Backbone conformation affects duplex initiation and duplex propagation in hybridisation of synthetic H-bonding oligomers

Article abstract of DOI:10.1039/c8ob00819a

Synthetic oligomers equipped with complementary H-bond donor and acceptor side chains form multiply H-bonded duplexes in organic solvents. Comparison of the duplex forming properties of four families of oligomers with different backbones shows that format

Full text of DOI:10.1039/c8ob00819a

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Backbone conformation affects duplex initiation
and duplex propagation in hybridisation of
synthetic H-bonding oligomers†
Cite this: DOI: 10.1039/c8ob00819a
Giulia Iadevaia,
Diego Núñez-Villanueva,
Alexander E. Stross and
Christopher A. Hunter
*
Synthetic oligomers equipped with complementary H-bond donor and acceptor side chains form multi-
ply H-bonded duplexes in organic solvents. Comparison of the duplex forming properties of four families
of oligomers with different backbones shows that formation of an extended duplex with three or four
inter-strand H-bonds is more challenging than formation of complexes that make only two H-bonds. The
stabilities of 1 : 1 complexes formed between length complementary homo-oligomers equipped with
either phosphine oxide or phenol recognition modules were measured in toluene. When the backbone is
very flexible (pentane-1,5-diyl thioether), the stability increases uniformly by an order of magnitude for
each additional base-pair added to the duplex: the effective molarities for formation of the first intra-
molecular H-bond (duplex initiation) and subsequent intramolecular H-bonds (duplex propagation) are
similar. This flexible system is compared with three more rigid backbones that are isomeric combinations
of an aromatic ring and methylene groups. One of the rigid systems behaves in exactly the same way as
the flexible backbone, but the other two do not. For these systems, the effective molarity for formation of
the first intramolecular H-bond is the same as that found for the other two backbones, but additional
H-bonds are not formed between the longer oligomers. The effective molarities are too low for duplex
propagation in these systems, because the oligomer backbones cannot adopt conformations compatible
with formation of an extended duplex.
Received 6th April 2018,
Accepted 30th April 2018
DOI: 10.1039/c8ob00819a
rsc.li/obc
phosphine oxide recognition units.10 All combinations of
2-mers that have the N7, N8 and C8 backbones shown in Fig. 1
Introduction
Nucleic acids store and express genetic information via form duplexes with similar stabilities.10b,d In fact, the effective
sequence selective duplex formation and template directed molarities for formation of the intramolecular H-bonds that
synthesis.1 Variation in the chemical structure of the back- lead to duplex formation in all of the systems shown in Fig. 1
bone,2 the base pairing system,3 the phosphate diester linker4 are remarkably similar (7–20 mM).11 These results suggest that
and the sugar5 have been explored, and the ability to form a conformational properties of the backbone are not critical for
stable duplex is maintained despite these modifications. This duplex formation, so oligomers with the highly flexible C9
observation suggests that oligomers with very different chemi- backbone form duplexes that have similar stability to the
cal structures may also be able to form duplexes in a sequence duplexes formed by oligomers with the more rigid C8 back-
selective manner. A number of synthetic oligomers have been bone. Here we describe a new family of oligomers where the
reported that form duplexes through different types of non- conformational properties of the backbone compromise
covalent interaction, including metal–ligand coordination,6 duplex formation between longer oligomers.
aromatic stacking,7 salt bridges8 and H-bonding.9
The stepwise equilibria for the assembly of two complemen-
Fig. 1 shows the structures of four different H-bonded tary oligomers into a duplex are shown in Fig. 2.12 After the
duplexes formed by oligomers equipped with phenol and first intermolecular interaction, that has an association con-
stant of K, the subsequent intramolecular interactions have an
equilibrium constant of KEMN, where EMN is the stepwise
effective molarity, and N is the number of intramolecular inter-
actions formed. Fully bound duplexes are formed, if the values
of KEMN are all significantly greater than one. By comparing
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge
CB21EW, UK. E-mail: herchelsmith.orgchem@ch.cam.ac.uk
†Electronic supplementary information (ESI) available. CCDC 1835177. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
the stabilities of duplexes of increasing chain length, it is poss-
c8ob00819a
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ible to experimentally determine values of EMN. In this paper,
we show that the effective molarity for the first intramolecular
interaction responsible for duplex initiation (EM1) can be very
different from the values of EM for the subsequent intra-
molecular interactions that lead to duplex propagation.
The synthesis of the homo-oligomers up to four recognition
units in length was previously reported for the C8 and C9 back-
bones.10a Here we describe the synthesis of the corresponding
homo-oligomers with the N7 and N8 backbones. Measurement
of the stabilities of the duplexes formed by all complementary
pairs of oligomers allows characterisation of the stepwise
effective molarities for duplex initiation and propagation.
Results and discussion
Synthesis
A convergent approach was taken to obtain the oligomers from
a set of common building blocks. Secondary anilines 1a and 1b,
which were used as chain end caps, were prepared via reductive
amination of the corresponding primary anilines (Scheme 1).
The H-bond donor primary aniline, 4-aminophenol, is commer-
cially available, and synthesis of the H-bond acceptor primary
aniline bearing a phosphine oxide was reported previously.10b
Scheme 2 shows the synthetic route to the 3-mers and
4-mers for the N8 backbone. Monoprotected aldehyde 3 was
prepared by refluxing 2 with one equivalent of ethylene glycol
in toluene (Scheme 2).13 Aldehydes 4a and 4b were synthesized
by reductive amination of 3 with 1a or 1b, followed by acetal
deprotection (Scheme 2). 3-mers 5a and 5b were obtained by
reductive amination of 4a or 4b with the corresponding
primary aniline. The bisanilines 6a and 6b were prepared from
2 as described previously.10b Reductive amination of aldehyde
4a with aniline 6a gave the all donor 4-mer 7a, and reductive
amination of aldehyde 4b with aniline 6b gave the all acceptor
4-mer 7b.
Fig. 1 H-bonded duplexes. Different backbones lead to equally stable
2-mer duplexes. The C8 backbone is highlighted in purple, the N8 back-
bone in orange, the N7 backbone in green, and the C9 in blue. R is
2-ethylhexyloxy and R’ is n-hexyl.
Scheme 1
Fig. 2 Stepwise assembly of a duplex from two complementary oligomers. K is the association constant for formation of an intermolecular inter-
action between two complementary H-bonding sites, and EMN are the stepwise effective molarities for formation of the intramolecular interactions
that lead to zipping up of the duplex.
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Scheme 3
Scheme 2
Table 1 Association constants KN and limiting complexation-induced
changes in 31P NMR chemical shift for formation of 1 : 1 complexes in
toluene-d8 at 298 K
A similar synthetic route was used for the synthesis of the
N7 backbone oligomers (Scheme 3). Reductive amination of
monoprotected aldehyde 9 with 1a or 1b gave aldehydes 10a
and 10b respectively. The 3-mers 11a and 11b were obtained
by reductive amination of 10a or 10b with the corresponding
primary aniline. The bisanilines 12a and 12b were prepared
from 8 as described previously.10b Reductive amination of alde-
hyde 10a with 12a the all donor 4-mer 13a, and reductive
amination of aldehyde 10b with 12b gave the all acceptor
4-mers 13b (Scheme 3).
Backbone
Complex
log KN/M−1
Δδ 31P/ppm
—
A·D
AA·DD
AAA·DDD
AAAA·DDDD
AA·DD
AAA·DDD
AAAA·DDDD
2.4 0.1
3.4 0.1
3.5 0.2
3.8 0.1
3.1 0.2
3.4 0.1
3.3 0.1
5.0
3.9
3.8, 4.7
4.3, 4.3
6.9
7.6, 7.6
8.5, 8.6
N8
N8
N8
N7
N7
N7
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NMR binding studies
Association constants between complementary H-bond donor
(D) and H-bond acceptor (A) oligomers were determined via
31P NMR titrations in toluene-d8. In all cases, the H-bond
acceptor phosphine oxide oligomer was used as the host, and
the data fit well to 1 : 1 binding isotherms. The results are
summarized in Table 1, together with data for the corres-
ponding 1-mer and 2-mer complexes previously reported.10a,b,d
Table 1 also reports the complexation-induced changes in
chemical shift of the 31P signals. The large increases in 31P
chemical shift are characteristic of H-bond formation.14 The
association constants for the 3-mer complexes (AAA·DDD) and
for the 4-mer complexes (AAAA·DDDD) are of the same order
of magnitude as the association constant for the corres-
ponding 2-mer complexes (AA·DD) (Table 1).
Fig. 3 Relationship between the association constant for duplex for-
mation (log KN) and the number of recognition units in an oligomer (N)
for the C8 (purple),10a C9 (blue),10d N8 (orange) and N7 (green)
backbones.
Fig. 3 shows the relationship between the association con-
stant for duplex formation (log KN) and the number of poten-
Fig. 4 Lowest energy conformations of the 2-mer AA·DD duplexes from conformational searches (MMFFs force-field and CHCl3 solvation
implemented in Macromodel)15 for the (a) N8, (b) N7, (c) C8 and (d) C9 backbones. The H-bond donor oligomer is shown in red and the H-bond
acceptor oligomer in blue. The recognition modules are shown as atomic spheres, H-bonds are shown in yellow, and hydrogen atoms on carbon are
not shown for clarity. The chemical structures highlight the key interactions made in the calculated structures.
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tial H-bonding interactions (N). The association constants for are not stable. One would expect a corresponding difference
the C8 and C9 backbones increase uniformly by an order of in the magnitudes of the complexation-induced changes in
magnitude for each H-bonding site added to the chain. For 31P NMR chemical shift for the systems that are not fully
the N8 and N7 backbones, the 2-mer duplex is an order of H-bonded, but the changes in chemical shift are actually
magnitude more stable than the singly H-bonded 1-mer larger for the longer N8 and N7 oligomers. This discrepancy
complex, but there is no significant increase in association must reflect some difference in three-dimensional structure
constant for the 3-mer or 4-mer complexes. These results for these complexes or the formation of higher order aggre-
suggest that in the longer N8 and N7 oligomers only two gates that do not significantly affect the shape of the binding
H-bonds are formed and that the fully assembled duplexes isotherm.
Fig. 5 Lowest energy conformations of the 3-mer AAA·DDD duplexes from conformational searches (MMFFs force-field and CHCl3 solvation
implemented in Macromodel)15 for the (a) N8, (b) N7, (c) C8 and (d) C9 backbones. The H-bond donor oligomer is shown in red and the H-bond
acceptor oligomer in blue. The recognition modules are shown as atomic spheres, H-bonds are shown in yellow, and hydrogen atoms on carbons
are not shown for clarity. The chemical structures highlight the key interactions made in the calculated structures.
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Conformational analysis
molecular mechanic calculations.15 By using a distance con-
straint to make sure that at least one intermolecular H-bond is
formed in the duplex, it is possible to restrict the confor-
mational search space to a tractable size. Fig. 4 shows the
lowest energy structures obtained from conformational
searches for 2-mer AA·DD duplexes with the four different
backbones. In all cases, the fully assembled duplex with two
A·D H-bonds was found. Fig. 5 shows the lowest energy struc-
tures obtained from conformational searches for 3-mer
AAA·DDD duplexes with the four different backbones. In this
case, the fully assembled duplex with three A·D H-bonds was
found for the C8 and C9 backbones, but not for the N8 and N7
backbones. In the N8 and N7 backbone structures, only two of
the recognition units are properly paired. Moreover, the fully
H-bonded duplex with all three A·D H-bonds was not located
at all in the conformational search for either of these systems,
which suggests that this structure is considerably higher in
energy than the global energy minimum.
The difference in behaviour between the four different systems
is likely to be due to geometrical incompatibility of the N8 and
N7 backbones with the fully bound duplex. The geometrical
properties of the backbones were therefore investigated using
The computational results are consistent with the experi-
mental observations. All of the backbones are compatible
with formation of the first and second H-bond of the duplex,
but only the C8 and C9 backbones can make the third
H-bond. For the two complexes that do not form the fully
assembled duplex, the unsatisfied H-bond donor makes an
additional interaction with an alternative site. For the N8
backbone, the unpaired terminal phenol interacts with the
central phosphine oxide that is already engaged in a H-bond
with the complementary central phenol. For the N7 back-
bone, the unpaired terminal phenol interacts with the central
phenol that is already H-bonded to the complementary
central phosphine oxide. The experimental association con-
stants indicate that if these additional interactions are
Fig. 6 Conformation of the N8 backbone. (a) Chemical structure of the
AA 2-mer; (b) X-ray structure of the AA 2-mer; (c) conformation of the
AA 2-mer in the lowest energy molecular mechanics structure of the
AA·DD duplex; (d) conformation of the AAA 3-mer in the lowest energy
molecular mechanics structure of the AAA·DDD duplex. The first two
recognition modules that are H-bonded in the duplex are highlighted in
blue for comparison with (b) and (c), and the third recognition module
that is not involved in H-bonding in the duplex is shown in grey.
Fig. 7 Relationship between the conformational properties of the backbone and stepwise effective molarities in the formation of non-covalent
duplexes. (a) A rigid backbone will form a duplex if it is geometrically compatible. (b) A very flexible backbone will always be able find a confor-
mational state that is geometrically compatible with the duplex. (c) If a rigid backbone is not geometrically compatible with the duplex, the first
effective molarity for duplex initiation (EM1) and the subsequent effective molarities for duplex propagation (EM2) will be different, so only the 2-mer
duplex will assemble.
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present, then they do not contribute significantly to the stabi- duplex, even though the 2-mers behave in exactly the same way
lities of the complexes.
as the C8 and C9 2-mers.
The molecular mechanics calculations should provide
The results described here, together with our previous
some insight into the reasons for the failure of the N8 and N7 observations on the folding of AD 2-mers, indicate that the
backbones, but the structures in Fig. 5 are rather complicated. choice of backbone is critical to the successful development of
Further experimental information was obtained from X-ray synthetic information molecules designed to form H-bonded
crystallography. Single crystals suitable for X-ray analysis were duplexes between complementary recognition sites. If the
obtained for the phosphine oxide 2-mer with the N8 backbone. backbone is very flexible (C9), duplex formation will always be
Fig. 6 compares the backbone conformation in the solid state favourable for homo-sequence oligomers, but intramolecular
with the conformations of the 2-mer and 3-mer backbones interactions will complete with duplex formation in mixed
from the energy minimum molecular mechanics structures of sequence oligomers. The solution is to use a more rigid back-
the duplexes shown in Fig. 4 and 5.
bone, but as the results here show, this approach carries the
The X-ray and the molecular mechanics structures of the risk that the conformational states accessible to the backbone
2-mer are very similar: the two recognition modules are may not be compatible with duplex formation. We have
oriented in an anti arrangement, and this motif is repeated in studied three isomeric backbones (C8, N7 and N8) that are a
the 3-mer molecular mechanics structure. The X-ray structure semi-flexible combination of an aromatic ring and two methyl-
indicates that the molecular mechanics calculations provide a ene groups. One of these systems forms stable duplexes and
reasonable description of the conformational properties of the other two do not. Conformational analysis using molecular
these molecules. Moreover, the results suggest a reason why modelling is consistent with the experimental properties of
the N8 backbone does not make an extended multiply these systems and should provide a useful tool for future back-
H-bonded duplex. Duplex formation requires a syn arrange- bone design.
ment of the recognition modules with all of the interaction
sites pointing in the same direction, but the structures in
Fig. 6 imply that the N8 backbone prefers to adopt an alternat- Conflicts of interest
ing anti arrangement of recognition modules along the chain.
There are no conflicts to declare.
Conclusions
Acknowledgements
The conformational flexibility of the backbone plays an impor-
tant role in determining the ability of complementary
H-bonding oligomers to form a fully bound duplex. For a rela-
tively rigid backbone that has conformational properties com-
We thank the EPSRC and ERC for funding. We thank Mr Harry
Adams (University of Sheffield) for help with X-ray crystallo-
graphic data collection and analysis.
patible with duplex formation (e.g. C8), the stability of the
duplex increases uniformly with the number of recognition
sites present in the oligomers. For the C8 systems, the effective
Notes and references
molarity for formation of the first intramolecular H-bond, i.e.
duplex initiation (EM1), and the effective molarities for sub-
sequent intramolecular interactions that lead to zipping up of
the duplex, i.e. duplex propagation (EM2, EM3 etc.), have
similar values (Fig. 7a). The same is true for highly flexible
backbones (e.g. C9) that will always be able to find confor-
mations compatible with a fully bound duplex (Fig. 7b).
The other two backbones described in this paper (N8 and
N7) have quite different properties. These oligomers have rela-
tively rigid backbones that appear to be incompatible with a
fully assembled duplex. The effective molarities for duplex
initiation (EM1) for both of these systems are similar to the
values found for the C8 and C9 backbones, but the effective
molarities for duplex propagation (EM2) are much lower. The
reason is that formation of a doubly H-bonded complex
imposes little conformational constraint on the backbone,
whereas formation of a triply H-bonded complex can only be
1 (a) J. D. Watson and F. H. Crick, Nature, 1953, 171, 964;
(b) R. R. Sinden, DNA Structure and Function, Academic
Press, 1994.
2 (a) A. Eschenmoser, Science, 1999, 284, 2118;
(b) S. A. Benner, Acc. Chem. Res., 2004, 37, 784;
(c) S. A. Benner, F. Chen, Z. Yang, P. L. Luisi and
C. Chiarabelli, in Chemical Synthetic Biology, John Wiley &
Sons, Ltd, Chichester, UK, 2011, p. 69; (d) S. A. Benner,
Biol. Theory, 2013, 8, 357; (e) C. Wilson and A. D. Keef,
Curr. Opin. Chem. Biol., 2006, 10, 607; (f) D. H. Appella,
Curr. Opin. Chem. Biol., 2009, 13, 687; (g) E. T. Kool, Curr.
Opin. Chem. Biol., 2000, 4, 602.
3 Base modification of nucleic acids: (a) J. A. Piccirilli,
T. Krauch, S. E. Moroney and S. A. Benner, Nature, 1990,
343, 33; (b) Z. Yang, D. Hutter, P. Sheng, A. M. Sismour and
S. A. Benner, Nucleic Acids Res., 2006, 34, 6095;
(c) F. Wojciechowski and C. J. Leumann, Chem. Soc. Rev.,
2011, 40, 5669; (d) S. A. Benner, Curr. Opin. Chem. Biol.,
2012, 16, 581; (e) H. Liu, J. Gao, S. R. Lynch, Y. D. Saito,
L. Maynard and E. T. Kool, Science, 2003, 302, 868;
achieved within
a much more restricted conformational
window. As a result, the N7 and N8 backbones are not compa-
tible with the formation of an extended multiply H-bonded
This journal is © The Royal Society of Chemistry 2018
Org. Biomol. Chem.

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(f) E. T. Kool, Acc. Chem. Res., 2002, 35, 936; (g) E. T. Kool,
Rapid Commun., 2011, 32, 136; (d) H. Yamada, Y. Furusho,
H. Ito and E. Yashima, Chem. Commun., 2010, 46, 3487.
9 (a) J. Sánchez-Quesada, C. Seel, P. Prados, J. de Mendoza,
I. Dalcol and E. Giralt, J. Am. Chem. Soc., 1996, 118, 277;
(b) A. P. Bisson, F. J. Carver, D. S. Eggleston,
R. C. Haltiwanger, C. A. Hunter, D. L. Livingstone,
J. F. McCabe, C. Rotger and A. E. Rowan, J. Am. Chem. Soc.,
2000, 122, 8856; (c) A. P. Bisson and C. A. Hunter, Chem.
Commun., 1996, 1723; (d) B. Gong, Y. Yan, H. Zeng,
E. Skrzypczak-Jankunn, Y. W. Kim, J. Zhu and H. Ickes,
J. Am. Chem. Soc., 1999, 121, 5607; (e) B. Gong, Synlett,
2001, 582; (f) H. Zeng, R. S. Miller, R. A. Flowers and
B. Gong, J. Am. Chem. Soc., 2000, 122, 2635; (g) H. Zeng,
H. Ickes, R. A. Flowers and B. Gong, J. Org. Chem., 2001, 66,
3574; (h) B. Gong, Polym. Int., 2007, 56, 436; (i) B. Gong,
Acc. Chem. Res., 2012, 45, 2077; ( j) Y. Yang, Z.-Y. Yang,
Y.-P. Yi, J.-F. Xiang, C.-F. Chen, L.-J. Wan and Z.-G. Shuai,
J. Org. Chem., 2007, 72, 4936; (k) W.-J. Chu, Y. Yang and
C.-F. Chen, Org. Lett., 2010, 12, 3156; (l) W.-J. Chu, J. Chen,
C.-F. Chen, Y. Yang and Z. Shuai, J. Org. Chem., 2012, 77,
7815; (m) E. A. Archer and M. J. Krische, J. Am. Chem. Soc.,
2002, 124, 5074; (n) H. Gong and M. J. Krische, J. Am.
Chem. Soc., 2005, 127, 1719.
H. Lu, S. J. Kim, S. Tan, J. N. Wilson, J. Gao and H. Liu,
Nucleic Acids Symp. Ser., 2006, 50, 15; (h) J. N. Wilson and
E. T. Kool, Org. Biomol. Chem., 2006, 4, 4265.
4 Phosphate modifications of nucleic acids: (a) S. A. Benner
and D. Hutter, Bioorg. Chem., 2002, 30, 62; (b) Z. Huang,
K. C. Schneider and S. A. Benner, J. Org. Chem., 1991, 56,
3869; (c) Z. Huang and S. A. Benner, J. Org. Chem., 2002,
67, 3996; (d) C. Richert, A. L. Roughton and S. A. Benner,
J. Am. Chem. Soc., 1996, 118, 4518; (e) P. Li, Z. A. Sergueeva,
M. Dobrikov and B. R. Shaw, Chem. Rev., 2007, 107, 4746;
(f) H. Isobe, T. Fujino, N. Yamazaki, M. Guillot-Nieckowski
and E. Nakamura, Org. Lett., 2008, 10, 3729;
(g) M. Eriksson and P. E. Nielsen, Rev. Biophys., 1996, 29,
369; (h) P. E. Nielsen, Chem. Biodiversity, 2010, 7, 786;
(i) P. E. Nielsen and M. Egholm, Curr. Issues Mol. Biol.,
1999, 1, 89; ( j) P. E. Nielsen and G. Haaima, Chem. Soc.
Rev., 1997, 26, 73; (k) Y. Ura, J. M. Beierle, L. J. Leman,
L. E. Orgel and M. R. Ghadiri, Science, 2009, 325, 73.
5 Sugar modifications of nucleic acids: (a) K. Schöning,
P. Scholz, S. Guntha, X. Wu, R. Krishnamurthy and
A. Eschenmoser, Science, 2000, 290, 1347; (b) A. van
Aerschot, I. Verheggen, C. Hendrix and P. Herdewijn,
Angew. Chem., Int. Ed. Engl., 1995, 34, 1338; 10 (a) A. E. Stross, G. Iadevaia and C. A. Hunter, Chem. Sci.,
(c) D. Renneberg and C. J. Leumann, J. Am. Chem. Soc.,
2002, 124, 5993; (d) D. A. Braasch and D. R. Corey, Chem.
Biol., 2001, 8, 1; (e) S. K. Singh, A. A. Koshkin and
J. Wengel, Chem. Commun., 1998, 455; (f) H. V. Nguyen,
Z. Y. Zhao, A. Sallustrau, S. L. Horswell, L. Male, A. Mulas
and J. H. R. Tucker, Chem. Commun., 2012, 48, 12165;
(g) L. Zhang, A. Peritz and E. Meggers, J. Am. Chem. Soc.,
2005, 127, 4174; (h) M. K. Schlegel, A. E. Peritz,
K. Kittigowittana, L. Zhang and E. Meggers, ChemBioChem,
2016, 7, 94; (b) G. Iadevaia, A. E. Stross, A. Neumann and
C. A. Hunter, Chem. Sci., 2016, 7, 1760; (c) A. E. Stross,
G. Iadevaia and C. A. Hunter, Chem. Sci., 2016, 7, 5686;
(d) D. Nűñez-Villanueva and C. A. Hunter, Chem. Sci., 2017,
8, 206; (e) D. Núñez-Villanueva, G. Iadevaia, A. E. Stross,
M. A. Jinks, J. A. Swain and C. A. Hunter, J. Am. Chem. Soc.,
2017, 139, 6654; (f) E. Stross, G. Iadevaia, D. Núñez-
Villanueva and C. A. Hunter, J. Am. Chem. Soc., 2017, 139,
12655.
2007, 8, 927; (i) P. Karri, V. Punna, K. Kim and 11 Although all of the interactions in these systems are strictly
R. Krishnamurthy, Angew. Chem., Int. Ed., 2013, 52, 5840.
6 (a) R. Kramer, J.-M. Lehn and A. Marquis-Rigault, Proc.
Natl. Acad. Sci. U. S. A., 1993, 90, 5394; (b) A. Marquis,
V. Smith, J. Harrowfield, J.-M. Lehn, H. Herschbach,
intermolecular interactions, we will use the term intra-
molecular to describe H-bonds that are formed after the
first intermolecular H-bond has brought the two molecules
together to form a complex.
R. Sanvito, E. Leize-Wagner and A. van Dorsselaer, Chem. – 12 (a) C. A. Hunter and H. L. Anderson, Angew. Chem., Int. Ed.,
Eur. J., 2006, 12, 5632; (c) H. L. Anderson, Inorg. Chem.,
1994, 33, 972; (d) P. N. Taylor and H. L. Anderson, J. Am.
Chem. Soc., 1999, 121, 11538.
2009, 48, 7488; (b) H. J. Hogben, J. K. Sprae, M. Hoffmann,
M. Pawlicki and H. L. Anderson, J. Am. Chem. Soc., 2011,
133, 20962.
7 (a) V. Berl, I. Huc, R. G. Khoury, M. J. Krische and 13 C. Xue and F.-T. Luo, J. Org. Chem., 2003, 68, 4417.
J.-M. Lehn, Nature, 2000, 407, 720; (b) V. Berl, I. Huc, 14 (a) U. Mayer, V. Gutmann and W. Gerger, Monatsh. Chem.,
R. G. Khoury and J.-M. Lehn, Chem. – Eur. J., 2001, 7, 2810.
8 (a) Y. Tanaka, H. Katagiri, Y. Furusho and E. Yashima,
Angew. Chem., Int. Ed., 2005, 117, 3935; (b) H. Ito,
1975, 106, 1235; (b) U. Mayer, W. Gerger and V. Gutmann,
Monatsh. Chem., 1977, 108, 489; (c) V. Gutmann, Pure Appl.
Chem., 1979, 51, 2197.
Y. Furusho, T. Hasegawa and E. Yashima, J. Am. Chem. Soc., 15 MacroModel, version 9.8, Schrödinger, LLC, New York, NY,
2008, 130, 14008; (c) Y. Furusho and E. Yashima, Macromol.
2014.
Org. Biomol. Chem.
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