Pt anticancer drugs
A combined solid-state 17O NMR, crystallographic, and
computational study of oxiranes
Andrew Rinald,1 Victor Terskikh,1,2 Gabriele Schatte,1 and Gang
Wu1*
1Department of Chemistry, Queen’s University, 90 Bader Lane,
Kingston, Ontario, Canada K7L 3N6; 2Department of Chemistry,
University of Ottawa, Ottawa, Ontario, Canada K1A 0R6
*Corresponding author: [email protected]
Abstract
We report synthesis and solid-state 17O NMR characterization of
three 17O-labeled oxiranes: (2S*,
3S*)-2,3-bis(4-nitrophenyl)-[17O]oxirane, (2S*,
3R*)-2,3-bis(4-nitrophenyl)-[17O]oxirane, and
2,2,3-triphenyl-[17O]oxirane. In addition, we have determined the
crystal structure of (2S*, 3R*)-2,3-bis(4-nitrophenyl)oxirane by
X-ray crystallography. When the experimentally determined 17O NMR
tensors for oxiranes (where the C-O-C bond angle is about 60) are
compared with those for dimethyl ether (where the C-O-C bond angle
is 113) and other R-O-R functional groups, we found that the highly
constrained geometry of oxiranes results in distinct tensor
orientations in the molecular frame of reference. The experimental
results are complemented by quantum chemical computations. This
study represents the first time that 17O chemical shift and
quadrupole coupling tensors are simultaneously determined for
oxirane compounds.
Keywords: oxirane, solid-state 17O NMR, quadrupole coupling
tensor, chemical shift tensor
1. Introduction
Oxiranes (also known as 1,2-epoxides) are a class of organic
compounds containing a three membered heterocyclic ring of two
carbon atoms and one oxygen atom. Oxiranes are important building
blocks used in organic syntheses. An example of their utility is in
the use of ring opening mechanisms to make regioselective
ethers/alcohols.1 Due to the strain present in the three membered
ring system (containing a sterically unfavourable C-O-C bond angle
of about 60o), oxiranes are very reactive electrophiles that can
serve as useful reaction intermediates. Ring opening of epoxides is
the basis for the formation of epoxy glues and glycols. Oxiranes
are also biologically important molecules. They are present in
numerous biological hormones, notably in many juvenoids and insect
sex pheromones.2-3 An example of oxirane incorporation into insect
sex pheromones is (+/-)-disparlure. Gypsy moth pheromone-binding
proteins enantioselectively recognize (+)-disparlure, whereas
(-)-disparlure cancels the attraction of (+)-disparlure. Clearly
the conformation of the oxirane ring is directly linked to
disparlure function, but the specific source of the
enantioselectivity is unknown.3
The C-O-C bond angle in oxiranes is approximately 60o, which is
highly unusual, because it is considerably smaller than the angle
between orbitals with 100% p-character (90o). Coulson and Moffit4
in 1949 described the bonding in three-membered rings as “bent”, as
depicted in Scheme 1, referring to chemical bonds that contain
hybrid orbitals whose maxima do not lie in the directions of the
bonds. They used this explanation to justify the strain in
non-linear molecules, and how it is possible to have bond angles
smaller than 90o. They defined “strain energy” to be the difference
between the observed heat of formation and that of a strainless
reference compound. More recent calculations suggested the primary
source of strain energy in oxiranes to be due to the distortion of
electron populations within the three-membered ring as compared
with open chain structures.5 Also related to the synthetic utility
of oxiranes is that their bonding properties are much closer to
what are observed for olefins than for typical aliphatic systems.
This was first observed in early electron diffraction studies that
found large bond shortening effects in three membered
oxygen-containing rings.6-7 The carbon hybridization was also found
to be closer to sp2 than sp3. A later UV-Vis spectroscopic study
also found uncharacteristically high π-character for the oxygen
atoms valence electrons in oxiranes.8 Due to the inherent
topological features of three-membered rings, there is a high level
of electron density in the plane of the ring, which leads to a
level of surface delocalization, strengthening the bonds within the
ring. Increasing the electronegativity of the X group in the
three-membered ring (for C2H4X), increases the electron donation to
the X atom and decreases the back-donation to the carbon atoms,
thus the oxygen atom in oxiranes is more nucleophilic than one
would expect, which leads to its utility as a nucleophilic attack
and coordination site.9
Scheme 1. Cartoon representation depicting the formation of bent
bonds in oxiranes.
More recent studies have analyzed the effect that substituting
electron withdrawing groups on oxiranes have on the structural
parameters of the central oxirane ring. Computational and
experimentally derived results suggest that increasing the electron
withdrawing character of oxirane residues (thus removing electron
density from the oxirane ring) lengthens the C-C bond lengths (and
makes the bond less covalent), widens the C-O-C angles, and in
general weakens the C-O bond strength (the effect is additive). It
was also found that by adding asymmetric substituents to the
oxirane ring leads to asymmetric local electron densities within
the oxirane ring that mirror the orientation of the electron
withdrawing ability of the substituents.10
While 1H and 13C NMR studies of oxiranes have been widely
reported,11-21 very limited information about 17O NMR parameters
for oxiranes is available in the literature. In an early microwave
spectroscopic study of ethylene oxide (the smallest oxirane
molecule), Creswell and Schwendeman reported the following 17O
quadrupole coupling (QC) tensor: zz = 12.6, yy = –7.4, and xx =
–5.2 MHz (or CQ = 12.6 MHz and Q = 0.17).22 There were also several
early 17O NMR studies of oxiranes in solution.23-25 Owing to the
unusual oxygen bonding in oxiranes, several computational studies
were aimed at calculating accurate CQ(17O) values.26-29 In
addition, the 17O QC tensor in oxiranes was analyzed with the aid
of the Townes-Dailey model.30-31 Oxiranes were also used to test
magnetically corrected basis sets in magnetic shielding
calculations.32 In the present work, we set out to achieve two
goals. First, we investigated synthetic methods for 17O-labeling of
oxiranes. In this regard, we report herein synthesis of three
representative oxiranes:
(2S*,3S*)-2,3-bis(4-nitrophenyl)-[17O]oxirane (Compound 1),
(2S*,3R*)-2,3-bis(4-nitrophenyl)-[17O]oxirane (Compound 2), and
racemic 2,2,3-triphenyl-[17O]oxirane (Compound 3); see Scheme 2.
The second objective of this study was to experimentally determine
17O chemical shift (CS) and quadrupole coupling (QC) tensors in
these oxiranes. To the best of our knowledge,33-35 no solid-state
17O NMR studies have ever been reported on oxirane compounds.
Scheme 2. Molecular structures of
(2S*,3S*)-2,3-bis(4-nitrophenyl)-[17O]oxirane (Compound 1),
(2S*,3R*)-2,3-bis(4-nitrophenyl)-[17O]oxirane (Compound 2), and
[17O]-2,2,3-triphenyl-[17O]oxirane (Compound 3). Note that Compound
3 prepared in this study is a racemic mixture.
2. Experimental section
Synthesis
All common chemicals and solvents were purchased from
Sigma-Aldrich (Oakville, ON). Oxygen-17 enriched water (40% 17O,
40% 18O, 20% 16O) and oxygen-18 enriched water (97% 18O, 3% 16O)
were purchased from CortecNet (Voisons-Le-Bretonneux, France).
Synthesis of
[17O]-(2S*,3S*)/(2S*,3R*)-2,3-bis(4-nitrophenyl)oxirane.
p-Nitro-[17O]benzaldehyde was first prepared following a literature
method.36 In particular, p-nitrobenzaldehyde (478 mg, 3.14 mmol)
was dissolved in a minimum of dichloromethane and 120 µL 40% H217O
(6.25 mmol). The solution was stirred vigorously for three days at
room temperature. Upon removal of the solvent, the resultant white
powders were further dried in vacuo. (480 mg, 100% yield). 17O NMR
(67 MHz, CH2Cl2), δ = 585 ppm.
(2S*,3S*)/(2S*,3R*)-2,3-Bis(4-nitrophenyl)-[17O]oxirane were
prepared by using a ZnBr2-mediated reaction of
p-nitro-[17O]benzaldehyde with triethyl phosphite as reported by
Raju et al.37 Triethylphosphite (1.05 g, 6.37 mmol) was added to a
mixture of p-Nitro-[17O]benzaldehyde (502 mg, 3.30 mmol) and zinc
bromide (87 mg, 0.33 mmol) under nitrogen atmosphere. After the
solution was stirred for three hours, it was poured over 50 g ice
and left for two hours. The organics were extracted with 2 50 mL
ethyl acetate, then washed with 2 25 mL 20% brine. The solvent was
then removed in vacuo. Isolation of the (2S*,3S*) isomer (or
cis-isomer) was achieved by treating the resultant solid with 10 mL
cold methanol, leaving behind the cis-isomer as a white precipitate
that was collected by filtration. The filtrate was then dried in
vacuo and the (2S*, 3R*) isomer (or trans-isomer) was isolated as a
white powder using silica column chromatography (mobile phase 10%
ethyl acetate: 90% hexanes). The trans compound was recrystallized
from hexanes. (2S*,3S*)-2,3-bis(4-nitrophenyl)-[17O]oxirane: (120
mg, 27% yield). 1H NMR (300 MHz, CDCl3): δ = 8.24 (d, 3JHH = 8.66
Hz, 4H), 7.54 (d, 3JHH = 8.66 Hz, 4H), 3.98 (s, 2H) ppm. 13C NMR
(75.4 MHz, CDCl3): δ = 148.38, 143.22, 126.38, 124.07, 62.06 ppm.
17O NMR (67 MHz, CDCl3) δ = 35 ppm. (2S*,
3R*)-2,3-bis(4-nitrophenyl)-[17O]oxirane: (70 mg, 16% yield). 1H
NMR (300 MHz, CDCl3): δ = 8.11 (d, 3JHH = 8.66 Hz, 4H), 7.40 (d,
3JHH = 8.66 Hz, 4H), 4.55 (s, 2H) ppm. 13C NMR (75.4 MHz, CDCl3) δ
= 147.5, 140.7, 127.5, 123.4, 59.0 ppm. 17O NMR (67 MHz, CDCl3) δ =
9 ppm. The level of 17O isotopic enrichment was determined to be
about 9% for both compounds by mass spectrometry performed on a
Micromass GCT (GC-EI TOF Mass Spectrometer) with + polarity.
Details are provided in the Supporting Information.
Synthesis of [Hydroxy(mesyloxy)iodo]benzene.
(Diacetoxy)iodobenzene (1.950 g, 6.0931 mmol) was suspended in
11.25 mL acetonitrile, to which were added methanesulfonic acid
(1.20 g, 12.5 mmol) and water (225 mg, 12.5 mmol) in 2.5 mL
acetonitrile. The mixture was stirred overnight. The off white
powder was then filtered, washed with acetone and ether, and dried
in vacuo. (1.591 g, 82% yield) 1H NMR (300 MHz, DMSO-d6): δ = 9.75
(s, 1H), 8.22 (d, 3JHH = 8.20 Hz, 2H), 7.72 (t, 3JHH = 7.50 Hz,
1H), 7.612 (dd, 3JHH = 8.20, 7.50 Hz, 2H), 2.29 (s, 3H) ppm. 13C
NMR (75.4 MHz, DMSO-d6): δ = 137.57, 131.15, 128.18, 39.96 ppm.
Synthesis of [18O]-Iodosylbenzene. Because 18O-labeled water is
considerably cheaper than 17O-labeled water, we first tested the
synthesis with 18O-labeled water. [Hydroxyl(mesyloxy)iodo]benzene
(350 mg, 1.0937 mmol) was dissolved in H218O (500 mg, 25 mmol)
contained in a centrifuge tube. Sodium hydroxide (50 mg, 1.25 mmol)
was added and the tube was shaken and centrifuged. The liquid layer
was removed and the powder was washed repeatedly with ether and
then water (206 mg, 84% yield). FTIR (powder): 3049 s, 1566 m, 1434
s, 734 s, 689 s, 565 w, 485 m, 424 m cm-1. The observation of IR
bands at 565 and 424 cm-1 confirmed the > 90% 18O isotopic
enrichment in iodosylbenzene.
Synthesis of [17O]-Iodosylbenzene.
[Hydroxyl(mesyloxy)iodo]benzene (350 mg, 1.0937 mmol) was dissolved
in H217O (500 mg, 26.3 mmol) contained in a centrifuge tube. Sodium
hydroxide (50 mg, 1.25 mmol) was added and the tube was shaken and
centrifuged. The liquid layer was removed and the powder was washed
repeatedly with ether and then water. (153 mg, 63% yield). FTIR
(powder): 3049 s, 1566 m, 1434 s, 733 s, 689 s, 587 w, 487 m, 436 m
cm-1.
Synthesis of 2,2,3-Triphenyl-[17O]oxirane: Triphenylethylene
(200 mg, 0.780 mmol) was combined with Jacobsen’s catalyst (50 mg,
0.078 mmol).38 [17O]-iodosylbenzene (172 mg, 0.778 mmol) was added
over two minutes and the solution was refluxed for 7 days.
17O-iodosylbenzene (83 mg, 0.38 mmol) was then added and the
mixture was stirred for three days further. The solvent was removed
in vacuo and the crude product was isolated using a silica column
(mobile phase 10% ethyl acetate: 90% hexanes). The remaining
impurities were dissolved using a minimum of hexanes. (104.8 mg,
49% yield). 1H NMR (300 MHz, CDCl3), δ = 7.37 (m, 6H), 7.24 (m,
3H), 7.18 (m, 3H), 7.08 (m, 3H), 4.37 (s, 1H) ppm. 13C NMR (75.4
MHz, CDCl3), δ = 141.03, 135.83, 135.45, 127.87, 127.82, 127.75,
127.68, 127.60, 127.53, 126.79, 126.37, 68.70, 68.09 ppm. 17O NMR
(67 MHz, CDCl3) δ = 47 ppm.
X-ray crystallography
Among the three oxirane compounds investigated in this study,
only Compound 1 has its crystal structure reported in the
literature.37 We were able to obtain a single crystal of Compound 2
and determine its crystal structure. Attempts to obtain a single
crystal of Compound 3 were unsuccessful. A colorless, rod-like
crystal of Compound 2 having the approximate dimensions of 0.125
0.118 0.075 mm, coated with oil (Paratone 8277, Exxon), was
collected onto the aperture of a mounted MicromountTM (diameter of
the aperture: 100 microns; MiTeGen - Microtechnologies for
Structural Genomics; USA) and quickly transferred to the cold
nitrogen gas stream of the Oxford Cryostream 800 operating at 93.16
°C. The mounted MicromountTM had previously been inserted into a
reusable magnetic goniometer base (B3S-R, MiTeGen -
Microtechnologies for Structural Genomics; USA). All measurements
were made on a Bruker AXS D8 Venture Duo diffractometer using Mo K
radiation ( = 0.71073 Å) generated by a high brilliance Incoatec Is
microfocus tube equipped with a HELIOS multilayer mirror optics
(power: 50 kV 1 mA). Data were recorded with a Bruker AXS PHOTON II
Charge-Integrating Pixel Array Detector (CPAD) (frame size: 768 ×
1024). The structure was solved using direct methods and refined by
full-matrix least-squares method on F2 with SHELXL-2014 using
ShelXle as the graphical user interface.39 Hydrogen atoms of the CH
groups were included at geometrically idealized positions (C-H bond
distances: 0.95 Å) and were not refined. The isotropic thermal
parameters of these hydrogen atoms were fixed at 1.2 times
(CH-groups) that of the preceding carbon atom. The hydrogen atoms
attached to the carbon atoms labeled as C(7) and C(8) were located
in the difference Fourier map. The coordinates and isotropic
parameters for these hydrogen atoms were refined. Data collection
and refinement conditions are listed in Table 1. Other detailed
crystallographic data are given in the Supporting Information.
Solid-state 17O NMR
Solid-state 17O NMR spectra were recorded at 14.1 and 21.1 T,
operating at the 17O Larmor frequencies of 81.38 and 122.02 MHz,
respectively. Experiments performed at 14.1 T utilized a 4 mm
Bruker HX probe and samples were packed into 4 mm o.d. zirconia
rotors. On this probe, the B1 field at the 17O Larmor frequency was
about 50 kHz. All experiments at 21.1 T were performed at the
National Ultrahigh-Field NMR Facility for Solids (Ottawa, Ontario,
Canada) using a home-built solenoid 5 mm HX static probe for static
samples and a 3.2 mm MAS Bruker HX probe for magic angle spinning
(MAS). On both probes, the B1 field at the 17O Larmor frequency was
approximately 42 kHz. For the static experiments, a 5-mm Teflon
tube was used as sample holder. In the MAS experiments, the sample
spinning frequency was 22 kHz. In the 17O MAS experiment for
Compound 3, the sample was cooled to 5 oC using a Bruker BCU05
cooling unit while its MAS spectrum was recorded. NMR spectra were
analysed using Bruker Topspin 2.0. Solid-state 17O NMR spectra were
fitted using DMFit.40
Quantum chemical computations
All property calculations were performed on molecules that were
either optimized using the same method/basis set combination as was
used for the specific property calculation, or were performed on
original crystal structures. All quantum chemical calculations were
carried out using Gaussian 09.41 The licensing for the software
packages is provided by the Center for Advanced Computing (CAC)
(Queen’s University, Kingston, Ontario, Canada). Calculations are
submitted directly to the Frontenac Cluster. Typically, 12
processors were used for each calculation. All optimization and NMR
calculations were performed for gas phase molecules. Structural
optimizations and NMR calculations were performed using
B3LYP/6-311++G(3df,3pd) and the GIAO method. Structural
optimizations and NMR calculations for ethylene oxide and dimethyl
ether were performed using B3LYP/6-311G(d,p) and the GIAO
method.
3. Results and discussion
Crystal structure of Compound 2
In this section, we describe the new crystal structure of
Compound 2. Figure 1 shows the molecular structure of Compound 2.
The geometrical parameters around the central three-membered ring
are: rC7-O1 = 1.435, rC8-O1 = 1.435, rC7-C8 = 1.480 Å, C7-O1-C8 =
62.08. These are very similar to those found in the crystal
structure of the cis isomer:37 rC7-O1 = 1.432, rC8-O1 = 1.441,
rC7-C8 = 1.471 Å, C7-O1-C8 = 61.60. It is also interesting to note
that the two crystal structures are also similar to the geometry of
the parent compound, ethylene oxide (Compound 4), which was
determined by microwave spectroscopy in the gas phase: rCO = 1.434,
rCC = 1.470 Å, ∠COC = 61.67o.42
NMR spectral analysis
Figure 2 shows the solid-state 17O NMR spectra of Compounds 1,
2, and 3 recorded at two magnetic fields, 14.1 and 21.1 T, under
both MAS and static conditions. In general, the major features in
the static 17O NMR spectra for these oxirane compounds are typical
of those arising from the second-order quadrupole interactions.33
This observation immediately suggests that the 17O chemical shift
anisotropy is rather small for these compounds. At 21.1 T, as the
second-order quadrupole broadening is reduced, we were able to
obtain high-quality 17O MAS NMR spectra for these compounds. As
seen from Figure 2, the experimental 17O MAS NMR spectra display
characteristic line shapes suggesting the presence of relatively
large CQ but rather small ηQ values. We should point out that the
spectral quality for Compound 3 is rather low because of the low
17O enrichment level of the product. Nonetheless, all solid-state
17O NMR spectra obtained for Compounds 1-3 can be properly
simulated and the final results for the 17O QC and CS tensors are
listed in Table 2. Some geometric parameters are also given in
Table 2. Among the three oxirane compounds studied (Compounds 1-3),
it appears that changing the regiochemistry and the nature of the
substituents on the oxirane ring does not have a large effect on
its structural features. We also found that Compounds 1-3 display
very similar 17O QC and CS tensors. For example, the CQ(17O) values
in these oxirane compounds are about 12-13 MHz and the asymmetry
parameters are around 0.2. In addition, the 17O CS tensors have
rather small span ( = 11 – 33 ≈ 200-250 ppm). Table 2 also lists
computational results for the 17O QC and CS tensors for Compounds
1-3. In general, the agreement between the experimental and
computed 17O NMR results is reasonably good.
Now we can compare the observed 17O QC and CS tensor data in 1-3
with those previously reported for the R-O-R (R, R = H or C) type
of oxygen atoms. The CQ(17O) values in oxiranes (≈ 13 MHz) are
found to be considerably larger than those in water (H-O-H, CQ ≈
7-10 MHz),43-49 hydroxyl groups (C-O-H, CQ ≈ 9-10 MHz),50-55 and
ethers (C-O-C, CQ ≈ 10-12 MHz),56-57 but still smaller than those
found in the H-O-X type (X = N and O) of bonding (for example, the
hydroxylammonium cation, HONH3+, has CQ(17O) = 14.7 MHz;58 hydrogen
peroxide, HOOH, has CQ(17O) = 16.3 MHz).59 Another distinct feature
of the 17O QC tensors in 1-3 is that the ηQ value is rather small,
ηQ ≈ 0.2. In comparison, all the compounds mentioned above have ηQ
> 0.6. We will further discuss this difference in a later
section. In the literature, there are fewer studies where 17O CS
tensors are reported for the R-O-R (R, R = H or C) type of oxygen
atoms. For the water molecules in crystalline hydrates, the spans
of the 17O CS tensor, , are typically less than 80 ppm.47, 49
Similarly, the value of (17O) in the hydronium ion, H3O+, is also
small, 87 ppm.60 For the C-O-H groups in phenol and hemiketal
compounds, (17O) is typically on the order of 70-90 ppm,52, 54
which is still smaller than those found in Compounds 1-3. It is
interesting to note that the 17O NMR tensor parameters in 1-3 are
somewhat similar to those reported for the ether type O atom in
[5-17O]-D-glucose.61 In general, compounds with high CQ but small
values would benefit the most by going to ultrahigh magnetic fields
such as 35.2 T.62
One of the advantages of the solid-state 17O NMR method employed
in this study is that one can obtain information about tensor
orientation in the molecular frame of reference. Here we will
further examine the 17O QC and CS tensor orientations in oxiranes.
In particular, we are interested in comparing the tensor
orientations in the highly strained geometry of oxiranes (with a
C-O-C angle of 60) with those in a model ether, dimethyl ether (5),
where the C-O-C angle is about 113. The computed 17O NMR tensors
for dimethyl ether are also listed in Table 1. As seen from Figure
3, for oxiranes, the least shielded component, 11, of the 17O CS
tensor lies in the molecular plane bisecting the C-O-C angle and
the most shielded component, 33, is perpendicular to the oxirane
ring. In contrast, for dimethyl ether, 11 lies in the plane but
along the tangent direction of the C-O-C angle and 22 is
perpendicular to the C-O-C plane. Because the 17O chemical shift
anisotropies are rather small in both oxiranes and dimethyl ether,
it is not possible to identify predominant molecular orbital
contributions to individual tensor components. For this reason, we
will not further discuss them. As seen from Figure 3, the 17O QC
tensors of oxirane and dimethyl ether share a common feature in
that both tensors have their largest components, zz, aligning
perpendicular to the molecular plane. Computations also confirm
that the sign of CQ(17O) is positive in both cases; see Table 2.
However, one key difference between the 17O QC tensors in these two
systems is the interchange of orientations of xx and yy. As seen in
Figure 3, in oxiranes, yy bisects the C-O-C angle whereas in
dimethyl ether it is xx. We note that the 17O QC tensor orientation
in dimethyl ether is the same as that observed for the water
molecule.43 The difference in the 17O QC tensor orientations shown
in Figure 3 between dimethyl ether and ethylene oxide is also
related to the fact that oxirane compounds often exhibit ηQ ≈ 0 but
dimethyl ether has ηQ ≈ 1. The distinct 17O QC tensor orientation
in oxiranes (in particular, ethylene oxide) was also noted in
earlier studies by Gready.63-64 In the following section, we will
provide an explanation as to the origin of the different 17O QC
tensors in oxirane and dimethyl ether.
On the basis of the Townes-Dailey model,65 it is
well-established that, for oxygen atoms in the R-O-R type of
bonding geometry, ηQ of the 17O QC tensor depends on the bond
angle, , in the following fashion:66-68
[1]
[2]
Using the above equations, one predicts that ηQ is 0.84 for
dimethyl ether ( = 113), which is in good agreement with the ab
initio computational results shown in Table 2. For ethylene oxide,
although the above equation is not strictly valid (as the three
membered ring has < 90), the observed small ηQ value does
resemble the extreme case of 90 (ηQ = 0). Of course, for the “bent”
bonds, the hybrid atomic orbitals are no longer aligned with the
bond directions. To further understand the 17O QC tensors observed
for dimethyl ether and ethylene oxide, it is important to analyze
the electron lone-pairs around the oxygen atom under study. The
results from a Natural Bonding Orbital (NBO) analysis are shown in
Figure 4. The oxygen atom in each compound has two electron
lone-pairs. The common feature between the two compounds is that
they both have one electron lone-pair, LP(2), with an essentially
full occupancy (1.92 electrons) in the pure pz atomic orbital
pointing in the direction perpendicular to the molecular plane.
Because this direction clearly has an excess of valence p-orbital
populations, it corresponds to the direction along which the
largest 17O QC tensor component lies, as we explained in a recent
study using the concept of valence p-orbital population anisotropy
(VPPA).31 The key difference between the two compounds, however,
lies in the configuration of LP(1). As seen from Figure 4, while
dimethyl ether has its LP(1) in an sp1.39 hybrid orbital (42% 2s
and 58% 2p) pointing along the y-axis, the LP(1) of ethylene oxide
has much less p characters (an sp0.39 hybrid orbital has 72% 2s and
28% 2p). Because of the lack of p-character in LP(1) of ethylene
oxide, the valence p-orbital populations in the px and py orbitals
are primarily from those making the C-O bonds, which are also
mainly pure p atomic orbitals (the hybrid orbital on the oxygen
atom to make the C-O bond has 23% 2s and 87% 2p). As a result, the
valence p-orbital populations in the px and py orbitals are
essentially the same, which leads an approximately axially
symmetric 17O QC tensor in ethylene oxide (i.e., ηQ 0). For
dimethyl ether, on the other hand, because its LP(1) has a
considerable amount of p-character, the valence p-orbital
population in py is significantly greater than that in px,
resulting in a high ηQ value; see data in Table 2.
4. Conclusions
In this study, we have reported synthesis of three 17O-labeled
oxirane compounds. Using solid-state 17O NMR, we were able to
measure the 17O QC and CS tensors in these compounds. During the
course of this study, we have also determined the crystal structure
for (2S*,3R*)-2,3-bis(4-nitrophenyl)oxirane (Compound 2). The 17O
QC tensor in an oxirane molecule typically displays CQ = 12-13 MHz
and ηQ = 0.1-0.2, whereas the 17O CS tensor has a relatively small
anisotropy ( = 200-250 ppm). We found that the oxirane structural
parameters and the 17O NMR tensors are similar in all the three
oxirane compounds examined in this study, despite the differences
in regiochemistry and substituents on the oxirane ring. In general,
oxirane compounds show similar 17O NMR parameters as those of the
R-O-R (R, R = H and C) type of functional groups. However, when
compared with dimethyl ether, oxiranes display distinct 17O QC and
CS tensor orientations as a result from the constrained C-O-C bond
angle. In addition, dimethyl ether and oxirane also represent two
extreme cases of the 17O QC tensor in terms of their asymmetry
parameters (dimethyl ether has ηQ 1, but oxiranes have ηQ 0). In
the field of solid-state 17O NMR for organic and biological
molecules, there are continuing efforts to synthesize new
17O-labeled functional groups and to characterize 17O NMR tensors.
These studies will ultimately lead to understanding of the
relationship between 17O NMR tensors and molecular
structure/chemical bonding.
Acknowledgement
This work was supported by the Natural Sciences and Engineering
Research Council (NSERC) of Canada. A.R. thanks the Government of
Ontario for an Ontario Graduate Scholarship. Access to the 900 MHz
NMR spectrometer was provided by the National Ultrahigh Field NMR
Facility for Solids (Ottawa, Canada), a national research facility
funded by a consortium of Canadian universities, National Research
Council Canada and Bruker BioSpin and managed by the University of
Ottawa (http://nmr900.ca).
Supporting Information Available. MS data analysis for Compounds
1 and 2. Detailed crystallographic data for Compound 2. A
crystallographic information file (CIF) for Compound 2 has been
deposited to the Cambridge Crystallographic Data Centre
(CCDC-1997472).
Tables and Figure Captions
Table 1. Crystallographic data for (2S*,
3R*)-2,3-bis(4-nitrophenyl)oxirane (Compound 2).
Table 2. Experimental and computed (G09) 17O NMR parameters and
selected structural parameters for Compounds 1, 2, and 3, ethylene
oxide (4), and dimethyl ether (5). The uncertainties in the
experimental 17O CS tensor components were estimated to be 10 ppm
by visual inspection of the agreement between experimental and
simulated spectra.
Compd
δiso (ppm)
δ11 (ppm)
δ22 (ppm)
δ33 (ppm)
CQ (MHz)
ηQ
∠COC (o)
rCO (Å)
1
Exp.
30 2
160
–15
–55
12.1 0.2
0.18 0.10
61.60a
1.436a
Cal.
30
193
–33
–70
13.4
0.22
61.59b
1.432b
2
Exp.
30 2
180
–33
–70
13.4 0.2
0.22 0.10
62.09b
1.435b
Cal.
31
171
4
–81
13.3
0.22
62.97b
1.428b
3
Exp.
43 2
173
–9
–35
12.8 0.2
0.20 0.10
Cal.
42
183
–13
–44
12.9
0.17
63.14b
1.424b
4
Exp.
12.6c
0.17c
61.67d
1.434d
Cal.
–11
176
–52
–157
14.1
0.28
59.46b
1.490b
5
Cal.
–16
7
–5
–49
12.3
0.90
113.0b
1.450b
aFrom ref. 37. bThis work. cFrom ref. 22. dFrom ref. 42.
Figure 1. Crystal structure of Compound 2. Thermal ellipsoids
are shown at the 30% probability level.
Figure 2. Experimental (blue trace) and simulated (red trace)
17O solid-state NMR spectra of (a) 1, (b) 2, and (c) 3. The peak
marked by * was due to the ZrO2 rotor used in MAS experiments. The
sample spinning frequency was 22 kHz. All spectra were recorded
with a Hahn-echo pulse sequence with central-transition selective
pulses and a recycle delay of 10 s. Other data acquisition
parameters are given below. In (a), 8000 transients for the MAS at
21.1 T; 13000 transients for the static experiment at 21.1 T; 41432
transients in the static experiment at 14.1 T. In (b), 24000
transients for the MAS at 21.1 T; 14000 transients for the static
experiment at 21.1 T; 17262 transients in the static experiment at
14.1 T. In (c), 33000 transients for the MAS at 21.1 T; 16000
transients for the static experiment at 21.1 T; 21960 transients in
the static experiment at 14.1 T.
Figure 3. Depiction of the 17O CS (a and c) and QC (b and d)
tensor orientations in the molecular frames of reference of oxirane
(a and b) and dimethyl ether (c and d). Tensor components that are
perpendicular to the paper plane are not shown for clarity.
Figure 4. NBO results on electron lone-pairs in (a) dimethyl
ether and (b) ethylene oxide.
TOC graphics
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2
1
* *
δ(17O)/ppm -1000 0
δ(17O)/ppm -1000 -500 0 500 1000
(a)
0 500 -500 -1000 1000 δ(17O)/ppm
* *
1000 500 -500
(b) (c)
MAS at 21.1 T
Static at 21.1 T
Static at 14.1 T
*
*
*
δ(
17
O)/ppm
-1000 0
δ(
17
O)/ppm
-1000
-500
0
500
1000
(a)
0 500 -500 -1000 1000
δ(
17
O)/ppm
*
*
1000 500 -500
(b) (c)
MAS
at 21.1 T
Static
at 21.1 T
Static
at 14.1 T
*
δ11
δ22 χxx
χyy (a) (b)
(c) (d)
113° 113°
δ11
δ33
χyy
χxx
60° 60°
δ
11
δ
22
χ
xx
χ
yy
(a) (b)
(c) (d)
113° 113°
δ
11
δ
33
χ
yy
χ
xx
60° 60°
(a) (b)
O
y
x
LP(1): spy0.39 LP(2): pz
O
y
x
LP(1): spy1.39 LP(2): pz
113° 60°
(a) (b)
O
y
x
LP(1): sp
y
0.39
LP(2): p
z
O
y
x
LP(1): sp
y
1.39
LP(2): p
z
113° 60°
17
O NMR
O
C C
~ 60
o
1
2
3
