983182
3.669150
3.851937
5.059576
3.414145
4.509560
Structure 2 (S2)
H
-0.026016
C
-0.227867
C
-0.121227
C
-2.144208
S
-1.821169
S
-1.938776
C
0.081220
H
0.543671
H
0.441104
H
0.154385
C
1.574647
H
2.194511
H
1.753620
C
-0.786555
H
-1.852779
H
-0.639371
S
-0.519532
S
2.273210
C
1.240128
C
1.549837
H
1.468863
H
0.746935
C
1.397728
H
0.587909
H
1.214953
C
2.882033
C
2.724487
-2.130300
-2.002654
-0.404753
-2.401878
-0.674671
-2.566672
-0.538119
-1.091724
-2.701550
0.595253
-0.306728
-1.027723
-0.507347
0.437060
0.269062
0.263664
2.208764
1.335265
2.442538
3.918784
4.092119
4.531101
2.281961
2.861465
1.245986
4.517610
2.761853
-2.049983
-0.979356
0.960936
1.099162
1.573981
-0.726009
-0.568831
1.496763
-0.464382
1.308768
-0.928044
-0.380972
-1.990549
-1.401845
-1.224201
-2.473743
-1.067861
-0.545967
-1.561301
-1.218209
-0.134229
-1.661481
-3.081153
-3.552819
-3.392357
-1.720945
-3.714660
S23
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
3.866249
4.739905
3.554134
4.221591
2.461083
3.372460
1.726117
2.075637
4.091336
4.972182
4.395678
3.882615
2.720842
3.646557
2.447329
1.940643
3.182127
4.001485
-3.628933
-3.833739
-4.291695
-1.293776
-0.222221
-1.460792
-4.086478
-1.582114
-4.398905
-4.890636
-5.076977
-3.509977
-5.384380
-5.206852
-6.151866
-5.809248
-1.019463
0.048682
-1.533523
-1.125593
-0.912505
-1.351484
0.156902
-1.000438
-3.059304
-3.424395
1.742558
2.046293
0.758126
1.618842
2.989602
3.271703
3.786968
2.076864
4.185836
4.770953
3.139256
4.421277
6.057997
6.567201
6.432003
6.373667
4.067412
4.719174
-2.749813
-3.704880
-2.020901
-3.451492
-3.253131
-4.414306
-2.932503
-3.679021
-1.616829
-1.802859
-0.992840
-1.026101
-3.777690
-4.779562
-3.294695
-3.909495
-5.072939
-5.137312
-5.873563
-5.289941
-2.643235
-1.647447
-2.557321
-2.929167
-3.684883
-4.192174
-3.585887
-4.176293
-3.952816
-2.561692
-5.223381
-5.764358
-5.388131
-5.692869
-0.834153
-1.127656
-0.890124
0.215592
-1.739836
-2.034247
-0.746177
-2.443284
-3.122628
-3.762135
1.359515
0.847721
0.868513
1.830256
1.702447
1.321110
2.823824
3.333082
3.552306
4.515652
2.959207
3.780670
2.801976
2.392168
2.185755
3.804487
3.705032
3.466280
3.159264
4.774840
4.248663
4.168541
4.024864
5.304444
3.621512
4.677233
Structure 3 (S3)
H
0.050056
C
-0.166409
C
-0.104442
C
-2.098149
S
-1.868025
C
0.103839
-2.215238
-2.065284
-0.425463
-2.405797
-2.655640
-0.582466
-2.039896
-0.975107
0.927593
1.094979
-0.721283
-0.595102
S24
H
H
H
C
H
H
C
H
H
S
C
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
0.543069
0.509474
0.171064
1.592122
2.225667
1.779243
-0.775335
-1.839611
-0.601225
-0.559324
1.217548
1.502549
1.337615
0.737606
1.441881
0.595533
1.352782
2.884457
2.743668
3.652762
4.547096
3.120535
3.993565
2.389779
3.281516
1.709841
1.892537
3.844810
4.792516
4.098040
3.403079
2.711852
3.668747
2.283622
2.044374
3.515808
4.690708
-3.580511
-3.756653
-4.245910
-1.228130
-0.167808
-1.280882
-4.056637
-1.594615
-4.814897
-5.230972
-5.658768
-4.192675
-5.040537
-4.584651
-5.917984
-1.110439
-2.736803
0.578993
-0.332260
-1.042004
-0.515308
0.350069
0.155687
0.163284
2.129536
2.381117
3.868356
4.065160
4.470231
2.183573
2.657142
1.126509
4.440836
2.763460
1.616633
1.992888
0.981618
0.969513
3.628390
4.074937
4.446472
3.026584
4.505451
4.992194
3.525161
5.090083
5.886521
6.329346
6.527946
5.938670
3.638127
3.869737
-2.769201
-3.768640
-2.101117
-3.391865
-3.123897
-4.364339
-2.814604
-3.646369
-1.528258
-1.593700
-1.355922
-0.632520
-3.990553
-4.953904
-3.868934
1.484358
-0.433114
1.263593
-0.954731
-0.407997
-2.017913
-1.464205
-1.303015
-2.529927
-1.152473
-1.594745
-1.269852
-0.200036
-1.785853
-3.103542
-3.624525
-3.378129
-1.675379
-3.730015
-4.223123
-4.734568
-4.941641
-3.411452
-4.958515
-5.414656
-4.699014
-5.728511
-0.469293
-0.731190
-0.062951
0.346534
-2.191133
-2.492991
-1.411744
-3.057217
-2.777410
-3.043792
1.360720
0.932033
0.793822
1.893073
1.823729
1.379640
2.834731
3.384504
3.223884
4.236932
2.545152
3.198363
3.022098
2.772197
2.375913
S25
H
C
H
H
H
C
H
H
H
N
O
S
O
S
O
-5.400173
-1.709664
-0.754361
-2.458106
-1.990732
-0.477008
-0.347800
0.486364
-0.670721
-2.909458
-3.130301
2.251405
3.641400
-1.811224
-1.784830
-4.061302
-5.164276
-5.665876
-5.631663
-5.383713
-3.109865
-2.027861
-3.569846
-3.336686
-3.027494
-2.881818
1.307250
1.383688
-0.647138
-0.567100
4.055791
3.640651
3.445423
2.992353
4.677722
4.305340
4.226378
4.054097
5.360800
3.781358
4.979293
-0.535386
-1.085194
1.509337
3.004227
Structure 4 (S4)
H
-0.011973
C
-0.211919
C
-0.117047
C
-2.117525
S
-1.914511
C
0.090189
H
0.529023
H
0.462918
H
0.141985
C
1.575392
H
2.199862
H
1.721099
C
-0.764670
H
-1.832914
H
-0.568463
S
-0.539722
C
1.245517
C
1.504734
H
1.418313
H
0.685522
C
1.434466
H
0.591363
H
1.336331
C
2.814552
C
2.729676
C
3.928691
H
4.792665
H
3.681850
H
4.270611
C
2.451571
H
3.344866
H
1.672234
H
2.117783
C
4.037919
H
4.903604
-2.307816
-2.133134
-0.448207
-2.409146
-2.705250
-0.646288
-1.116845
-2.803295
0.564679
-0.442150
-1.165068
-0.653035
0.282076
0.092150
0.096865
2.051121
2.317307
3.775781
3.855319
4.397387
2.268338
2.814525
1.239296
4.464670
2.884913
1.925829
2.338325
0.967880
1.714999
3.215563
3.590426
3.980431
2.322387
4.083396
4.710477
-2.125407
-1.061024
0.805397
1.035138
-0.776752
-0.714633
1.382434
-0.515985
1.118183
-1.109093
-0.569284
-2.175357
-1.603592
-1.464366
-2.665950
-1.276713
-1.689381
-1.229244
-0.135333
-1.627178
-3.213479
-3.665255
-3.583506
-1.666492
-3.803138
-3.752568
-4.288583
-4.224554
-2.738351
-5.289937
-5.804072
-5.393271
-5.831136
-0.821661
-1.069895
S26
H
H
C
H
H
H
N
O
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
S
O
S
O
4.362931
3.833313
2.605848
3.514090
2.326854
1.812272
3.112687
3.883107
-3.594229
-3.778559
-4.270406
-1.236505
-0.174505
-1.322980
-4.041804
-1.558770
-4.817514
-5.207873
-5.680739
-4.214974
-5.000342
-4.530924
-5.891568
-5.339768
-1.638879
-0.681558
-2.399538
-1.882585
-0.428797
-0.312654
0.534564
-0.596869
-2.875458
-3.080792
-1.829729
-1.820553
2.335950
2.283261
3.052388
4.222568
5.993279
6.557844
6.255889
6.354748
4.165799
4.917574
-2.766322
-3.775192
-2.111906
-3.373687
-3.128723
-4.365729
-2.777042
-3.556184
-1.493426
-1.531208
-1.362149
-0.586836
-3.964603
-4.926171
-3.877737
-4.011913
-5.061442
-5.556730
-5.573026
-5.233077
-2.956752
-1.879800
-3.419023
-3.127707
-2.941464
-2.765213
-0.641480
-0.507712
1.162914
1.465344
-0.967506
0.245967
-1.528432
-1.771972
-0.501178
-2.193841
-3.107890
-3.695912
1.336649
0.934417
0.766541
1.846776
1.733734
1.376975
2.820928
3.357889
3.184288
4.208855
2.520814
3.110809
3.060422
2.829257
2.427611
4.102243
3.692748
3.491358
3.093977
4.748134
4.222885
4.083214
3.975672
5.293150
3.755175
4.951834
1.388515
2.879662
-0.795682
0.665951
Structure 5 (S5)
H
-0.330944
C
-0.024475
C
0.127013
C
1.999265
C
-0.194861
H
-0.514116
H
-0.682593
H
-0.050421
C
-1.697019
H
-2.311842
H
-1.954404
C
0.661919
2.054427
1.786766
-0.058683
2.035120
0.264271
0.516224
2.352102
-1.110658
0.006956
0.600495
0.358963
-0.505524
-1.568359
-0.548925
1.133065
1.414156
-0.340481
1.809490
0.118160
1.361662
-0.640181
0.048601
-1.645596
-1.367211
S27
H
H
S
C
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
1.725723
0.421630
0.532063
-1.265358
-1.477582
-1.419089
-0.633305
-1.510487
-0.660422
-1.491274
-2.771520
-2.801547
-4.031197
-4.909849
-3.834915
-4.322521
-2.597275
-3.484116
-1.752503
-2.390495
-3.992723
-4.855634
-4.325473
-3.766114
-2.538350
-3.420986
-2.308102
-1.699242
3.496706
3.721655
4.150081
1.046253
0.572470
0.209140
3.959603
1.691151
4.562347
5.042557
5.325786
3.810991
5.133034
4.798305
5.899057
5.632817
1.971103
1.045300
2.673552
2.378685
0.638447
0.420502
-0.307031
0.973730
-0.284211
-0.190278
-2.308652
-2.575215
-4.101005
-4.406659
-4.606158
-2.173933
-2.547432
-1.085377
-4.683530
-2.733091
-1.864091
-2.154001
-0.809584
-1.910093
-2.590099
-2.904930
-3.194995
-1.548282
-4.521766
-5.091950
-3.493351
-4.901691
-6.215982
-6.732357
-6.662026
-6.440389
2.417796
3.269236
1.621795
2.799758
2.088399
3.246931
2.825476
3.910558
1.617288
1.928650
1.114079
0.874823
3.834047
4.780244
3.418831
4.064422
5.188416
5.573897
5.037191
5.984423
4.285714
3.438000
4.590704
5.118738
-1.240201
-2.388648
-1.271230
-1.686770
-1.544421
-0.489858
-2.040645
-3.151711
-3.744066
-3.278824
-2.177099
-3.813381
-3.467747
-4.055875
-3.696998
-2.421333
-5.348898
-5.911467
-5.700611
-5.621835
-1.246306
-1.610473
-1.129570
-0.242780
-2.308195
-2.703744
-1.333201
-2.978118
1.624862
0.968018
1.238586
2.355826
3.045557
1.809174
3.054543
3.224494
3.803792
4.739949
3.199447
4.074830
2.872951
2.436656
2.206427
3.821126
2.409845
1.966262
1.590174
3.043618
4.304184
4.965062
3.839855
4.932795
S28
S
O
S
O
N
O
N
O
S
O
1.860097
1.936043
-2.329924
-2.088907
-2.936594
-4.204687
2.858552
3.375194
1.658166
1.578959
0.192128
-0.114329
-1.675197
-2.175891
-4.170941
-4.594173
3.326117
4.277999
2.423142
3.912395
1.625009
3.088996
-0.499966
0.888952
-3.545466
-4.033635
3.890591
4.814395
-0.389395
-0.537891
Structure 6 (S6)
H
-0.285079
C
0.036513
C
0.331212
C
2.112287
C
-0.083344
H
-0.280147
H
-0.649723
H
0.196209
C
-1.598583
H
-2.178107
H
-1.916707
C
0.719638
H
1.789306
H
0.437326
S
0.589291
C
-1.223345
C
-1.427984
H
-1.307481
H
-0.615272
C
-1.551241
H
-0.738623
H
-1.534387
C
-2.758138
C
-2.880471
C
-4.084633
H
-4.996463
H
-3.896801
H
-4.316710
C
-2.766292
H
-3.685545
H
-1.945412
H
-2.572888
C
-3.921172
H
-4.803641
H
-4.248065
H
-3.633818
C
-2.535318
H
-3.440610
H
-2.248186
H
-1.737832
2.081226
1.790978
-0.144250
1.991997
0.252190
0.370121
2.302444
-1.212722
-0.013149
0.542532
0.381339
-0.473306
-0.280174
-0.108393
-2.285127
-2.536087
-4.067557
-4.426203
-4.545414
-2.064235
-2.410047
-0.970925
-4.619278
-2.589345
-1.737541
-1.994650
-0.672763
-1.838485
-2.371183
-2.658053
-2.958140
-1.317232
-4.507306
-5.063460
-3.486953
-4.933286
-6.142592
-6.639526
-6.637495
-6.331060
-1.465400
-0.456708
1.127206
1.468998
-0.303695
1.875799
0.226679
1.303826
-0.528637
0.219970
-1.500383
-1.406637
-1.313715
-2.400102
-1.390859
-1.715044
-1.638069
-0.605640
-2.208535
-3.142178
-3.800369
-3.218441
-2.221399
-3.753621
-3.293842
-3.845627
-3.478247
-2.236471
-5.289560
-5.813752
-5.719530
-5.522820
-1.211838
-1.549952
-1.027015
-0.242974
-2.444246
-2.812570
-1.508722
-3.173459
S29
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
S
O
S
O
N
O
N
O
S
O
3.579528
3.800318
4.286233
1.181999
1.109333
0.150733
3.940858
1.626655
3.974012
4.439002
4.557498
2.979259
5.403924
5.518934
6.095641
5.736275
1.425791
0.443831
2.188652
1.465200
0.685761
0.753210
-0.359579
0.927673
2.083873
2.295002
-2.215697
-1.892600
-3.005915
-4.304522
2.986072
3.538729
1.654271
2.600277
2.462169
3.299985
1.677085
2.604107
1.927302
2.677266
2.958008
3.993991
1.821852
2.158848
0.968319
1.464029
3.485197
4.285860
2.682816
3.871664
5.071408
4.968747
5.017760
6.085696
4.364257
3.633505
4.394702
5.348769
0.136356
-0.310205
-1.701060
-2.259551
-4.038620
-4.434627
3.955009
5.259848
2.553709
1.938910
1.695528
1.017890
1.391106
2.533641
3.394819
2.171814
3.118204
3.063909
4.161167
5.096618
3.798184
4.434934
3.057253
2.317272
2.773195
4.028259
1.967636
1.491340
1.185992
2.383377
4.235447
5.050507
3.906285
4.653430
1.513866
2.928481
-0.425075
0.924745
-3.549577
-3.977758
3.639411
3.520813
-0.250396
-1.234733
Structure 7 (S7)
H
-0.233764
C
0.070253
C
0.235339
C
2.020233
C
-0.097371
H
-0.466609
H
-0.594470
H
0.127584
C
-1.609237
H
-2.207139
H
-1.879076
C
0.719575
H
1.786312
H
0.439405
S
0.568237
C
-1.241460
2.051041
1.804112
-0.038624
2.145771
0.286195
0.470112
2.377105
-1.105068
0.038951
0.658506
0.366868
-0.507087
-0.284282
-0.207109
-2.312612
-2.567179
-1.671108
-0.645723
1.066327
1.330197
-0.406810
1.735278
0.008920
1.272580
-0.679257
0.001677
-1.689503
-1.448978
-1.377187
-2.465211
-1.331245
-1.674572
S30
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
S
O
N
O
-1.465329
-1.373387
-0.644681
-1.531460
-0.707503
-1.501385
-2.786991
-2.851469
-4.057282
-4.958035
-3.853597
-4.316377
-2.698574
-3.608086
-1.873950
-2.488617
-3.972540
-4.852370
-4.293318
-3.712747
-2.575053
-3.476551
-2.315421
-1.762548
3.490766
3.673140
4.192659
1.016694
0.369053
0.328405
3.893361
1.632929
4.439583
4.864730
5.233765
3.663587
5.071314
4.762203
5.873597
5.515220
1.988432
1.086528
2.673987
2.440366
0.522459
0.249854
-0.387591
0.833480
-2.258650
-1.984488
-2.996879
-4.288917
-4.086805
-4.368480
-4.613584
-2.199481
-2.600004
-1.114973
-4.668424
-2.756830
-1.862828
-2.151757
-0.816213
-1.883702
-2.654357
-2.971340
-3.278777
-1.622365
-4.471902
-5.044142
-3.437940
-4.827161
-6.206028
-6.720972
-6.632648
-6.455091
2.579110
3.519321
1.876513
2.935343
2.227664
3.529093
2.794504
3.893457
1.486598
1.662824
1.056705
0.725702
3.807416
4.802425
3.472809
3.914945
5.260415
5.760317
5.192208
5.929532
4.156568
3.238289
4.540150
4.895842
-1.629114
-2.094075
-4.185831
-4.601454
-1.489347
-0.430459
-2.002486
-3.140369
-3.751772
-3.296457
-2.062794
-3.743473
-3.377833
-3.932075
-3.635015
-2.322140
-5.288138
-5.811981
-5.653290
-5.593982
-1.093110
-1.410642
-0.992432
-0.088607
-2.166857
-2.519410
-1.190553
-2.860445
1.598241
1.061363
1.126147
2.206511
2.739203
1.593377
3.083126
3.262475
3.699019
4.694931
3.077896
3.821182
3.094366
2.760339
2.425395
4.090826
2.642373
2.268538
1.797373
3.383347
4.317314
4.851548
3.840536
5.064482
-0.475748
0.920230
-3.435915
-3.865316
S31
N
O
S
O
S
O
2.740288
3.201524
1.742077
1.646293
1.909963
2.899725
3.184530
3.960747
2.462860
3.948778
0.328745
-0.363832
3.909727
5.006951
-0.484267
-0.672479
1.655430
0.769761
Structure 8 (S8)
H
-0.355251
C
-0.044218
C
0.077923
C
2.013077
C
-0.238623
H
-0.532748
H
-0.681708
H
-0.163909
C
-1.741657
H
-2.341837
H
-2.026963
C
0.587520
H
1.656226
H
0.325107
S
0.438089
C
-1.390147
C
-1.566715
H
-1.620910
H
-0.650142
C
-1.638978
H
-0.716207
H
-1.762992
C
-2.732064
C
-2.787919
C
-4.141719
H
-4.875312
H
-4.031676
H
-4.599491
C
-2.437019
H
-3.215508
H
-1.496571
H
-2.322772
C
-4.049555
H
-4.827886
H
-4.461398
H
-3.903489
C
-2.356173
H
-3.150227
H
-2.180376
H
-1.441999
C
3.524534
H
3.765632
H
4.146670
C
1.096605
2.116758
1.853107
0.025375
2.055668
0.337737
0.641846
2.438500
-1.012253
0.080864
0.696667
0.394084
-0.460844
-0.249260
-0.167025
-2.260752
-2.522513
-4.052299
-4.324904
-4.536719
-2.087549
-2.305296
-1.003374
-4.733057
-2.786454
-2.073196
-2.398056
-0.988636
-2.248942
-2.607330
-3.015851
-3.109822
-1.545965
-4.694663
-5.302954
-3.700092
-5.102571
-6.242911
-6.832915
-6.670092
-6.393491
2.392184
3.235609
1.575673
2.855372
-1.520856
-0.501986
1.198627
1.443655
-0.276037
1.867105
0.168001
1.448586
-0.542912
0.139571
-1.552068
-1.306847
-1.208319
-2.329358
-1.160358
-1.574784
-1.412203
-0.348183
-1.784737
-3.026892
-3.586810
-3.111385
-2.180125
-3.810581
-3.621396
-4.369335
-3.738086
-2.654552
-5.319720
-5.974977
-5.577751
-5.571392
-1.382389
-1.858064
-1.259956
-0.374793
-2.280707
-2.753612
-1.285992
-2.868195
1.630406
0.969015
1.235546
2.393076
S32
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
S
O
0.604830
0.270339
4.020034
1.789760
4.598839
5.096161
5.343179
3.831417
5.218544
4.905092
5.963268
5.737576
2.102500
1.183851
2.783330
2.550872
0.764260
0.526555
-0.176410
1.135459
-2.782961
-3.916979
2.944443
3.501751
1.657235
1.613484
-2.331769
-3.789986
1.819249
1.888849
2.162611
3.330356
2.786220
3.943138
1.560047
1.855300
1.039900
0.835690
3.761455
4.717217
3.325472
3.976589
5.211260
5.631934
5.035686
5.990018
4.353098
3.513064
4.689634
5.174309
-4.232110
-4.802604
3.316252
4.243539
2.449567
3.940301
-1.613978
-1.592678
0.215835
-0.086778
3.088978
1.852920
3.052794
3.253790
3.791860
4.724270
3.178052
4.066894
2.855621
2.424626
2.178310
3.797002
2.436172
2.010000
1.603223
3.063774
4.346930
5.010798
3.894784
4.970885
-3.559381
-4.204435
3.903691
4.828230
-0.358835
-0.505309
-0.279554
-0.600042
1.670347
3.135374
Structure 9 (S9)
H
-0.291629
C
0.030262
C
0.182166
C
2.033291
C
-0.150052
H
-0.492276
H
-0.608442
H
0.013309
C
-1.661805
H
-2.245900
H
-1.969243
C
0.643411
H
1.713902
H
0.351258
S
0.471599
C
-1.366044
C
-1.556207
H
-1.576098
H
-0.659657
C
-1.652274
2.069779
1.833690
0.024847
2.159356
0.323207
0.583234
2.427853
-1.030055
0.066721
0.694092
0.368779
-0.495154
-0.285862
-0.206318
-2.298062
-2.539224
-4.066686
-4.339948
-4.562258
-2.105711
-1.584125
-0.561859
1.182876
1.370333
-0.295255
1.841103
0.099815
1.420783
-0.528801
0.157343
-1.534643
-1.338401
-1.284290
-2.354639
-1.192994
-1.552274
-1.384232
-0.319166
-1.789553
-2.997589
S33
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
-0.752829
-1.755823
-2.757103
-2.839826
-4.172050
-4.939647
-4.046448
-4.594966
-2.539351
-3.347935
-1.617897
-2.414753
-4.045241
-4.841859
-4.450509
-3.865037
-2.404440
-3.221495
-2.200755
-1.512744
3.522979
3.722272
4.190214
1.074851
0.412112
0.396176
3.966677
1.745606
4.494462
4.947556
5.262631
3.703014
5.169927
4.879985
5.948484
5.638098
2.132528
1.239202
2.791372
2.628071
0.668057
0.377179
-0.239200
1.019853
-2.853172
-4.022839
2.842350
3.349019
1.722280
1.659611
1.870553
2.823561
-2.346067
-1.019945
-4.731321
-2.784198
-2.044906
-2.359680
-0.963192
-2.206541
-2.613225
-3.008256
-3.133057
-1.554447
-4.676957
-5.289129
-3.679446
-5.070938
-6.245738
-6.824896
-6.676392
-6.407328
2.549738
3.474010
1.816134
2.998836
2.323499
3.606723
2.778652
3.949732
1.466803
1.647526
1.007309
0.727715
3.760781
4.757860
3.394136
3.873394
5.295274
5.822826
5.191816
5.956444
4.264074
3.362802
4.671139
5.002788
-4.229707
-4.778688
3.210576
3.978361
2.455399
3.940158
0.352116
-0.399350
-3.585734
-3.085804
-2.110656
-3.739682
-3.503251
-4.220716
-3.630421
-2.518329
-5.260436
-5.886889
-5.550626
-5.518002
-1.266911
-1.706109
-1.146139
-0.259372
-2.225227
-2.671633
-1.237356
-2.843526
1.596553
1.038353
1.121462
2.252229
2.807848
1.641961
3.067746
3.281167
3.691801
4.674493
3.059245
3.844429
3.036151
2.691737
2.356020
4.020867
2.634171
2.278133
1.771608
3.354071
4.355913
4.909136
3.893496
5.085340
-3.487214
-4.086339
3.912837
4.995282
-0.442989
-0.650870
1.744502
0.867841
S34
S
O
-2.250430
-3.721899
Structure 10 (S10)
H
-0.292202
C
0.032945
C
0.300701
C
2.135092
C
-0.108756
H
-0.287289
H
-0.636436
H
0.109463
C
-1.624132
H
-2.185889
H
-1.975384
C
0.664873
H
1.738899
H
0.370891
S
0.504150
C
-1.339887
C
-1.519875
H
-1.511016
H
-0.632307
C
-1.663723
H
-0.779288
H
-1.771039
C
-2.737165
C
-2.868530
C
-4.195728
H
-4.981887
H
-4.076479
H
-4.590870
C
-2.608800
H
-3.432724
H
-1.694069
H
-2.493633
C
-4.003136
H
-4.807444
H
-4.411012
H
-3.794595
C
-2.382124
H
-3.208286
H
-2.151553
H
-1.506071
C
3.616804
H
3.851562
H
4.298288
C
1.232360
H
1.146538
H
0.201264
C
4.008588
C
1.724056
-1.620494
-1.595004
-0.226539
-0.478055
2.096770
1.818930
-0.090016
2.001525
0.287165
0.465927
2.354954
-1.147896
0.021217
0.595980
0.382813
-0.472541
-0.297052
-0.123784
-2.283143
-2.513258
-4.049121
-4.390014
-4.512841
-1.990484
-2.190647
-0.901630
-4.672101
-2.625182
-1.907892
-2.180754
-0.819824
-2.132069
-2.356282
-2.713866
-2.852715
-1.282727
-4.678731
-5.268644
-3.693450
-5.132226
-6.174147
-6.727742
-6.666238
-6.291025
2.435266
3.257447
1.627408
2.657451
1.996135
2.757394
2.939692
4.040764
-1.411869
-0.401016
1.216395
1.508530
-0.218672
1.954478
0.280216
1.421427
-0.405133
0.343017
-1.376503
-1.320823
-1.247776
-2.316807
-1.264008
-1.592973
-1.517918
-0.472390
-1.977120
-3.000125
-3.624998
-3.017360
-2.254185
-3.752740
-3.434565
-4.149075
-3.497517
-2.450386
-5.266798
-5.895752
-5.613687
-5.459391
-1.375868
-1.831255
-1.184218
-0.399318
-2.474850
-2.936665
-1.522211
-3.124770
1.710970
1.019193
1.408650
2.570552
3.442586
2.214433
3.122703
3.076307
S35
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
S
O
4.028338
4.514973
4.584287
3.028362
5.482318
5.604185
6.150544
5.838894
1.557367
0.570924
2.315332
1.633074
0.799716
0.845468
-0.245063
1.075269
-2.871358
-4.055087
3.083181
3.671188
-2.190031
-3.668445
2.058533
2.254704
1.671822
2.596362
Structure 11 (S11)
H
-0.420731
C
-0.097762
C
0.054158
C
1.985367
C
-0.283364
H
-0.548109
H
-0.731351
H
-0.183695
C
-1.788172
H
-2.382820
H
-2.090236
C
0.531958
H
1.599559
H
0.240663
C
-1.408611
C
-1.604124
H
-1.680722
H
-0.677777
C
-1.639228
H
-0.708414
H
-1.770208
C
-2.750888
C
-2.771821
C
-4.125764
1.813578
2.147886
0.941582
1.484621
3.431691
4.224194
2.611209
3.817013
5.107365
5.031338
5.016068
6.125878
4.460140
3.740183
4.520161
5.442401
-4.083909
-4.598495
3.962162
5.251249
-1.685262
-1.657091
0.144121
-0.287819
2.548156
1.892783
4.176836
5.102164
3.814533
4.467669
3.035573
2.287938
2.747042
3.998398
1.964290
1.492304
1.181505
2.364334
4.244548
5.070643
3.917673
4.646652
-3.592836
-4.194862
3.647203
3.531958
-0.188444
-0.396153
1.586367
3.007561
-0.217526
-1.196082
2.131919
1.871989
0.051766
2.086862
0.354700
0.669581
2.455185
-0.985313
0.094839
0.696794
0.419473
-0.439179
-0.209818
-0.176615
-2.492412
-4.027304
-4.311921
-4.510213
-2.027554
-2.216965
-0.943067
-4.690465
-2.712808
-1.996901
-1.458495
-0.442360
1.259404
1.479386
-0.211214
1.934096
0.233463
1.516020
-0.460624
0.238731
-1.461168
-1.248014
-1.176189
-2.270047
-1.522434
-1.387132
-0.327829
-1.732719
-2.969683
-3.522617
-3.030339
-2.193030
-3.786312
-3.604385
S36
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
S
O
S
O
-4.860453
-4.014621
-4.579959
-2.396446
-3.166467
-1.454021
-2.273509
-4.085031
-4.850285
-4.504728
-3.958100
-2.374493
-3.158038
-2.221902
-1.447306
3.497489
3.725411
4.117793
1.078029
0.601379
0.240698
4.010387
1.777698
4.603636
5.110805
5.342856
3.842634
5.201620
4.878181
5.939363
5.731908
2.073943
1.147777
2.743957
2.527745
0.765279
0.540233
-0.182879
1.141302
-2.775407
-3.903565
2.943472
3.508250
-2.357525
-3.816751
1.801952
1.892177
1.600972
1.540073
0.434693
1.271870
-2.328746
-0.913775
-2.157618
-2.507533
-2.900233
-3.009391
-1.442336
-4.664469
-5.273321
-3.672534
-5.078516
-6.198282
-6.777730
-6.645411
-6.338234
2.429978
3.275637
1.616985
2.879885
2.183254
3.349883
2.823654
3.970365
1.598095
1.892932
1.083083
0.869522
3.804647
4.759882
3.373541
4.020101
5.240742
5.658191
5.069253
6.020407
4.374494
3.532666
4.707405
5.196596
-4.162751
-4.714770
3.346672
4.273077
-1.608082
-1.605078
0.245100
-0.067283
2.482260
3.972980
-2.236578
-2.841193
-4.347956
-3.734128
-2.633359
-5.285882
-5.960512
-5.537907
-5.516405
-1.422240
-1.918099
-1.303318
-0.414602
-2.315058
-2.817604
-1.325286
-2.884522
1.645297
0.982098
1.240468
2.442890
3.145458
1.915416
3.061670
3.294911
3.790180
4.717393
3.165941
4.072046
2.850992
2.426263
2.163013
3.785999
2.474892
2.062035
1.632387
3.097451
4.402326
5.068329
3.963332
5.022206
-3.562307
-4.234246
3.927760
4.848142
-0.214139
-0.527055
1.702319
3.163611
-0.317792
-0.456867
-1.052697
-2.139349
S37
Structure 12 (S12)
H
-0.459460
C
-0.144173
C
0.027895
C
1.911719
C
-0.277951
H
-0.640769
H
-0.824301
H
-0.165840
C
-1.779905
H
-2.389546
H
-2.079815
C
0.548505
H
1.613485
H
0.262823
C
-1.396257
C
-1.591369
H
-1.650250
H
-0.671747
C
-1.636305
H
-0.715409
H
-1.749018
C
-2.752924
C
-2.787385
C
-4.129944
H
-4.879842
H
-4.008120
H
-4.570672
C
-2.433328
H
-3.217610
H
-1.499898
H
-2.303544
C
-4.074441
H
-4.839338
H
-4.507303
H
-3.925884
C
-2.380393
H
-3.171611
H
-2.214531
H
-1.461679
C
3.421613
H
3.627815
H
4.041928
C
1.024717
H
0.443995
H
0.261804
C
3.946928
C
1.770477
C
4.435976
H
4.943115
H
5.149104
H
3.614973
2.145851
1.918337
0.124015
2.222042
0.398103
0.710936
2.478143
-0.922399
0.110664
0.720349
0.411565
-0.410919
-0.193231
-0.155134
-2.474123
-4.008519
-4.290748
-4.493668
-2.023337
-2.234776
-0.938145
-4.671792
-2.701473
-1.968723
-2.295246
-0.887591
-2.119623
-2.510108
-2.899841
-3.022978
-1.447806
-4.642566
-5.274797
-3.653669
-5.027032
-6.180353
-6.759829
-6.625589
-6.322742
2.568060
3.474626
1.805295
3.059818
2.380333
3.626098
2.808978
4.049523
1.488567
1.670470
0.973715
0.796476
-1.485291
-0.458979
1.283611
1.462818
-0.200794
1.923770
0.193765
1.539392
-0.460037
0.219949
-1.468281
-1.224404
-1.152322
-2.249947
-1.483829
-1.341639
-0.280532
-1.701629
-2.934181
-3.495684
-3.010084
-2.126504
-3.729252
-3.530418
-4.261040
-3.667058
-2.551681
-5.235663
-5.895436
-5.498739
-5.475563
-1.333719
-1.800276
-1.237886
-0.317471
-2.250788
-2.741166
-1.262304
-2.833231
1.618364
1.033864
1.125930
2.425958
3.065123
1.875825
3.060071
3.359304
3.694891
4.650584
3.040931
3.903068
S38
C
5.193974
H
4.930294
H
5.914531
H
5.721616
C
2.131450
H
1.223844
H
2.750331
H
2.663001
C
0.769347
H
0.501969
H
-0.160017
H
1.178013
N
-2.804545
O
-3.955997
N
2.895679
O
3.489817
S
-2.329996
O
-3.797394
S
0.447332
O
1.256654
S
1.478001
O
2.426160
S
1.708417
O
2.651211
Structure 13 (S13)
H
-0.385624
C
-0.035229
C
0.262978
C
2.102507
C
-0.153904
H
-0.314630
H
-0.695552
H
0.050022
C
-1.663947
H
-2.225965
H
-2.028214
C
0.626732
H
1.699403
H
0.331638
C
-1.351086
C
-1.534755
H
-1.532360
H
-0.633321
C
-1.680391
H
-0.788114
H
-1.797008
C
-2.735854
C
-2.872329
C
-4.209807
H
-4.990620
H
-4.105103
H
-4.603638
3.727749
4.730111
3.308561
3.838073
5.357321
5.870880
5.208652
6.051329
4.428483
3.557296
4.830661
5.191994
-4.150308
-4.691680
3.323653
4.145272
-1.587976
-1.603052
-2.214726
-2.836772
2.671914
2.023661
0.427036
-0.393342
2.938623
2.586301
2.225774
3.893094
2.625985
2.286118
1.741024
3.286996
4.485841
5.096149
4.064970
5.157830
-3.497442
-4.139356
3.952500
4.946705
-0.172432
-0.443930
-1.032435
-2.132089
-0.286566
-1.242638
1.848037
1.029554
2.080893
1.805834
-0.072351
2.026474
0.268037
0.515372
2.334399
-1.114216
-0.007367
0.539235
0.380262
-0.461996
-0.281664
-0.091349
-2.490572
-4.034186
-4.404137
-4.477344
-1.926460
-2.088421
-0.838621
-4.642175
-2.547483
-1.857354
-2.122328
-0.766475
-2.111034
-1.328421
-0.325131
1.301980
1.538219
-0.140781
2.024143
0.370787
1.551309
-0.319877
0.448958
-1.276420
-1.254151
-1.170944
-2.241797
-1.587223
-1.562652
-0.527176
-2.014390
-2.979836
-3.604415
-2.959957
-2.331788
-3.761500
-3.427907
-4.151141
-3.462559
-2.450505
S39
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
S
O
S
O
-2.605607
-3.421584
-1.683336
-2.500563
-4.012038
-4.810617
-4.421825
-3.814595
-2.365625
-3.181784
-2.141728
-1.481124
3.589930
3.812634
4.261682
1.226311
1.157414
0.187585
4.014144
1.732871
4.046793
4.558154
4.585490
3.050974
5.490048
5.604955
6.146413
5.866853
1.530594
0.530651
2.265172
1.616156
0.843353
0.914397
-0.210773
1.130075
-2.855677
-4.021185
3.108611
3.697977
-2.208749
-3.685908
1.600318
2.508308
2.023111
2.227421
0.518078
0.840413
Structure 14 (S14)
H
-0.467794
C
-0.959743
-2.221984
-2.565236
-2.696095
-1.141095
-4.686732
-5.256164
-3.710756
-5.182458
-6.133236
-6.678234
-6.654091
-6.221861
2.458000
3.266273
1.641822
2.704938
2.060511
2.801432
2.987649
4.096116
1.885503
2.235504
0.999782
1.573850
3.465051
4.236962
2.631857
3.872154
5.143862
5.058621
5.040015
6.169119
4.534994
3.829316
4.589026
5.524089
-4.010157
-4.519002
4.030943
5.312465
-1.720470
-1.698585
2.551297
1.898256
0.169800
-0.218178
-2.266203
-2.803641
-5.263414
-5.910436
-5.621419
-5.416886
-1.470007
-1.960092
-1.238856
-0.511782
-2.596590
-3.085598
-1.657739
-3.239513
1.700457
0.988495
1.398772
2.609578
3.495363
2.274923
3.093244
3.078683
4.172025
5.078034
3.817059
4.494081
2.966829
2.196885
2.687630
3.912848
1.954232
1.513229
1.150867
2.334647
4.266601
5.103166
3.970109
4.643401
-3.651539
-4.291104
3.611580
3.432548
-0.159057
-0.380690
-0.182930
-1.178576
1.658040
3.091111
-1.297463
0.062433
-2.482136
-1.704004
-0.910243
-0.315764
S40
C
C
C
H
H
H
C
H
H
C
H
H
C
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
-0.694387
-3.282240
0.034298
-1.141643
-1.316900
-0.010674
1.108958
0.654216
1.555516
0.682839
-0.060060
1.176025
3.268081
4.343431
3.964008
4.491764
3.846027
3.951222
3.148370
5.722347
5.211889
5.076906
6.062700
4.422643
4.660907
5.836671
6.793028
6.007843
5.163457
5.762361
6.786456
5.121882
5.434521
6.748051
7.739854
6.452590
6.802462
-4.464049
-4.743647
-4.144575
-3.753628
-3.718574
-3.065696
-5.762603
-5.168734
-5.622084
-6.612177
-5.218383
-4.960046
-6.864532
-7.014392
-6.582592
0.544837
0.026201
-0.559814
0.145573
-2.180142
1.337477
-1.214605
-1.566921
-2.086405
-0.050935
0.369485
-0.863616
0.352654
1.419603
2.174031
1.924806
-0.757868
-0.299327
-1.592164
0.926088
-1.351342
-2.425041
-2.842556
-3.233022
-2.027971
-2.016300
-2.475212
-1.276380
-2.788647
0.634041
0.388608
-0.201217
1.519276
2.038865
1.742019
2.961657
2.237920
0.529974
-0.266330
1.365491
-0.458645
0.415232
-1.191637
0.939123
-1.078394
2.237166
2.537156
3.042785
2.139173
1.150158
0.259287
1.986575
0.800861
-0.274153
0.007742
1.717136
0.605091
1.114065
0.911767
1.844346
0.418789
-1.298716
-1.981076
-1.841534
-0.116291
0.141493
0.838875
-0.821532
-0.993237
-1.986172
-1.118525
0.633678
-0.573371
0.530218
0.748470
0.181088
1.458623
-1.817880
-1.560467
-2.605979
-2.206095
2.150953
2.442447
2.441611
2.705676
0.334549
0.681035
0.845203
-0.740646
-1.142166
-1.844222
-1.775220
1.102134
1.765287
1.536133
-0.392764
1.156557
0.431542
0.790689
-0.189670
1.291795
-1.439669
-2.056033
-2.088637
S41
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
S
O
S
O
-7.815869
-5.237045
-4.430391
-5.144643
-6.193145
-5.565127
-5.538657
-4.879335
-6.579597
6.151669
7.337865
-6.174235
-7.327540
-2.476492
-2.036032
-2.026633
-2.577902
2.538442
1.994620
1.916203
2.499000
Structure 15 (S15)
H
-2.125202
C
-1.845036
C
0.067054
C
-2.035661
C
-0.309319
H
-0.481611
H
-2.371850
H
1.126866
C
-0.038543
H
-0.597536
H
-0.410797
C
0.436799
H
0.236744
H
0.117936
C
2.476428
C
4.016347
H
4.367057
H
4.478097
C
1.927926
H
2.097483
H
0.840377
C
4.625525
C
2.553407
C
1.838279
H
2.120391
H
0.750390
H
2.050810
C
2.260764
H
2.606188
1.385968
-2.450570
-3.098219
-2.360476
-2.930461
-1.254284
-0.296187
-1.947310
-1.656102
-0.277218
-0.701613
-0.169219
-0.708969
-1.327019
-0.682293
1.451553
2.399022
-0.196151
1.050407
1.311285
1.535028
-0.959831
0.450811
0.812342
-0.634384
0.663982
2.636481
3.165634
3.137407
2.700674
-0.138309
0.152900
0.531666
0.353379
-1.314056
-2.611969
-0.098137
0.947197
1.515680
2.188225
-1.087604
-2.467790
-0.354027
-0.016605
0.287969
2.108099
-0.145111
-0.293804
-0.683340
0.105853
-1.661206
-2.215402
-2.031296
0.613824
1.685610
0.280326
-1.349289
-1.543977
-1.549299
-0.646448
-1.666695
-0.776830
-1.783586
-2.747706
-2.859539
-4.188521
-4.977780
-4.073466
-4.574596
-2.585081
-3.404014
-1.348590
-0.342393
1.260485
1.545988
-0.166742
2.008801
0.348688
1.464355
-0.332910
0.432532
-1.293110
-1.284120
-1.243720
-2.276505
-1.551776
-1.499359
-0.457241
-1.937453
-2.952267
-3.574966
-2.946032
-2.264287
-3.729058
-3.411030
-4.118290
-3.486234
-2.420739
-5.235824
-5.877939
S42
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
S
O
S
O
2.753593
1.184575
4.646110
5.238624
3.664320
5.103910
6.123262
6.668511
6.632187
6.228595
-2.480847
-3.311929
-1.682297
-2.674240
-2.003913
-2.770051
-2.974306
-4.056346
-1.836000
-2.164464
-0.974306
-1.492933
-3.482956
-4.286287
-2.673414
-3.859569
-5.131715
-5.054118
-5.051904
-6.147048
-4.459060
-3.731962
-4.515132
-5.439440
4.014387
4.514851
-3.979927
-5.275833
-2.589509
-1.945247
-0.176364
0.272501
2.247374
2.804157
1.675747
1.669099
Structure 16 (S16)
H
-2.130277
C
-1.886109
C
-0.076357
C
-2.193419
-1.668006
-2.465670
-4.026272
-4.820063
-4.443857
-3.829020
-2.389305
-3.207897
-2.173934
-1.503023
3.588168
3.806215
4.272794
1.212342
1.141608
0.176742
3.993856
1.699550
4.039083
4.533839
4.599426
3.046231
5.460832
5.563513
6.133403
5.827186
1.516227
0.525715
2.266960
1.590002
0.783377
0.841451
-0.264748
1.056164
-2.865805
-4.047258
3.064322
3.639564
1.617475
2.535848
2.048337
2.264266
0.515078
1.277243
-2.203329
-3.682691
-5.581698
-5.410312
-1.403969
-1.874295
-1.214012
-0.427130
-2.505787
-2.990437
-1.558444
-3.143719
1.732988
1.046463
1.413520
2.623820
3.490387
2.279688
3.144750
3.137121
4.184950
5.108047
3.805174
4.483952
3.043207
2.304298
2.734587
4.005801
2.036340
1.573212
1.245429
2.444711
4.317605
5.136639
4.000899
4.726108
-3.593445
-4.212829
3.693997
3.595231
-0.170651
-1.161702
1.605343
3.017900
-1.183286
-2.348194
-0.132824
-0.329696
-0.390187
-0.055865
0.111300
1.979222
-1.507185
-0.490850
1.241669
1.418341
S43
C
H
H
H
C
H
H
C
H
H
C
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
-0.370790
-0.643283
-2.471095
0.976444
-0.101818
-0.711548
-0.410476
0.424939
0.181176
0.167146
2.487469
4.022336
4.301547
4.504495
2.036147
2.234486
0.952061
4.692953
2.725714
2.005947
2.339564
0.923663
2.161578
2.532388
2.929603
3.037109
1.469134
4.666948
5.291048
3.677289
5.063104
6.200295
6.784655
6.641790
6.340526
-2.568122
-3.490463
-1.827658
-3.031398
-2.354328
-3.636837
-2.791788
-3.981857
-1.473726
-1.648127
-1.007755
-0.742367
-3.761697
-4.762122
-3.388361
-3.868103
-5.322364
-0.224668
-0.553341
-0.688837
-0.066221
-1.732838
-2.322809
-2.050185
0.569888
1.634493
0.240938
-1.374512
-1.560220
-1.596737
-0.645814
-1.652919
-0.742767
-1.781308
-2.733967
-2.814528
-4.159924
-4.920626
-4.051220
-4.580497
-2.493112
-3.287156
-1.560711
-2.377812
-4.039030
-4.815907
-4.464710
-3.871173
-2.357567
-3.156716
-2.168394
-1.450948
3.476258
3.676833
4.127634
1.042607
0.396874
0.345170
3.946507
1.739138
4.470431
4.939843
5.224501
3.673787
5.158830
4.872753
5.921954
5.644817
2.124308
-0.236314
1.902551
0.184578
1.482735
-0.466714
0.230048
-1.467279
-1.292320
-1.267660
-2.304681
-1.511673
-1.361515
-0.298627
-1.738481
-2.955225
-3.538327
-3.023922
-2.121155
-3.725713
-3.500439
-4.216564
-3.638907
-2.513574
-5.239280
-5.882708
-5.521104
-5.482358
-1.301743
-1.759201
-1.184716
-0.292949
-2.248880
-2.720213
-1.262904
-2.850485
1.620986
1.060072
1.134627
2.325485
2.899192
1.734176
3.084835
3.337092
3.698799
4.674945
3.054130
3.861584
3.034010
2.695962
2.340178
4.010751
2.679409
S44
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
S
O
S
O
-5.854014
-5.212454
-5.982787
-4.307353
-3.409875
-4.720429
-5.045082
4.174222
4.727967
-3.234455
-3.997802
2.225161
2.828237
1.599926
1.609493
-0.383765
0.378396
-2.513761
-4.000937
Structure 17 (S17)
H
-0.381285
C
-0.118946
C
0.055956
C
1.966921
C
-0.285347
H
-0.608224
H
-0.805054
H
-0.098072
C
-1.788742
H
-2.395166
H
-2.065553
C
0.500206
H
1.577023
H
0.223969
C
-1.489694
C
-1.667036
H
-1.691342
H
-0.749923
C
-1.800875
H
-0.884641
H
-1.988053
C
-2.843820
C
-2.923740
C
-4.302351
H
-4.994745
H
-4.214168
H
-4.802004
C
-2.555797
H
-3.312400
H
-1.598595
H
-2.467128
1.228863
2.769761
2.634781
0.684377
0.396772
-0.228138
1.055610
-2.812956
-3.969104
2.841254
3.372921
0.484942
1.270146
-2.283527
-3.754245
1.806371
2.728120
1.636333
1.562859
2.335036
1.807680
3.389528
4.430998
4.992042
3.984544
5.151740
-3.491777
-4.113664
3.949242
5.022328
-1.107005
-2.234063
-0.180553
-0.433087
1.784270
0.884777
-0.385143
-0.569385
2.210248
1.944487
0.132457
2.280385
0.418382
0.708507
2.502834
-0.910771
0.171932
0.730985
0.558199
-0.376715
-0.232019
-0.047996
-2.482617
-4.004185
-4.221339
-4.496265
-2.098006
-2.250772
-1.020307
-4.719867
-2.880135
-2.194804
-2.547681
-1.109873
-2.375814
-2.794981
-3.269442
-3.287995
-1.750275
-1.518735
-0.486222
1.209508
1.498065
-0.265653
1.865835
0.163098
1.483303
-0.531831
0.193672
-1.521265
-1.325100
-1.244850
-2.334557
-1.664378
-1.427333
-0.351213
-1.785069
-3.130201
-3.713341
-3.209959
-2.127007
-3.878583
-3.759904
-4.534372
-3.888752
-2.812619
-5.392367
-6.028616
-5.602954
-5.714306
S45
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
O
S
O
O
S
O
O
S
O
O
-4.144692
-4.967468
-4.483053
-4.008773
-2.493174
-3.305273
-2.305210
-1.591813
3.474949
3.647462
4.084953
1.077954
0.490743
0.310277
4.042617
1.830013
4.681322
3.953026
5.177623
5.440412
5.211772
4.864909
5.930144
5.771208
2.139845
1.211796
2.727407
2.682665
0.852380
0.623354
-0.097805
1.261007
-2.898222
-4.032599
2.992021
3.587546
0.286512
1.056672
0.593727
-2.420959
-2.207082
-3.777621
1.486568
2.391590
1.292078
1.718406
2.633886
1.715532
Structure 18 (S18)
H
-2.375218
C
-2.101843
-4.592988
-5.153397
-3.570923
-5.002122
-6.237484
-6.845697
-6.596669
-6.443720
2.635352
3.535465
1.870255
3.090973
2.397627
3.663721
2.909104
4.054193
1.629735
0.839761
1.833725
1.221627
3.923503
4.907240
3.565671
4.064037
5.394094
5.901929
5.282044
6.075706
4.368523
3.469697
4.761954
5.118056
-4.306438
-4.923666
3.336046
4.145135
-2.146858
-2.650921
-2.615442
-1.487348
-1.975807
-1.339599
2.653424
2.011042
4.089434
0.506331
-0.223520
0.270635
-1.312100
-1.770486
-1.184081
-0.303310
-2.126342
-2.541875
-1.107281
-2.716666
1.616868
1.011627
1.118666
2.482190
3.097469
1.947405
3.034773
3.436549
3.619440
3.804498
4.576274
2.941758
2.870407
2.541540
2.122476
3.802641
2.738654
2.449081
1.826637
3.403187
4.602344
5.187655
4.221551
5.289849
-3.534837
-4.134142
3.972881
4.979549
-1.311226
-2.433305
0.021383
-0.475451
0.868010
-0.958956
-0.218422
-1.145233
-0.311064
1.750488
0.903558
3.181076
-0.497759
-0.145717
-1.590262
-0.587851
S46
C
C
C
H
H
H
C
H
H
C
H
H
C
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
-0.225918
-2.376336
-0.571188
-0.751321
-2.662155
0.840221
-0.324633
-0.907783
-0.680713
0.207190
-0.045709
-0.066980
2.362677
3.869838
4.029196
4.370254
2.076840
2.267937
1.010015
4.648363
2.922078
2.253710
2.657148
1.175472
2.395993
2.926121
3.452600
3.415131
1.902377
4.498899
5.119043
3.482349
4.823453
6.157199
6.804270
6.449600
6.383533
-2.697944
-3.672077
-1.980707
-3.271840
-2.686522
-4.079857
-2.785075
-3.929314
-1.444123
-1.521441
-1.147236
-0.620362
-3.815027
-4.831371
-3.549085
0.007798
1.953267
-0.318928
-0.684463
-0.774904
-0.115020
-1.822546
-2.437666
-2.078439
0.507372
1.568451
0.201455
-1.398858
-1.539999
-1.605339
-0.607794
-1.622206
-0.667851
-1.820238
-2.677414
-2.695790
-4.087420
-4.728089
-4.006577
-4.640153
-2.248244
-2.962996
-1.274560
-2.156659
-4.017330
-4.801551
-4.391748
-3.917501
-2.304167
-3.086611
-2.158830
-1.373397
3.464027
3.636340
4.053312
1.098733
0.254759
0.624203
4.044192
1.862965
4.701256
5.192886
5.468826
3.990718
5.211194
4.872319
5.937318
1.090159
1.313595
-0.379097
1.759145
0.113791
1.297850
-0.663861
0.034537
-1.670243
-1.425884
-1.365017
-2.442097
-1.666003
-1.346533
-0.261708
-1.653061
-3.163674
-3.676706
-3.325282
-2.051831
-3.918042
-3.916077
-4.710183
-4.095376
-2.992076
-5.412572
-6.056272
-5.540662
-5.795277
-1.308037
-1.757267
-1.278792
-0.264947
-1.941028
-2.354819
-0.894036
-2.475720
1.430546
0.949995
0.842864
2.241163
2.626729
1.667450
2.869576
3.430647
3.275244
4.252848
2.550608
3.345075
2.839209
2.625647
2.060898
S47
H
C
H
H
H
C
H
H
H
N
O
N
O
S
S
S
O
O
S
O
O
-3.843509
-5.374516
-5.993988
-5.421235
-5.857485
-4.029631
-3.035816
-4.547479
-4.585721
4.324523
4.997451
-3.078583
-3.673399
-2.750420
2.012710
1.329981
1.765357
1.220837
-0.595326
0.203948
-0.447426
5.761048
2.255064
1.360899
2.814870
2.851746
0.855282
0.563580
-0.060197
1.268194
-2.672129
-3.766801
2.985719
3.592124
1.540627
0.423510
-2.462786
-2.311398
-3.789478
1.648624
2.589545
1.567328
3.787115
3.046205
2.903799
2.109006
3.827684
4.606684
4.967387
4.296053
5.456129
-3.484641
-4.098386
3.849600
4.992640
-0.477617
-1.269898
-0.570974
0.803033
-1.139419
1.692233
0.933288
3.132795
-0.433188
-0.072478
0.090430
1.992352
-0.262114
-0.600126
-0.669928
-0.006504
-1.776494
-2.367878
-2.051496
0.522259
1.587140
0.188119
-1.411870
-1.557713
-1.593205
-0.639400
-1.676174
-0.739123
-1.868537
-2.722384
-2.779680
-4.164319
-4.832865
-4.079041
-4.689486
-2.377198
-1.536722
-0.546632
1.079961
1.338019
-0.373291
1.775247
0.182599
1.259395
-0.627863
0.093712
-1.622311
-1.461624
-1.428814
-2.462206
-1.685130
-1.385662
-0.302084
-1.727068
-3.170519
-3.714388
-3.308740
-2.070067
-3.906373
-3.851031
-4.630969
-4.016250
-2.912584
-5.413521
Structure 19 (S19)
H
C
C
C
C
H
H
H
C
H
H
C
H
H
C
C
H
H
C
H
H
C
C
C
H
H
H
C
-2.300374
-1.994055
-0.086188
-2.257724
-0.467753
-0.578139
-2.551550
0.987703
-0.245255
-0.824773
-0.619895
0.296838
0.055123
-0.000858
2.430029
3.940710
4.116974
4.444159
2.117113
2.308482
1.045995
4.697408
2.939945
2.259602
2.645022
1.179452
2.411208
2.922442
S48
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
S
O
O
S
O
O
S
O
3.431572
3.417702
1.893170
4.548169
5.152106
3.528557
4.892703
6.211102
6.844231
6.522085
6.436809
-2.616344
-3.568597
-1.894336
-3.116065
-2.475544
-3.855542
-2.775185
-3.879472
-1.470133
-1.593024
-1.177399
-0.625555
-3.837130
-4.834846
-3.564441
-3.915855
-5.303823
-5.889679
-5.306237
-5.850567
-4.035343
-3.062470
-4.503580
-4.662212
4.349530
5.002972
-3.074085
-3.728315
2.102040
1.405021
1.862225
1.273891
-0.475542
0.268189
-0.273278
-2.581358
-4.067758
Structure 20 (S20)
H
-0.346683
C
-0.103816
-3.115795
-1.412363
-2.287617
-4.038549
-4.841959
-4.401044
-3.911951
-2.360229
-3.160487
-2.187068
-1.447649
3.496387
3.670739
4.121101
1.079676
0.299951
0.520457
4.023497
1.797592
4.704390
5.149711
5.512402
4.018767
5.161765
4.802581
5.921425
5.677667
2.164105
1.259019
2.744189
2.730277
0.758954
0.484451
-0.162123
1.136915
-2.755411
-3.873034
2.923487
3.472904
0.427221
-2.432516
-2.239557
-3.774703
1.734441
2.671875
1.693983
1.633861
1.599167
-6.044119
-5.579065
-5.781588
-1.284991
-1.722212
-1.226406
-0.251251
-1.994877
-2.395966
-0.957516
-2.560305
1.508679
0.988344
0.965154
2.246053
2.676078
1.659117
2.959329
3.396346
3.435263
4.430198
2.754103
3.498424
2.929313
2.666740
2.186113
3.893342
2.924233
2.721507
1.998796
3.686244
4.540038
4.965612
4.172428
5.355830
-3.496852
-4.089377
3.890197
5.028891
-1.336418
-0.541807
0.819789
-1.066242
1.658049
0.840970
3.092381
-0.469577
-0.664075
2.029365
1.807881
-1.575617
-0.528182
S49
C
C
C
H
H
H
C
H
H
C
H
H
C
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
0.046506
1.976377
-0.275288
-0.546285
-0.798043
-0.228238
-1.777561
-2.372883
-2.071067
0.550500
1.619768
0.315165
-1.444005
-1.656396
-1.722497
-0.737789
-1.682510
-0.757454
-1.784767
-2.820042
-2.835481
-4.179945
-4.918900
-4.056329
-4.637257
-2.474086
-3.254980
-1.539508
-2.343212
-4.145751
-4.926886
-4.545200
-4.016769
-2.461997
-3.257775
-2.303207
-1.542899
3.484726
3.682853
4.102209
1.084252
0.661033
0.206203
4.025696
1.784763
4.624360
5.145984
5.352326
3.863580
5.216875
4.886701
5.936601
0.054640
2.091085
0.291515
0.724298
2.396753
-0.953649
0.033430
0.649109
0.351642
-0.530449
-0.356664
-0.232670
-2.551794
-4.085405
-4.366371
-4.576872
-2.100540
-2.321238
-1.013537
-4.740739
-2.772147
-2.042984
-2.357686
-0.959714
-2.212475
-2.576112
-2.963601
-3.088184
-1.512978
-4.695098
-5.285679
-3.696682
-5.119178
-6.253600
-6.827304
-6.695872
-6.408036
2.446061
3.288652
1.636740
2.861072
2.157288
3.285445
2.852299
3.980519
1.630598
1.930992
1.107323
0.907603
3.824054
4.776250
3.382527
1.246150
1.478298
-0.242800
1.879031
0.083776
1.564327
-0.496218
0.190891
-1.501522
-1.254116
-1.125524
-2.281633
-1.541481
-1.399293
-0.338273
-1.756520
-2.992704
-3.547619
-3.067365
-2.186780
-3.791425
-3.598623
-4.345540
-3.714355
-2.630630
-5.296060
-5.961142
-5.556597
-5.531704
-1.403508
-1.896574
-1.271277
-0.400255
-2.302783
-2.792535
-1.311802
-2.881535
1.611251
0.935030
1.196144
2.479377
3.208564
1.977267
3.012045
3.291138
3.741818
4.659156
3.111244
4.039384
2.764447
2.337229
2.064139
S50
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
S
O
O
S
O
S
O
5.769381
2.036231
1.094684
2.707474
2.471857
0.797898
0.607011
-0.168037
1.176881
-2.847993
-3.979441
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-2.370734
-3.829371
1.505317
2.415227
1.328134
1.796145
1.883234
0.411338
0.648119
Structure 21 (S21)
H
-0.412429
C
-0.145871
C
0.077161
C
1.938507
C
-0.268064
H
-0.579848
H
-0.857309
H
-0.081999
C
-1.766530
H
-2.388468
H
-2.040875
C
0.601328
H
1.662089
H
0.360523
C
-1.278374
C
-1.500082
H
-1.448800
H
-0.645070
C
-1.508076
H
-0.650929
H
-1.485036
C
-2.782655
C
-2.789871
C
-4.020533
H
-4.892365
H
-3.816309
H
-4.326141
C
-2.566276
4.046011
5.245116
5.628765
5.080441
6.048130
4.380471
3.543190
4.691560
5.216300
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3.391359
4.353597
-1.652427
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2.512308
1.848128
3.948595
0.248896
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-2.753347
3.684961
2.448443
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-2.085432
-3.700598
-3.361565
-3.965448
-3.574850
-2.319672
-5.231936
S51
H
H
H
C
H
H
H
C
H
H
H
C
H
H
C
H
H
C
C
C
H
H
H
C
H
H
H
C
H
H
H
C
H
H
H
N
O
N
O
S
O
O
S
S
O
S
O
-3.446725
-1.718433
-2.353992
-4.013602
-4.870068
-4.352862
-3.794326
-2.545940
-3.422859
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3.429181
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1.035614
0.637841
0.143389
3.954508
1.721959
4.427685
4.928492
5.141585
3.596563
5.209921
4.948167
5.921088
5.746158
1.963638
1.022696
2.659722
2.366187
0.731318
0.544567
-0.235822
1.104770
-2.936808
-4.208227
2.923109
3.512386
1.426764
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1.166619
1.808346
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-6.440942
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1.536786
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0.990523
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3.732766
4.720874
3.277115
3.878662
5.272760
5.643187
5.145811
6.072775
4.353390
3.499206
4.668467
5.176645
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3.397925
4.350771
2.586254
2.003853
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-5.493621
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-2.895714
1.613442
1.002050
1.128172
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3.221263
2.017598
3.043167
3.331753
3.733184
4.685259
3.106081
3.958880
2.872750
2.478677
2.173042
3.817671
2.519308
2.095739
1.690477
3.151686
4.470794
5.132885
4.061112
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3.930059
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1.025141
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S52