Real-time mechanistic monitoring of an acetal hydrolysis using ultrafast 2D NMR

Article abstract of DOI:10.1002/mrc.3827

Ultrafast (UF) 2D NMR makes it possible to obtain a 2D NMR spectrum in less than a second. Here, UF-HSQC experiments are used for the real-time mechanistic study of an acetal hydrolysis at 13C natural abundance, and it is possible to characterize the presence of the hemiacetal, an intermediate with a well-known short lifetime. The assignments are confirmed and rationalized by quantum calculations of 1H and 13C NMR chemical shifts and natural bonding orbital analysis. Copyright

Full text of DOI:10.1002/mrc.3827

Research Article
Received: 17 February 2012
Revised: 4 April 2012
Accepted: 22 April 2012
Published online in Wiley Online Library: 21 May 2012
(wileyonlinelibrary.com) DOI 10.1002/mrc.3827
Real-time mechanistic monitoring of an acetal
hydrolysis using ultrafast 2D NMR
Luiz H. K. Queiroz Jr.,a,b* Patrick Giraudeau,c Fabiane A. B. dos Santos,a
Kleber T. de Oliveiraa and Antonio G. Ferreiraa
Ultrafast (UF) 2D NMR makes it possible to obtain a 2D NMR spectrum in less than a second. Here, UF-HSQC experiments are used
for the real-time mechanistic study of an acetal hydrolysis at ¹³C natural abundance, and it is possible to characterize the presence
of the hemiacetal, an intermediate with a well-known short lifetime. The assignments are confirmed and rationalized by quantum
calculations of ¹H and ¹³C NMR chemical shifts and natural bonding orbital analysis. Copyright © 2012 John Wiley & Sons, Ltd.
1
Keywords: NMR; H; 13C; ultrafast NMR; NMR theoretical calculations; acetal hydrolysis; hemiacetal intermediate
also allows the characterization of the short lifetime hemiacetal
intermediate. Experimental results are confirmed by theoretical
Introduction
Multi-dimensional NMR experiments form a powerful tool for a
variety of applications, from structural elucidation of organic
compounds to the determination of biomolecular structures.
However, it requires hundreds of transients to complete the
acquisition of the data, which leads to a long experiment duration
(up to several hours).[1,2] Because of this time constraint, 2D NMR is
ill-suited for studying dynamic phenomena occurring on a short
time scale, such as chemical exchange, protein folding or more
generally kinetics of fast chemical reactions. Many strategies have
been described to overcome this time constraint and to obtain
nD NMR spectra in a shorter time.[3–5] One of the most efficient
approaches in reducing the experiment time is the so-called
‘ultrafast NMR’ (UF-NMR) methodology, based on the spatial
encoding of NMR interactions.[6,7] Recent years have witnessed
numerous methodological developments,[8,9] which improved
the performances of ultrafast NMR, thus making possible to
perform, in principle, any kind of multidimensional NMR
experiment in a single scan.
The advent of UF-NMR opens the way to new applications in
chemistry, including the real-time monitoring of short time scale
phenomena.[10] Recently, the application of TOCSY, HSQC and
HMBC UF-NMR experiments was reported for the mechanistic
study of a specific organic reaction, making possible to detect
different intermediate species.[11–13] UF-NMR is emerging as a
potential technique to study mechanisms in organic reactions
at natural abundance.
calculations of NMR chemical shifts and natural bond orbital
(NBO) analysis.
Methods and Materials
Synthesis of 2-(4-nitrophenyl)-1,3-dioxolane[16]
4-Nitrobenzaldehyde (12.20 g, 80.73 mmol) and p-toluenesulfonic
acid monohydrate (306 mg, 1.61 mmol) were dissolved in toluene
(150 mL). Ethylene glycol (10 mL, 180.8 mmol) was added, and
the solution was refluxed for 3 h with a Dean-Stark trap, to
remove the water. After that, the solution was allowed to cool,
and 200 mL of AcOEt were added. The organic layer was washed
with saturated NaHCO3 solution (2 ꢀ 100 mL) and then washed
with saturated NaCl solution (100 mL). The organic layer was dried
with MgSO4 and the solvent was removed under reduced pressure
to give the desired protected aldehyde. (15.57 g, 99% yield). mp =
92–93 ꢁC. 1 H-NMR (CDCl3, 400 MHz), d ppm: 4.06-4.16 (m, 4 H);
5.90 (s,1 H); 7.66 (d, 2 H, J = 8.5 Hz); 8.24 (d, 2 H, J = 8.5 Hz).13 C-NMR
(CDCl3, 100 MHz), d (ppm): 148.4 (C); 145.0 (C); 127.4 (2 ꢀ CH);
123.6 (2 ꢀ CH); 102.3 (CH); 65.5 (2 ꢀ CH2). m/z: 195 [M].+,194,
148, 107, 77, 73.
Acetals are a very important class of organic compounds and
are normally hydrolyzed using water and an acid catalyst.[14] How-
ever, identifying the intermediates of these hydrolysis reactions is
problematical because the lifetime of these species are very short.
A recent work reported an unsuccessful attempt to identify the
hemiacetal intermediate, in an acetal hydrolysis reaction using
water and an acid catalyst, by 1H NMR experiments.[15]
This paper presents the real-time monitoring of an acid-
catalyzed acetal hydrolysis reaction by UF-HSQC experiments,
with no need for 13C-labeling. Although this work shows the
potentialities of UF-NMR for real-time mechanistic studies, it
*
Correspondence to: Luiz H. K. Queiroz Jr., Laboratório de Ressonância Magnética
Nuclear, Departamento de Química, Universidade Federal de São Carlos (UFSCar),
Rod. Washington Luís, Km 235, C.P. 676, CEP 13565-905, São Carlos, SP, Brazil.
E-mail: professorkeng@gmail.com
a Laboratório de Ressonância Magnética Nuclear, Departamento de Química,
Universidade Federal de São Carlos (UFSCar), São Carlos, SP, Brazil
b Laboratório de Ressonância Magnética Nuclear, Instituto de Química,
Universidade Federal de Goias, Goiânia, GO, Brazil
c
Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse,
Modélisation (CEISAM) UMR 6230, Nantes, France
Magn. Reson. Chem. 2012, 50, 496–501
Copyright © 2012 John Wiley & Sons, Ltd.

Real-time mechanistic monitoring of an acetal hydrolysis using ultrafast 2D NMR
Ultrafast 2D HSQC
The UF-HSQC pulse sequence employed for this study is
presented in Fig. 2. It was described in several recent
papers,[8,22] and its efficiency for monitoring chemical reactions
was recently shown on a model example.[23]
All the UF-HSQC spectra were obtained at 298 K on a Bruker
Avance III spectrometer operating at 400.15 MHz 1 H frequency,
with a BBI 5 mm probe with z-axis gradients of 50 G/cm
maximum amplitude. For the encoding block, two 15 ms chirp
pulses were applied simultaneously with ꢂ15 G/cm encoding
gradients inducing a frequency dispersion much larger than the
13 C frequency range. The amplitude of gradients G1 and G2
(ꢃ35 G/cm and ꢃ14.3 G/cm, respectively) were optimized to fold
resonances in the spatially encoded dimension.[8] Acquisition
gradient parameters were set as follows: Ga = 35 G/cm, Ta = 256
ms, 128 detection gradient pairs. For the INEPT block, the delay
was 1.72 ms (corresponding to an average 1JCH coupling constant
of 145 Hz), and for each spectrum, eight scans were performed.
For the processing of the UF spectra, a home-written routine
in TopSpinW was applied, including an optimized apodization
in the spatially encoded dimension to improve lineshape and
sensitivity,[9] a p/8 shifted sine apodization in the conventional
(Echo-Planar-Imaging) dimension, zero-filling procedures in both
dimensions and processing of all the spectra in magnitude mode.
This pulse sequence includes several of the recent improve-
ments brought to ultrafast NMR, including optimized spatial-
encoding parameters to obtain the best compromise between
sensitivity and resolution. Folding gradients were implemented
to increase the accessible spectral width.[8] Moreover, gradient-
based coherence selection and phase cycling efficiently remove
the signal arising from 1 H bound to 12 C, making it possible to
work at natural 13 C abundance. Finally, a two-pulse spatial
encoding was chosen as recently described.[8,22,23] Although a
multi-echo spatial encoding can be useful to limit sensitivity
losses because of translational diffusion,[24] these effects are less
important in the case of 13 C, and no significant improvement
was obtained when trying the multi-echo encoding scheme in
this study.
After acquiring an initial spectrum of the acetal, the NMR tube
was taken out, and the TFA was added (at t = 0). Then, the tube
was put back in the spectrometer. The evolution of the reaction
was monitored by continuous acquisition of UF-HSQC spectra
every 41 s. This time corresponds to a eight-scan experiment,
which was necessary for sensitivity and phase-cycling purposes.
We initially tried to preserve the ‘ultrafast’ nature of the
experiments by recording single-scan signals and fitting the
time evolution, in analogy to 2D FT NMR, where even if each
transient does not have enough signal to noise the Fourier
transform might lead to observable signal. This solution would
have increased the temporal resolution; however, the sensitivity
losses were too high to observe the less intense peaks.
Therefore, eight scans were found to be the best compromise
between sensitivity and temporal resolution.
Theoretical calculations
For the theoretical calculations of the acetal, intermediate and
final product of the hydrolysis reaction, the input files were
prepared for the three compounds, and all the calculations were
carried out through GAUSSIAN 03.[17] The structures were
optimized using the MP2 method[18] and the basis set cc-
pVDZ,[19,20] including the solvent effect, chloroform, by polarizable
continuum model (PCM) model.[21] The NBO analysis was
performed with optimized structures with MP2 method and
cc-pVTZ basis set.
The calculations of NMR shielding tensors also take into
account the optimized structures and were performed through
the GIAO method with B3LYP theory level and cc-pVTZ. The
effect of the solvent was included in this calculation by the
same way as for the optimization. The shielding tensors were
converted in chemical shifts (d) taking as reference the 1 H and
13 C shielding tensors of tetramethylsilane in the level of theory.
The most representative UF-HSQC spectra acquired in the course
of the hydrolysis reaction are presented in Fig. 3. Representative
cross-sections are also shown in Fig. 4. The spectrum acquired at
0.00 min shows the correlation of the acetal protected carbon
(C-2), whereas the two other peaks, which are folded into the
observed spectral window, correspond to the aromatic CHs
(C-7,11 and C-8,10). After 1.15 min, it is possible to observe a new
correlation highlighted by a red arrow, which is not present on
the spectrum acquired at 36.42 min but reappears at 38.47 min
and continues to rise and fall during the reaction. This correla-
tion was assigned to the protected carbon of the hemiacetal
intermediate 2. The aromatic correlations arising from the
intermediate 2 appear at the same position as those of the
hemiacetal 1. These results are further confirmed by the theoretical
calculations described below.
The formation of the product 3 can be observed on the
spectrum acquired at 87.29 min with the rising of the two
aromatic correlations highlighted in green and folded in the
13 C dimension. The spectrum recorded in the instant 87.29 min
provides important information, as it includes the reactant,
intermediate and product correlations in the same spectrum.
The apparent end of the reaction occurred at 118.50 min, as
verified in the corresponding spectrum where only product 3
correlations could be observed. After this instant, other spectra
were recorded, and all of them showed the same correlations
as those observed at 118.50 min.
Results and Discussion
The reaction chosen for this study is presented in Fig. 1. It
consists in the hydrolysis of the 2-(4-nitrophenyl)-1,3-dioxolane
acetal reacting with trifluoroacetic acid (TFA) in the presence of
residual water from the solvent (deuterated chloroform). The
acetal 1 was synthesized according to the literature.[16] This
reaction was carried out in a 5-mm NMR tube placed in a 400-MHz
spectrometer equipped with a 5-mm BBI probe.
To follow the signal temporal evolution in a more quantitative
manner, we plotted the peak amplitudes as a function of time (Fig. 5).
Although the amplitudes do not directly reflect concentrations,
Figure 1. Reactional scheme of the acid catalyzed hydrolysis reaction of
the 2-(4-nitrophenyl)-1,3-dioxolane acetal.
Magn. Reson. Chem. 2012, 50, 496–501
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L. H. K. Queiroz et al.
Figure 2. Ultrafast HSQC 2D sequence used to monitor the hydrolysis reaction. This sequence includes p-pulses for 13 C decoupling during the acquisition.
Figure 3. A set of 6 UF-HSQC spectra acquired with the pulse sequence of Fig. 2, recorded in the course of the acetal hydrolysis reaction, where the
resonances corresponding to the reactant 1, intermediate 2 and product 3 are highlighted. The CH2 resonances from the acetal and intermediate are
not observed in the accessible spectral width. Aromatic resonances are folded in both dimensions; their actual 13 C and 1 H chemical shifts are indicated
next to the corresponding peak. The aromatic correlations of intermediate 2 are overlapped with those of the acetal 1.
they give an idea of their temporal evolution. As expected, the
acetal peak amplitudes are decreasing regularly in the course of
time, whereas those of the product are increasing. The latter,
however, are observed only from t = 22min, as they are below
the noise level before this time. The most interesting information
obtained from Fig. 5 is the evolution of the intermediate peak
amplitude, which exhibits an unstable but regular evolution. It
shows that the concentration of the intermediate oscillates at a ca.
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Magn. Reson. Chem. 2012, 50, 496–501

Real-time mechanistic monitoring of an acetal hydrolysis using ultrafast 2D NMR
Figure 4. 1H and 13 C cross-sections extracted from Fig. 3 spectra, for the ‘a’ peak of the acetal.
which we could not observe by 1D NMR despite numerous
attempts, probably because of the very short lifetime of this
intermediate. These results open perspectives for the monitoring
of fast organic reactions; however, potential users should keep in
mind that the ultrafast approach is limited by its relatively low
sensitivity. Although the SNR can be increased by signal accumula-
tion – a ‘multi-scan single shot’ approach[25] that we recently
described – this strategy is detrimental to the temporal resolution.
As an example, on the spectrum recorded at 87.29 min in Fig. 3,
the SNR in the 13 C dimension was 7 for peak ‘d’ and 10 for peak
‘a’, whereas it was 5 for peak ‘d’ and 8 for peak ‘a’ in the 1 H dimen-
sion. These values are not far above the limit of detection, which
means that the concentration used in this study (0.44 mol/L) is
probably close to the minimum value that can be used for the
parameters and hardware employed here. However, this experi-
ment was performed at a relatively low field and with a standard
probe; therefore, we expect that the limit of detection could be
decreased by working at higher fields and/or with a cryoprobe.
Moreover, a gain in sensitivity can also be expected from the use
of sensitivity-enhanced schemes.[26]
Figure 5. Amplitude of the 2D peaks (arbitrary units) extracted from the
174 ultrafast 2D spectra recorded in the course of the acetal hydrolysis
reaction. Curve labels refer to the peaks of Fig. 3.
4.8 min rate. The apparent unstable character of the intermediate
appears similar to other intermediates described in a recent work.[12]
It probably explains why previous attempt to detect this intermediate
by conventional NMR methods was unsuccessful.[15]
The results presented in Figs 3–5 highlight the capacity of
UF-NMR to follow chemical reactions in real time. Particularly
interesting is the observation of the signal from the intermediate,
To evaluate the viability of our experimental NMR results, we
completed this experimental study by theoretical investigations.
Nowadays, the quantum calculations of NMR properties are a very
important tool applied in many spectroscopic studies.[27,28] To
confirm the previous experimental assignment of the intermediate
correlation, the shielding NMR tensors (1 H and 13 C chemical shifts)
Magn. Reson. Chem. 2012, 50, 496–501
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L. H. K. Queiroz et al.
of the compounds 1, 2 and 3 were calculated to determine
if the theoretical calculations would indicate a shielding or
deshielding of the 1 H and 13 C NMR signals of the hemiacetal
(2) protected carbon.
As the electron density along this bonding in the hemiacetal 2 is
higher, the resonance frequencies values of the 1 H and 13 C nuclei
are lower in respect to the acetal 1. Thus, the hyperconjugation
effect measured by NBO calculations could explain the shielding
of the NMR signals for the hemiacetal 2. Another important infor-
mation obtained by the NBO analysis is that no NBO interaction
was found between the lone pairs of the oxygens directly bonded
to the protected carbon and the C-H aromatics. This evidence
justifies why the aromatic correlations of the intermediate 2 are
overlapped with the corresponding peaks of the acetal 1.
The calculations were initially performed for the acetal 1 and
product 3 to check if these results would corroborate with the
experimental data for both compounds, what would secure a
degree of reliability to the theoretical calculations for the
hemiacetal 2, whose experimental data were not available.
Optimizations and NBO analysis were performed by using
MP2/cc-pVDZ, and the chemical shifts were evaluated by
using B3LYP/cc-pVTZ.[19,20] All of these NMR calculations included
the solvent effect, which, in this case, was the chloroform.
A good correlation was found between the experimental and
theoretical data for the acetal 1 and the product 3, and the linear
correlation coefficients (R) calculated for both compounds were
higher than 0.99, thus showing an excellent corroboration of
the data. From these good results, the NMR calculations for the
hemiacetal 2 were performed in the same conditions as for
compounds 1 and 3. As previously discussed, the red highlighted
correlation of the intermediate 2 in Fig. 3 showed a 1 H shielding
of 0.79 ppm and a 13 C shielding of 8.5 ppm, in respect to the
acetal 1 correlation. The shielding values obtained by calculation
are 0.69 and 9.1 ppm for 1 H and 13 C, respectively. These values
are in very good agreement with those obtained experimentally,
thus confirming the reliability of the ‘red’ correlation in Fig. 3
attributed to the protected carbon of the short lifetime hemiacetal
intermediate 2.
A point worth dwelling upon is the reason which could explain
why the shielding occurs for both 1 H and 13 C in the hemiacetal 2.
Many studies[29–31] reported that some changes in the chemical
shift or even in the coupling constant values are because of
hyperconjugation effects.
Therefore, the calculation of the NBO for the compounds 1 and
2 was carried out to estimate the hyperconjugation effects in
these molecules. The NBO interactions between the lone pairs
of the oxygens directly bonded to the protected carbon and the
sigma antibonding orbital (s*) C2-H2. The interaction energies
are summarized in Table 1.
Conclusion
The experimental and theoretical results presented above allow
the investigation of the acetal hydrolysis reaction mechanism
and the characterization of a short lifetime hemiacetal interme-
diate 2 that could not be detected by conventional NMR.[15]
Although the hydrolysis of acetals is well known in organic
chemistry, the novelty brought by this study is the detection
and the characterization of the short lifetime intermediate. The
results obtained by ultrafast NMR show the unstable behavior of
the intermediate, thus highlighting the potential of UF NMR
for the investigation of organic species with short lifetimes. In
mechanistic approaches, chemists rarely provide the unequivocal
structure of a reaction intermediate. Now, there is an opportunity
to investigate chemical reactions in solution, using real-time
monitoring and with the complete assignment of the intermediate.
The results obtained with ultrafast NMR reinforce the potentialities
of this methodology for mechanistic studies at 13 C natural
abundance, thus opening interesting perspectives for studying
organic reactions with unknown mechanisms.
To further assess the robustness of the methodology described
in this paper, we are currently studying organic mechanisms
involving acetals, spiroacetals and similar molecules under various
experimental conditions to try to detect the corresponding
intermediates and infer about the kinetic of these reactions.
Acknowledgements
The data showed in Table 1 indicate that the total interaction
energy of NBOs in the hemiacetal 2 is 3.89 kcal higher than that
for the acetal 1. The interaction energy between occupied and
unoccupied orbitals indicates the electron flux from a part of
the molecule to another. The higher is this interaction energy,
the higher is the electron density over the bonding that receives
this flux, thus decreasing the resonance frequency of the
corresponding nuclei. Then, the higher NBO interaction energy in
the hemiacetal 2 increases the electron density along the C2-H2
bonding for this compound when compared with the acetal 1.
P. G. acknowledges funding from the ‘Agence Nationale de la
Recherche’ (ANR Grant 2010-JCJC- 0804–01). L. H. K. Q. Jr., A. G.
F., F. A. B. S. and K. T. O. acknowledge the Coordenação de
Aperfeiçoamento de Pessoal de Nível Superior (CAPES), the
Conselho Nacional de Desenvolvimento Científico e Tecnológico
(CNPq) and the Fundação de Amparo à Pesquisa do Estado de
São Paulo (FAPESP) for the financial support.
References
[1] J. Jeener, Lecture Presented at Ampere International Summer
School, Basko Polje, Yugoslavia, 1971.
[2] W. P. Aue, E. Bartholdi, R. R. Ernst. J. Chem. Phys. 1976, 64,
2229–2246.
Table 1. Natural bond orbital interaction energy (kcal/mol) for the
acetal and hemiacetal.
ꢀ
[3] E. Kupce, R. Freeman. J. Am. Chem. Soc. 2004, 126, 6429–6440.
[4] P. Schanda, B. Brutscher. J. Am. Chem. Soc. 2005, 127, 8014–8015.
[5] B. Vitorge, G. Bodenhausen, P. Pelupessy. J. Magn. Reson. 2010, 207,
149–152.
[6] L. Frydman, T. Scherf, A. Lupulescu. Proc. Natl. Acad. Sci. 2002, 99,
15858–15862.
[7] A. Tal, L. Frydman. Prog. Nucl. Magn. Reson. Spectrosc. 2010, 57,
241–292.
[8] P. Giraudeau, S. Akoka. J. Magn. Reson. 2010, 205, 171–176.
[9] P. Giraudeau, S. Akoka. Magn. Reson. Chem. 2011, 49, 307–313.
[10] M. Gal, M. Mishkovsky, L. Frydman. J. Am. Chem. Soc. 2006,
128, 951–956.
Interaction
Acetal
Hemiacetal
LP1
LP2
LP1
LP2
! s*C(2) – H(2)
1.84
1.41
1.87
0.65
5.77
4.34
3.27
2.05
—
O(1)
O(1)
O(3)
O(3)
! s*C(2) – H(2)
! s*C(2) – H(2)
! s*C(2) – H(2)
Total
9.66
LP1 – Lone Pair 1; LP2 – Lone Pair 2.
wileyonlinelibrary.com/journal/mrc
Copyright © 2012 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2012, 50, 496–501

Real-time mechanistic monitoring of an acetal hydrolysis using ultrafast 2D NMR
[11] A. Herrera, E. Fernández-Valle, R. Martínez-Álvarez, D.
Molero, Z. D. Pardo, E. Sáez. Angew. Chem. Int. Ed. 2009,
48, 6274–6277.
[12] A. Herrera, E. Fernández-Valle, E. M. Gutiérrez, R. Martínez-Álvarez,
D. Molero, Z. D. Pardo, E. Sáez. Org. Lett. 2010, 12, 144–147.
[13] Z. D. Pardo, G. L. Olsen, M. E. Fernández-Valle, L. Frydman, R.
Martínez-Álvarez, A. F. Herrera. J. Am. Chem. Soc. 2012, 134,
2706–2715.
[14] E. H. Cordes, H. G. Bull. Chem. Rev. 1974, 74, 581–603.
[15] W. Li, L. Jianchang, W. Yuchuan, N. Fuller, M. A. Markus. J. Org. Chem.
2010, 75, 1077–1086.
[16] R. J. Briggs, J. Klosin, G. T. Whiteker. Org. Lett. 2005, 7,
4795–4798.
[17] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, J. A. Montgomery Jr, T. Vreven, K. N. Kudin,
J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone,
B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson,
H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li,
J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,
C. Pomelli, J. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth,
P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich,
A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K.
Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford,
J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi,
R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng,
A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. G. Johnson,
W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople. Gaussian 03,
Gaussian, Inc., Wallingford CT, 2004.
[18] C. Møller, M. S. Plesset. Phys. Rev. 1934, 46, 618–622.
[19] T. H. Dunning Jr., J. Chem. Phys. 1989, 90, 1007–1023.
[20] A. K. Wilson, T. van Mourik, T. H. Dunning Jr., J. Mol. Struct. (THEOCHEM)
1995, 388, 339–349.
[21] S. Miertus, E. Scrocco, J. Tomasi. Chem. Phys. 1981, 55, 117–129.
[22] M. Gal, L. Frydman, in Multidimensional NMR Methods for the
Solution State (Eds: G. A. Morris, J. W. Emsley), Wiley, Chichester,
2010, pp. 43–60.
[23] P. Giraudeau, P. Lemeunier, M. Coutand, J.-M. Doux, A. Gilbert,
G. Remaud, S. Akoka. J. Spectrosc. Dyn. 2011, 1, 2–8.
[24] P. Giraudeau, S. Akoka. J. Magn. Reson. 2008, 190, 339–345.
[25] M. Pathan, S. Akoka, I. Tea, B. Charrier, P. Giraudeau. Analyst 2011,
136, 3157–3163.
[26] P. Pelupessy. J. Am. Chem. Soc. 2003, 125, 12345–12350.
[27] J. D. Vilcachagua, L. C. Ducati, R. Rittner, R. H. Contreras, C. F.
Tormena. J. Phys. Chem. A 2011, 115, 1272–1279.
[28] L. H. K. Queiroz Jr., V. Lacerda Jr., R. B. dos Santos, S. J. Greco, A.
Cunha Neto, E. V. R. De Castro. Magn. Reson. Chem. 2011, 49,
140–146.
[29] C. F. Tormena, L. C. Dias, R. Rittner. J. Phys. Chem. A 2005, 109,
6077–6082.
[30] R. H. Contreras, A. L. Esteban, E. Diez, E. W. Della, I. J.
Lochert, F. P. Santos, C. F. Tormena. J. Phys. Chem. A 2006,
110, 4266–4275.
[31] L. C. Ducati, M. P. Freitas, C. F. Tormena. J. Mol. Struct. (THEOCHEM)
2008, 851, 147–157.
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