Tunable conformation and stability of amidourea-based hydrogen-bonded heteroduplexes

Article abstract of DOI:10.1016/j.tet.2012.08.092

A class of multiply hydrogen-bonded heteroduplexes were constructed from readily available amidourea derivatives, and their structures and association stabilities were investigated. Although the amidourea derivatives possessed different spacers or termini, they could adjust their conformations to achieve an optimal binding module. Consequently, all the heteroduplexes adopted similar hydrogen-bonding patterns through eight intermolecular bifurcated hydrogen bonds based on the amidourea motif. Moreover, it was also found that the association stabilities of the heteroduplexes could be well tuned by varying the spacers or termini of the monomers.

Full text of DOI:10.1016/j.tet.2012.08.092

Tetrahedron 68 (2012) 9200e9205
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Tunable conformation and stability of amidourea-based hydrogen-bonded
heteroduplexes
*
Wei-Jun Chu, Chuan-Feng Chen
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences,
Beijing 100190, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 July 2012
Received in revised form 22 August 2012
Accepted 28 August 2012
Available online 3 September 2012
A class of multiply hydrogen-bonded heteroduplexes were constructed from readily available amidourea
derivatives, and their structures and association stabilities were investigated. Although the amidourea
derivatives possessed different spacers or termini, they could adjust their conformations to achieve an
optimal binding module. Consequently, all the heteroduplexes adopted similar hydrogen-bonding pat-
terns through eight intermolecular bifurcated hydrogen bonds based on the amidourea motif. Moreover,
it was also found that the association stabilities of the heteroduplexes could be well tuned by varying the
spacers or termini of the monomers.
Keywords:
Amidourea
Hydrogen bond
Heteroduplex
Conformation
Stability
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
heterocycle modules, various hydrogen-bonding motifs were
designed. For instance, Gong et al.9 designed a system of aromatic
Due to its high strength, specificity, directionality, cooperativity,
and reversibility, multiple hydrogen-bond-mediated self-assembly
is not only the cornerstone of biological systems, but also has
widespread applications in supramolecular chemistry and mate-
rials science.1 Molecular duplexes are a main kind of multiple
hydrogen-bond-mediated self-assemblies. In particular, the
double-helical structure of DNA2 via hydrogen bonds, hydrophobic
oligoamide duplexes, the stability of which is directly proportional
to its number of interstrand hydrogen bonds. Li et al.10 and our
group11 developed hydrogen-bonded duplexes based on the hy-
drazide motif. Recently, we constructed a class of amidourea-based
homoduplexes,12 which showed high stability, and a class of
amidourea-based heteroduplexes,13 which revealed assembling
selectivity.
effects, and
p
e
p
stacking interactions as genetic information car-
Considering their widespread applications, the number of
multiple hydrogen-bonding modules available for use is still lim-
ited. Therefore, it is highly desirable to develop new hydrogen-
bonded duplexes with ready synthetic accessibility, and high and
tunable association stability. The association stability is the major
parameter of multiple hydrogen-bonding duplexes, which largely
determines their usefulness. The stability is affected by many fac-
tors, including the species and number of individual hydrogen
bonds, the acidity or basicity of hydrogen-bond donors or accep-
tors, the secondary electrostatic interactions between adjacent
hydrogen bonds,14 the tautomeric or conformational preferences of
the monomer,15 the preorganization of the monomer,16 the sub-
stituent effects17 and the solvent polarity. Continuing our previous
work, we herein report a class of multiply hydrogen-bonded het-
eroduplexes based on the amidourea motif. In this system, the as-
sociation stability of the heteroduplexes is well tuned by the
spacers and termini, while maintaining the same sequence of
hydrogen-bond donors and acceptors (Fig. 1).
rier has laid the foundation for modern molecular biology.3
Inspired by the elegant structure and function of DNA, there has
been currently intensive interest in artificial construction of stable
molecular duplexes from unnatural backbones for biomolecule
mimicking and potential applications.4 Different kinds of
hydrogen-bonded duplexes with arrays of hydrogen-bond donors
(D) and acceptors (A) have been developed so far. Among them,
Meijer’s ureidopyrimidone5 and Zimmerman’s ureidodeazapterin6
modules have gained great success, due to their high association
stability and synthetic accessibility.7 Another successful example is
an AAAAeDDDD quadruple hydrogen-bonding duplex that exhibits
extremely strong binding affinity lately reported by Leigh et al.8
To address the tautomeric problem often accompanied with
* Corresponding author. E-mail address: cchen@iccas.ac.cn (C.-F. Chen).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.092

W.-J. Chu, C.-F. Chen / Tetrahedron 68 (2012) 9200e9205
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I
II
Fig. 1. The designed binding motif of the amidourea-based hydrogen-bonded heteroduplexes.
2. Results and discussion
2.1. Design and synthesis
B1 was very weak.13 Herein when the self-assembly property of B2
was examined by 1H NMR dilution study (Fig. 3), no significant
chemical shift changes were observed for all the NH protons, in-
dicating that the self-association of B2 was also weak in CDCl3.
Similarly, 1H NMR dilution studies upon B3 and B4 afforded the
same information, which also suggested the very weak self-
association of B3.
The design of the amidourea-based heteroduplexes has been
demonstrated by the formation of heteroduplex A1$B1.13 The
complexation between DDAADD-sequenced monomers A1, A2 and
ADDDDA-sequenced monomers B2eB4 was then investigated, re-
spectively. When 1H NMR studies were performed on 1:1 mixture
of A1 and B2 (each at 5.0 mM) in CDCl3, all the NH proton signals of
A1 and B2 shifted downfield substantially (Fig. 4), suggesting the
formation of heteroduplex A1$B2. 1H NMR studies on 1:1 mixture
of A2 and B2 (Fig. 4) also indicated that heteroduplex A2$B2 was
formed. The structures of these heteroduplexes were investigated
by the density functional theory (DFT) calculation at the B3LYP/6-
31þG(d,p) level, which revealed that they possessed almost the
same hydrogen-bonding pattern based on the amidourea motif
(Fig. 5), although monomers A1 and A2 had different spacers. In
order to achieve an optimal binding module, B2 adopted a much
more bending conformation in heteroduplex A1$B2 than that in
heteroduplex A2$B2, whereas the rigid A1 and A2 both existed in
nearly planar conformations. Unequivocal evidences for the for-
The assembling strategy for the multiply hydrogen-bonded
heteroduplexes involves the combination of two series of readily
available amidourea derivatives I and II, which are expected to give
rise to the complementary DDAADD and ADDDDA hydrogen-
bonding sequences (Fig. 1). Compounds A1, A2,13 and B1eB4 are
designed, each of which possesses two amidourea units (Fig. 2).
Monomers A1 and A2 have the same DDAADD hydrogen-bonding
sequence but differ in the spacers, while monomers B1eB4 have
the same ADDDDA hydrogen-bonding sequence but differ in the
spacers and termini. In all the compounds, the octyloxy groups
were introduced for the formation of highly favorable S(6)-type18
intramolecular hydrogen bonds, which should preorganize the
amidourea units to facilitate the formation of heteroduplexes. The
synthesis of monomers B2eB4 is outlined in Scheme 1. Compound
B2 was conveniently synthesized by the reaction of compound 1
and 1,3-diaminopropane in chloroform. Compound 3, which was
prepared from hydrazide derivative 2 and 1,10-carbonyldiimidazole
efficiently, was reacted with 1,3-diaminopropane in refluxed
chloroform to yield compound B3. Compound B4 was obtained by
the reaction of hydrazide derivative 4 with 1,3-phenylene diiso-
cyanate in high yield.
Fig. 2. Chemical structures and proton designations of amidourea derivatives A1, A2, and B1eB4.
2.2. Amidourea-based heteroduplexes with tunable confor-
mation and stability
mation of heteroduplexes A1$B2 and A2$B2 were provided by
NOESY studies19 in CDCl3. Important cross-peaks were observed
between A1-Hc and B2-Hd, A1-Hd and B2-Hc in a 1:1 mixture of A1
and B2 (each at 5.0 mM), and between A2-Hd and B2-Hc, A2-Hd and
B2-Hi in a 1:1 mixture of A2 and B2, which were fully consistent
with the heteroduplex structures. Another direct evidence came
We have elucidated that amidourea derivatives A1 and A2, re-
spectively, self-assembled into hydrogen-bond-mediated supra-
molecular polymeric zipper structures, but the self-association of

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W.-J. Chu, C.-F. Chen / Tetrahedron 68 (2012) 9200e9205
Scheme 1. Synthesis of compounds B2eB4.
Fig. 3. Stacked partial 1H NMR spectra (300 MHz) of B2 at different concentrations in
CDCl3 at 298 K, showing the chemical shifts of Ha, Hb, and Hc.
Fig. 4. Stacked partial 1H NMR spectra (300 MHz, 298 K) of (a) A1 (red), (b) A1þB2, (c)
B2 (blue), (d) A2þB2, (e) A2 (pink), each at 5.0 mM in CDCl3.
from mass spectrometry. When 1:1 mixtures of A1 and B2, or A2
and B2 were analyzed by the APCI-MS,19 strong signals corre-
sponding to the heteroduplexes (1361.23 for [A1$B2þH]þ, 1411.21
for [A2$B2þH]þ) were shown. The binding stabilities of A1 and B2,
and A2 and B2 were investigated by 1H NMR titration methods
using B2 upon addition of A1 or A2 from 1:0 to 1:2 at 1.0 mM in
CDCl3. A fit of the chemical shift data for NHb proton of B2 to a 1:1
binding mode yielded association constants Ka of (7.1ꢀ0.7)ꢁ
103 Mꢂ1 for heteroduplex A1$B2 and (4.7ꢀ0.8)ꢁ103 Mꢂ1 for het-
eroduplex A2$B2, respectively.19,20 It was noteworthy that ami-
dourea derivatives A2 and B2 possessed more matched spacers
than A1 and B2, but heteroduplex A2$B2 had lower stability than
A1$B2. It should be caused by the enlarged spacers from A1 to A2,
while the heteroduplexes maintained the same hydrogen-bonding
sequence.
Similarly, 1H NMR studies on the 1:1 mixtures of A1 and B3, and
A2 and B3 (each at 5.0 mM) in CDCl3, respectively, both showed
significant downfield shifts for all the NH proton signals of A1 and
B3, and A2 and B3 (Fig. 6), which indicated the formation of het-
eroduplexes A1$B3 and A2$B3. The optimized conformations of
these heteroduplexes by DFT calculation revealed very similar re-
sults to those of heteroduplexes A1$B2 and A2$B2, with the only
difference in terminus between B2 and B3 (Fig. 7), which meant
that the terminus of monomer did not affect the binding motif of
these amidourea-based heteroduplexes. NOESY studies19 in CDCl3
provided diagnostic evidences for the formation of heteroduplexes
A1$B3 and A2$B3, in which intermolecular contacts were observed
between A1-Hb and B3-Hb, A1-Hb and B3-Hc, A1-Hc and B3-Hb in

W.-J. Chu, C.-F. Chen / Tetrahedron 68 (2012) 9200e9205
9203
Fig. 5. Optimized structures of heteroduplexes A1$B2 and A2$B2. All the side chains of monomers A1, A2, and B2 are replaced with methyl groups for simplicity.
suggested the formation of heteroduplexes A1$B4 and A2$B4. The
optimized structures by DFT calculation revealed that these two
heteroduplexes also maintained the amidourea-binding motif
(Fig. 9). Although B4 possessed the more rigid phenylene spacer, it
was able to adjust its conformation to adopt bending conforma-
tions to complex with A1 and A2. The formation of heteroduplexes
A1$B4 and A2$B4 was unequivocally evidenced by NOESY studies19
in CDCl3. Cross-strand contacts between A1-Hb and B4-Hb, A1-Hc
and B4-Hb, A1-Hd and B4-Hh in a 1:1 mixture of A1 and B4, and
between A2-Hb and B4-Hb, A2-Hd and B4-Hc, A2-Hd and B4-Hh
were observed, which were consistent with the heteroduplex
structures. The formation of the heteroduplexes was also evidenced
by APCI-MS,19 in which peaks of high intensity corresponding to the
heteroduplexes (1395.28 for [A1$B4þH]þ, 1445.15 for [A2$B4þH]þ)
were shown. When the binding stabilities of heteroduplexes A1$B4
and A2$B4 were investigated by 1H NMR titration studies in CDCl3,
the NH proton signals were overlapped with the aromatic proton
signals, so we could not obtain the association constants of these
two heteroduplexes from the chemical shifts of the NH protons. But
we believe that heteroduplexes A1$B4 and A2$B4 have similar high
stabilities to the other amidourea-based heteroduplexes, since they
all possess the similar hydrogen-bonding patterns.
Fig. 6. Stacked partial 1H NMR spectra (300 MHz, 298 K) of (a) A1 (red), (b) A1þB3, (c)
B3 (blue), (d) A2þB3, (e) A2 (pink), each at 5.0 mM in CDCl3.
Fig. 7. Optimized structures of heteroduplexes A1$B3 and A2$B3. All the side chains of monomers A1, A2, and B3 are replaced with methyl groups for simplicity.
a 1:1 mixture of A1 and B3, and between A2-Hd and B3-Hc, A2-Hd
and B3-Hk in a 1:1 mixture of A2 and B3. APCI-MS19 also showed
peaks of high intensity corresponding to the heteroduplexes
(1461.29 for [A1$B3þH]þ, 1511.83 for [A2$B3þH]þ). 1H NMR titra-
tion studies in CDCl3 afforded the association constants of
(3.1ꢀ0.3)ꢁ103 Mꢂ1 for heteroduplex A1$B3 and (2.1ꢀ0.5)ꢁ103 Mꢂ1
for heteroduplex A2$B3.19,20 The binding stability of heteroduplex
A2$B3 was still lower than that of A1$B3, although monomers A2
and B3 possessed more matched spacers.
As investigated above, amidourea derivatives B2eB4 were able
to adjust their conformations to achieve an optimal binding module
with their complementary partners A1 and A2. Consequently, all
the heteroduplexes adopted similar hydrogen-bonding patterns
through eight intermolecular bifurcated hydrogen bonds based on
the amidourea motif. The association constants of the heterodu-
plexes are summarized in Table 1. It was found that the heterodu-
plexes all possess moderate to high binding stabilities, and their
stabilities could be well tuned by the spacers and termini of the
monomers, while maintaining the same hydrogen-bonding se-
quences. When the spacers of the monomers were enlarged, in-
cluding changing from methylene to propylene such as from A1$B1
Mixing equimolar of A1 and B4, and A2 and B4 (5.0 mM) in
CDCl3, respectively, also led to obvious downfield shifts for all the
NH proton signals of A1 and B4, and A2 and B4 (Fig. 8), which

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W.-J. Chu, C.-F. Chen / Tetrahedron 68 (2012) 9200e9205
derivatives, and investigated their structures and association sta-
bilities in details. Although the amidourea derivatives possessed
different spacers or termini, it was found that theycould adjust their
conformations toachievean optimal binding module. Consequently,
all the heteroduplexes adopted similar hydrogen-bonding patterns
through eight intermolecular bifurcated hydrogen bonds based on
the amidourea motif. Moreover, the binding stabilities of the het-
eroduplexes could be well tuned by varying the spacers or termini of
the monomers. The ready synthetic accessibility and tunable asso-
ciation stability will make the amidourea-based hydrogen-bonded
heteroduplexes potentially applicable in the design of well-defined
supramolecular systems and novel functional materials.
4. Experimental
4.1. Synthesis
Compounds A1, A2, B1,13 1, 4,12a and 211d were synthesized, re-
spectively, according to the previous methods.
4.2. Compound B2
Fig. 8. Stacked partial 1H NMR spectra (300 MHz, 298 K) of (a) A1 (red), (b) A1þB4, (c)
B4 (blue), (d) A2þB4, (e) A2 (pink), each at 5 mM in CDCl3.
A
mixture of compound
1 (0.61 g, 2.1 mmol) and 1,3-
diaminopropane (74 mg, 1.0 mmol) was refluxed in CHCl3 (30 mL)
Fig. 9. Optimized structures of heteroduplexes A1$B4 and A2$B4. All the side chains of monomers A1, A2, and B4 are replaced with methyl groups for simplicity.
for 12 h. Then the solvent was evaporated under reduced pressure.
The residue was recrystallized with acetonitrile to afford com-
Table 1
Association constants of the heteroduplexes in CDCl3 at 298 K
pound B2 (0.55 g, 84%) as a white solid. Mp: 161e162 ꢃC. 1H NMR
Heteroduplex
Ka [Mꢂ1
]
(300 MHz, CDCl3):
d
9.61 (d, J¼3.4 Hz, 2H), 8.30 (s, 2H), 8.22
A1$B113
A1$B2
A2$B2
A1$B3
A2$B3
(1.6ꢀ0.1)ꢁ104
(7.1ꢀ0.7)ꢁ103
(4.7ꢀ0.8)ꢁ103
(3.1ꢀ0.3)ꢁ103
(2.1ꢀ0.5)ꢁ103
(dd, J¼7.8, 1.7 Hz, 2H), 7.51e7.41 (m, 2H), 7.10e7.00 (m, 2H), 7.00
(d, J¼8.3 Hz, 2H), 5.80 (t, J¼5.3 Hz, 2H), 4.13 (t, J¼6.8 Hz, 4H),
3.53e3.41 (m, 4H), 1.97e1.82 (m, 6H), 1.54e1.21 (m, 20H), 0.88
(t, J¼6.9 Hz, 6H). 13C NMR (75 MHz, CDCl3):
d 166.5, 158.7, 157.4,
133.5, 132.4, 121.0, 119.3, 112.3, 69.4, 39.1, 31.7, 29.2, 29.1, 29.0, 28.3,
25.9, 22.6, 14.0. APCI-MS: m/z 655.97 [MþH]þ. Anal. Calcd for
C35H54N6O6: C, 64.20; H, 8.31; N, 12.83. Found: C, 64.24; H, 8.23;
N, 13.00.
to A1$B2, and changing from phenylene to naphthalene such as
from A1$B2 to A2$B2 or from A1$B3 to A2$B3, the association
constants of the heteroduplexes decreased significantly. When the
termini of the monomers were enlarged from phenyl to naphthyl
such as from A1$B2 to A1$B3 or from A2$B2 to A2$B3, the associ-
ation constants of the heteroduplexes also decreased obviously.
When the spacers and termini of the monomers were enlarged at
the same time, such as from A1$B1 to A1$B3 or from A1$B2 to
A2$B3, the association constants of the heteroduplexes would de-
crease much more. The strategy to well tune the association sta-
bility of the hydrogen-bonded duplexes by varying the spacers or
termini of the monomers as demonstrated here may be extended to
other multiply hydrogen-bonded systems.
4.3. Compound 3
A mixture of compound 2 (0.63 g, 2.0 mmol) and 1,10-carbon-
yldiimidazole (0.34 g, 2.1 mmol) in dry CH2Cl2 (20 mL) was stirred
at room temperature for 6 h. Then the solution was washed with
water, and dried over anhydrous sodium sulfate. Removal of the
solvent under reduced pressure afforded compound 3 (0.66 g, 97%)
as a white solid. Mp: 138e139 ꢃC. 1H NMR (300 MHz, CDCl3):
d 9.01
(s, 1H), 8.27 (s, 1H), 7.83 (d, J¼8.1 Hz, 1H), 7.74 (d, J¼8.2 Hz, 1H),
7.57e7.48 (m, 1H), 7.44e7.35 (m, 1H), 7.24 (s, 1H), 4.20 (t, J¼6.6 Hz,
2H),1.99e1.85 (m, 2H),1.61e1.47 (m, 2H),1.44e1.22 (m, 8H), 0.88 (t,
3. Conclusions
J¼6.9 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d 154.9, 154.2, 154.0, 135.8,
130.8, 128.6, 128.5, 127.7, 126.5, 124.6, 114.3, 107.7, 69.0, 31.8, 29.3,
In conclusion, we have constructed a class of multiply hydrogen-
bonded heteroduplexes from readily available amidourea
29.2, 28.9, 25.9, 22.6, 14.1. ESI MS: m/z 341.44 [MþH]þ. Anal. Calcd

W.-J. Chu, C.-F. Chen / Tetrahedron 68 (2012) 9200e9205
9205
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4.4. Compound B3
A
mixture of compound 3 (0.71 g, 2.1 mmol) and 1,3-
diaminopropane (74 mg, 1.0 mmol) was refluxed in CHCl3 (30 mL)
for 24 h. Then the solvent was evaporated under reduced pressure.
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(0.62 g, 82%) as a white solid. Mp: 204e205 ꢃC. 1H NMR (300 MHz,
5. (a) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.; Hirschberg, J. H. K.
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J¼8.1 Hz, 2H), 7.70 (d, J¼8.2 Hz, 2H), 7.57e7.47 (m, 2H), 7.43e7.34 (m,
2H), 7.17 (s, 2H), 5.90 (s, 2H), 4.19 (t, J¼6.7 Hz, 4H), 3.58e3.45 (m, 4H),
2.03e1.85 (m, 6H),1.57e1.21 (m, 20H), 0.88 (t, J¼6.8 Hz, 6H).13C NMR
(75 MHz, CDCl3): d 166.5,158.7,154.1,136.1,134.2,129.2,128.5,128.0,
126.2, 124.5, 120.2, 107.4, 69.4, 39.6, 31.8, 29.3, 29.2, 28.9, 28.1, 26.0,
22.6,14.1. APCI-MS: m/z 756.13 [MþH]þ. Anal. Calcd for C43H58N6O6:
C, 68.41; H, 7.74; N, 11.13. Found: C, 68.46; H, 7.77; N, 11.29.
4.5. Compound B4
A mixture of compound 4 (0.56 g, 2.1 mmol) and 1,3-phenylene
diisocyanate (0.16 g, 1.0 mmol) in dry CH2Cl2 (20 mL) was stirred at
room temperature for 8 h. Then the solvent was evaporated under
reduced pressure. The residue was recrystallized from acetonitrile
to give the product (0.63 g, 92%) as a white solid. Mp: 189e190 ꢃC.
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1H NMR (300 MHz, CDCl3):
d 9.98 (s, 2H), 8.90 (s, 2H), 8.23e7.93 (m,
4H), 7.39e7.28 (m, 2H), 7.06 (s, 2H), 6.98e6.89 (m, 2H), 6.89e6.74
(m, 4H), 4.05 (t, J¼6.6 Hz, 4H), 1.96e1.82 (m, 4H), 1.52e1.18 (m,
20H), 0.85 (t, J¼6.7 Hz, 6H). 13C NMR (75 MHz, CDCl3):
d 166.0,
157.0, 155.0, 138.4, 133.0, 131.8, 128.5, 120.5, 119.1, 113.5, 111.8, 110.4,
69.1, 31.5, 29.0, 28.9, 28.8, 25.7, 22.3, 13.8. APCI-MS: m/z 690.02
[MþH]þ. Anal. Calcd for C38H52N6O6: C, 66.26; H, 7.61; N, 12.20.
Found: C, 66.29; H, 7.53; N, 12.35.
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in press.
4.6. Theoretical calculation
All the theoretical calculations were performed with density
functional theory (DFT) at the B3LYP/6-31þG(d,p) level employing
the Gaussian 09 software.21 For all the heteroduplexes, the geom-
etries were completely optimized, which corresponded to the en-
ergy minimum. The total electronic energy of the hydrogen-bonded
heteroduplex was the basis set superposition error (BSSE) corrected
energy.22
14. Jorgensen, W. L.; Pranata, J. J. Am. Chem. Soc. 1990, 112, 2008e2010.
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Chem., Int. Ed. 1998, 37, 75e78; (b) Hirschberg, J. H. K.; Brunsveld, L.; Ramzi, A.;
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Acknowledgements
We are grateful to the National Natural Science Foundation of
China (91127009), and the National Basic Research Program of
China (2011CB932501) for financial support.
18. Etter, M. C. Acc. Chem. Res. 1990, 23, 120e126.
19. See Supplementary data for details.
20. Connors, K. A. Binding Constants: The Measurement of Molecular Complex Sta-
bility; Wiley-Interscience: New York, NY, 1987.
Supplementary data
21. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.;
Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.;
Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Ha-
segawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers,
E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N.
J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gom-
perts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.;
Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.;
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.08.092.
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