Pyridine-imide oligomers

Article abstract of DOI:10.1039/b800020d

Pyridine-imide oligomers created by incorporating imide and pyridine units alternatively in sequence were successfully synthesized and found to form highly compact and stable helical conformations contributed by intramolecular H-bonds between the imide and both adjacent pyridines, and by the structural characteristics of the imide units. The Royal Society of Chemistry.

Full text of DOI:10.1039/b800020d

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Pyridine–imide oligomersw
Xiao Li,ab Chuanlang Zhan,* Yaobing Wang and Jiannian Yao*a
a
ab
Received (in Cambridge, UK) 9th January 2008, Accepted 27th March 2008
First published as an Advance Article on the web 21st April 2008
DOI: 10.1039/b800020d
Pyridine–imide oligomers created by incorporating imide and
pyridine units alternatively in sequence were successfully synthe-
sized and found to form highly compact and stable helical
conformations contributed by intramolecular H-bonds between
the imide and both adjacent pyridines, and by the structural
characteristics of the imide units.
dynamics, conformations, and structures of the oligomers is as
yet unknown.
In this communication, we introduce imide as a functional
H-bonding unit incorporated with pyridine together to devel-
op pyridine–imide oligomers with highly compact and stable
helical conformations (Fig. 1). The imide-NH was found to H-
bond with both adjacent pyridine nitrogen atoms intramole-
cularly and then produce consecutive bends along the strand.
The high compactness is contributed from both intramolecular
H-bonds and structural characteristics of the imide itself.
The oligomers were successfully synthesized by refluxing the
corresponding primary amide and acid chloride prepared from
commercial 2,6-pyridinedicarboxylic acid. In brief, refluxing
of 2-ethoxycarbonyl-6-pyridinoyl chloride (1) and 2-ethoxy-
carbonyl-6-pyridinoyl amide (2) in toluene gave PIO1, while
PIO2 was obtained from 2 and 2,6-pyridinoyl dichloride (3).
PIO3 was obtained from the PIO1-monoamide and PIO1-
monoacyl chloride converted from PIO1 as starting materials
The a-helix widely occurs in nature and is related to the
extensive biological functions of proteins. Foldamers have
been created with chemically diverse units from aliphatics to
aromatics in the past decades to mimic a-helices in either
1
structure or function. In contrast to the aliphatic homolo-
2
,3
gues, which may tightly pack into highly compact structures
such as the a-peptides, most of the reported aromatic oligo-
1
c,4,5
amides (AOAs)
are still far from high compactness
although the AOAs possess advanced structural features such
as structural predictability and canonical helical conforma-
tions. Considering the rigidity and high coplanarity of the
aromatics, there remain challenges to create highly compact
helical conformations for AOAs. Reported cases include those
generated by adjusting the relative orientations of substituted
amine and acid groups from 1201 (at pyridine) to 601 (at
(Fig. 2).
1
H NMR studies in CDCl solution (Fig. 3) show the imide
3
protons of PIO1 are deshielded at 12.96 ppm, much more
downfield of values characteristic of intramolecularly non-H-
11
bonded or H-bonded imide protons, or H-bonded amide
6
4d
quinoline or benzene ).
1
2
As H-bonding functional linkages, amide units have been
widely used in constructions of AOAs as the NHCO–aryl
rotation may be restricted into a strong preference of anti- or
protons of dimeric pyridine–oligoamides. This strongly sug-
gests that the imide-protons intramolecularly H-bond to both
adjacent pyridine nitrogen atoms, as further supported by the
slight upfield shifting (0.3 ppm) of the imide-protons in
5c,7
syn-conformation with H-bonds. Other linkages such as urea
8
and hydrazide have also been reported. 2-Ureopyridine may
exist as a balance between cis and trans conformers, which
may result in an equilibrium for oligomers between the inter-
molecularly H-bonded linear dimers and intramolecularly
H-bonded helical monomers. Although hydrazide was found
to favor a trans-conformation, the oligomers seem to adopt
linear conformations rather than helical conformations. In
contrast, imide groups are rarely utilized as linkages (three
reported cases were related to N-substituted imidyl–benzene
6
d -DMSO. Moreover, it is surprising that the intramolecularly
H-bonded imide-protons are remarkably stable to DIEA
9
,10
and –naphthalene based oligomers ). Most importantly,
how the imide groups act as H-bonding linkages to regulate
a
Beijing National Laboratory for Molecular Sciences (BNLMS),
Institute of Chemistry, Chinese Academy of Sciences, Beijing,
100190, People’s Republic of China. E-mail: clzhan@iccas.ac.cn;
jnyao@iccas.ac.cn; Fax: +86-10-82616517; Tel: +86-10-82616517
Graduate University of the Chinese Academy of Sciences (GUCAS),
Beijing, 100049, People’s Republic of China
b
Fig. 1 Comparison of (a) a-peptide and (b) pyridine–imide oligo-
mers: alternative three-atom sequences are colored blue and green
along the backbone direction (in the inner rim). (c) A helical structure
showing intramolecular H-bonds between imide-NH and both adja-
cent pyridine nitrogen atoms. (d) Chemical structures of pyridine–
imide oligomers.
w Electronic supplementary information (ESI) available: Detailed
experimental procedures, characterizations of all new compounds
1
13
(
H, C NMR and MS). CCDC 674807 and 674808. For ESI and
crystallographic data in CIF or other electronic format see DOI:
0.1039/b800020d
1
2
444 | Chem. Commun., 2008, 2444–2446
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1
Fig. 3 Part of the 400 MHz H NMR spectra of PIO1 (a), PIO2 (b)
and PIO3 (c).
acter of the C–N bond. The imide-NH forms into two
intramolecular H-bonds with both adjacent pyridine nitrogen
atoms, generating consecutive bends along the strand. The
bending curvature is also contributed from the structural
characteristics of the imide groups, as indicated by the bond
angles of +C(imide)–N(imide)–C(imide) (126.25–129.481) and
Fig. 2 Synthetic procedure for pyridine–imide oligomers. Reagents
and conditions: (a) ethanol, H SO , reflux, 8 h, 94%; (b) NaOH,
ethanol, 1,4-dioxane, 70–80%; (c) SOCl ; (d) NH /CH Cl , RT,
; (f) toluene/reflux, 8 h, 80–95%; (g) toluene/reflux,
h, 10–20%; (h) NaOH, 1,4-dioxane, 25–35%; (i) SOCl ; (j)
/CH Cl , RT, 90%; (k) toluene/reflux, 8 h, 10–15%.
2
4
+N(imide)–C(imide)–C(pyridine) (111.55–113.781). Interest-
2
3
2
2
ingly, the crystal structures give three surprising findings. The
first is that PIO2 crystallises in a chiral space group, in which a
crystal cell accommodates four left-handed helices. This sug-
gests that the racemic oligomers undergo spontaneous resolu-
tion into the two enantiomers. This feature is very uncommon
in helical molecules. The second is that the imide groups in
PIO3 have higher coplanarity than in PIO2, as revealed by the
torsion angles of O(imide)–C(imide)–N(imide)–C(imide). The
third is that PIO3 exhibits a more bent conformation than
PIO2. For example, the +C(imide)–N(imide)–C(imide)s are
nearly 0.6–3.21 smaller in PIO2 (126.25 and 127.831) than in
PIO3 (128.41, 128.99, 129.481). The +N(imide)–C(imide)–
C(pyridine) angles are in the range of 112.54–113.641 in
PIO2, while decrease to 111.55–112.471 (with an exception
of 113.781) among six values in PIO3, although they are
9
5%; (e) SOCl
2
8
2
NH
3
2
2
1
diisopropylethyl amine), as revealed by H NMR study on
(
adding DIEA into the PIO1/CDCl solution.
3
With chain length increase from PIO1 to PIO2 to PIO3,
both similarities and distinct differences were observed in the
1
H NMR spectra (Fig. 3). PIO1, PIO2 and PIO3 all show
sharp signals and no indications of double-helix formation or
other types of aggregates, even at temperatures down to 223 K
(
Fig. 4). This is different from the behavior of pyridine–oligo-
4
6
amides, but similar to that of quinoline–oligoamides. On the
other hand, the protons of PIO1, PIO2 and PIO3 show
distinct shifting in the NMR range, a reflection of helical
conformations, for example, the upfield shifting of both ethyl-
protons of PIO2 or PIO3 and terminal imide protons (appear-
ing at 12.64 ppm) of PIO3, evidenced shielding effects from the
pyridines in a helical structure. The helical conformations are
further confirmed by NOE experiments, particularly, by the
strong NOE contacts between terminal ethyl protons or imide-
protons and pyridine-protons for both PIO2 and PIO3 and
the contacts between central and terminal imide-protons for
PIO3, an obvious reflection of the formation of compact
helical conformations (Fig. 5).
1
All the H NMR data above are consistent with compact
helical conformations in solutions. Crystals suitable for the
single-crystal X-ray diffraction analysis were obtained for both
1
3
14
PIO2 and PIO3. The resolved structures agree well with
molecular modeling (Gauss MM2) and solution structures. As
expected, the imide units show high coplanarity. The imide
˚
C–N lengths are nearly identical in the range of 1.368–1.388 A
˚
1
Fig. 4 Partial 600 MHz H NMR spectra of PIO2 (upper) and PIO3
with the CQO bond lengths ranging from 1.196 to 1.207 A,
indicating high electron delocalization and double-bond char-
(lower) at three different temperatures.
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the National Research Fund for Fundamental Key Project 973
(
2006CB806200, 2007CB936401).
Notes and references
1
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For recent examples of b, g, d-peptides, see: (a) E. A. Porter, X. F.
Wang, H. S. Lee, B. Weisblum and S. H. Gellman, Nature, 2000,
4
04, 565–565; (b) J. A. Kritzer, J. D. Lear, M. E. Hodsdon and A.
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Qiu and A. Schepartz, J. Am. Chem. Soc., 2007, 129, 1532–1533.
For examples of hybrid peptides, see: (a) G. V. M. Sharma, P.
Nagendar, P. Jayaprakash, P. R. Krishna, K. V. S. Ramakrishna
and A. C. Kunwar, Angew. Chem., Int. Ed., 2005, 44, 5878–5882;
3
(
b) P. G. Vasudev, K. Ananda, S. Chatterjee, S. Aravinda, N.
Fig. 5 Solid-state structures of PIO2 (upper) and PIO3 (lower): side-
view (left) and top-view (right) with the imide units colored in green.
The hydrogen atoms except for the imide protons are omitted for
clarity.
Shamala and P. Balaram, J. Am. Chem. Soc., 2007, 129,
4039–4048; (c) S. H. Choi, I. A. Guzei and S. H. Gellman, J.
Am. Chem. Soc., 2007, 129, 13780–13781.
For examples, see: (a) V. Berl, I. Huc, R. G. Khoury, M. J. Krische
and J. M. Lehn, Nature, 2000, 407, 720–723; (b) V. Berl, I. Huc, R.
G. Khoury and J. M. Lehn, Chem.–Eur. J., 2001, 7, 2798–2809; (c)
V. Berl, I. Huc, R. G. Khoury and J. M. Lehn, Chem.–Eur. J.,
2001, 7, 2810–2820; (d) C. A. Hunter and D. H. Purvis, Angew.
Chem., Int. Ed. Engl., 1992, 31, 792–795.
4
5
dependent on either the position in the sequence or the chain
length. The above two structural differences between PIO2
and PIO3 are likely due to the ‘‘structural tunability’’—the
bond and torsion angles—of the imide unit, which is sensitive
to interactions between the stacking units in the helical
structures, for example, the i imide is shown to stack partially
with the pyridine positioning at i + 5 and partially with
another imide at i + 4.
For examples see: (a) B. Gong, Chem.–Eur. J., 2001, 7, 4336–4342;
(
b) J. L. Hou, H. P. Yi, X. B. Shao, C. Li, Z. Q. Wu, X. K. Jiang, L.
Z. Wu, C. H. Tung and Z. T. Li, Angew. Chem., Int. Ed., 2006, 45,
96–800; (c) R. W. Sinkeldam, F. J. M. Hoeben, M. J. Pouderoijen,
7
I. De Cat, J. Zhang, S. Furukawa, S. De Feyter, J. Vekemans and
E. W. Meijer, J. Am. Chem. Soc., 2006, 128, 16113–16121.
(a) H. Jiang, J. M. Leger and I. Huc, J. Am. Chem. Soc., 2003, 125,
´
3448–3449; (b) E. R. Gillies, F. Deiss, C. Staedel, J.-M. Schmitter
and I. Huc, Angew. Chem., Int. Ed., 2007, 46, 4081–4084.
(a) N. C. Singha and D. N. Sathyanarayana, J. Chem. Soc., Perkin
Trans. 2, 1997, 157–162; (b) P. S. Corbin and S. C. Zimmerman, J.
Am. Chem. Soc., 2000, 122, 3779–3780; (c) P. S. Corbin, S. C.
Zimmerman, P. A. Thiessen, N. A. Hawryluk and T. J. Murray, J.
Am. Chem. Soc., 2001, 123, 10475–10488.
6
7
As expected, the pyridine–imide oligomers possess compact
helical conformations with every five units constituting a
helical turn, that is each turn contains about 15 atoms along
the backbone (in the inner rim). Considering the coplanarity
and rigidity of the constituent units, this corresponding to the
highest curvature reached by AOAs. The imide protons all fill
the helix hollow and prevent solvent molecules penetrating
through it. All imide oxygen atoms position outward the helix.
Additionally, the homologous units positioning at i and i + 5
sites in sequence are arranged in an orderly manner along the
helical axis, for example, the imide units at 2 and 7 positions.
8
J. Garric, J. M. Le
Tetrahedron Lett., 2003, 44, 1421–1424.
9 J. M. Rodriguez and A. D. Hamilton, Angew. Chem., Int. Ed.,
007, 46, 8614–8617.
´
ger, A. Grelard, M. Ohkita and I. Huc,
2
1
0 (a) H. Masu, M. Sakai, K. Kishikawa, M. Yamamoto, K. Yama-
guchi and S. Kohmoto, J. Org. Chem., 2005, 70, 1423–1431; (b) L.
S. Evans and P. A. Gale, Chem. Commun., 2004, 1286–1287.
˚
The helical pitch is 3.4 A, similar to the pyridine–oligoamides
11 (a) J. Dai, C. S. Day and R. E. Noftle, Tetrahedron, 2003, 59,
389–9397; (b) C. D. Vanderwal and E. N. Jacobsen, J. Am. Chem.
9
and related to the thickness of one aromatic ring. The relative
inclinations of the helix are contributed by both the torsions
between the pyridine and the imide units and the imide unit
itself. The inclinations can be estimated from the torsion
angles of each consecutive four-inner-rim-atoms between the
nitrogen atoms of two pyridines attached to one imide unit.
In summary, both solution- and solid-state studies reveal
the pyridine–imide oligomers form into remarkably stable and
compact helical conformations. On basis of the advanced
features—stability and compactness, further study will focus
on possible bio-applications and electron/energy transfer
properties through the bridged oligomeric strand.
Soc., 2004, 126, 14724–14725; (c) T. Inokuma, Y. Hoashi and Y.
Takemoto, J. Am. Chem. Soc., 2006, 128, 9413–9419.
12 C. Dolain, C. L. Zhan, J. M. Leger, L. Daniels and I. Huc, J. Am.
´
Chem. Soc., 2005, 127, 2400–2401.
3 Crystal data for PIO2: crystallization solvent/precipitant: DMF/
1
diethyl ether, orthorhombic, space group P2
˚
1
2
1
2
1
, colorless, a =
.7201(14), b = 8.3506(15), c = 37.025(7) A, T = 113(1) K, Z =
7
4, GOF = 1.037. The final R indices were R1 (I 4 2s(I)) = 0.0312,
wR2 (all data) = 0.0750.
4 Crystal data for PIO3: crystallization solvent/precipitant: DMF/
1
ꢀ
diethyl ether, triclinic, space group P1, colorless, a = 11.556(2), b
˚
= 12.222(2), c = 12.249(2) A
, a = 67.75(3), b = 82.17(3), g =
8
8.75(3), Z = 2, T = 298 K, GOF = 1.149. The final R indices
were R1 (I 4 2s(I)) = 0.0983, wR2 (all data) = 0.2085. The poor
quality of this structure is due to weak diffraction intensity and
disorder of the terminal ethyl units. However, all atoms relative to
the backbone of the helix were accurately located.
We thank NSFC (Nos. 50221201, 90301010, 20471062,
5
0573084, 20303024), the Chinese Academy of Sciences, and
2
446 | Chem. Commun., 2008, 2444–2446
This journal is ꢀc The Royal Society of Chemistry 2008