4.1
Final publishable summary report
An executive summary (not exceeding 1 page)
In summary, the formation mechanism of the host-guest complex is dominated not
only by conformational restrictions but also by solvation dynamics. In chloroform, all
guests 2a-2d and 3 with one linear chain end form the complexes too fast to be
determined, because the terminal chain of 2a-2d and 3 presenting a stretchable state is
an open end, resulting in their formation of host-guest complexes through threading
mechanism. In chloroform‒acetone mixtures, the terminal chain of 2a-2d and 3
beginning folding and entanglement becomes a blocked end, resulting in the
formation process of the host-guest complexes changing from dominantly threading to
winding model. This is due to the fact that the chain end of guests is entangled more
seriously with increasing the volume proportion of polar solvents (acetone). In
chloroform‒acetonitrile mixtures, the change of molecular conformation and process
for forming complex are similar to that in chloroform‒acetone mixtures, but the
solvation effect of acetonitrile is much stronger than that of acetone on the
entanglement of the terminal chain, resulting in the more seriously decrease of their
complexation rate compared with that in chloroform‒acetone mixtures. Furthermore,
for 2a with short chain length and 3 with oligoethyleneglycol group, both
complexation rate are too fast to be determined even in 10% acetone in chloroform
(vol/vol) compared with 2b-2d, because the terminal chains of 2a and 3 are more
extended than that of 2b-2d whether in chloroform‒acetone mixtures or in
chloroform‒acetonitrile ones. Correspondingly, the formation mechanism of
15mer2a or 3 tends to dominantly threading process compared with that of
15mer2b, 2c or 2d.
A summary description of project context and objectives (not exceeding 4 pages)
In
a
previous
1
paper ,
we
reported that a
rod-shaped guest
incorporating five
methylene
units
can match the
helix length of
15mer well. The
guest with stopper
may prevent itself
from
threading
into the helix
cavity but allow a single helix to wind itself. However, the guest without bulky end
groups forms a complex probably by a simply threading of the guest into the helix
cavity. In order to obtain more information about the mechanisms, we investigate in
detail on the winding or threading kinetics during the formation of the host-guest 1:1
complexes between 15mer and rod-shaped guests 1-3 (Fig. 1) in different solvents.
Thus, we designed and synthesized a series of rod-shaped guests containing linear
chains of different lengths from 4 to 20 atoms (2a to 2d, 3) at one end and bulky
group at the other. We expected that the linear chains of the guests could be tuned
from a linear state to an aggregated state by varying the polarity of environment.
Since one end of the guest molecule is blocked by the bulky terminal, the guest can
only be threaded into the helix cavity through the open long chain end under certain
conditions. In this case, threading mechanism is expected for the formation of the
host-guest 1:1 complexes between 15mer and rod-shaped guests. Otherwise, winding
mechanism is expected. Reference compound 1 containing bulking groups at both end
was synthesized, which can only form the complex through winding mechanism.
Their 1H nuclear magnetic resonance (NMR) investigations were carried out in
chloroform, chloroform‒acetone and chloroform‒acetonitrile mixtures, respectively.
The host-guest 1:1 complexes between 15mer and rod-shaped guests form readily at
25°C. We have known that the aromatic amide oligomer 15mer folds into
single-helical
conformer,
which
then
aggregates to
form
double-helical
duplex (Figure
2)1.
The
formation of
host-guest
complexes
arises from a single helix wound around a rod-shaped guest. The pure single-helical
conformer of 15mer could be isolated by selective precipitation from methanol even
though it constitutes a minor component in solution. Upon dissolving it again in
CDCl3, in the presence of a rod-shaped guest, the complex between the helix host and
the linear guest forms first at 25°C, accompanying very slow formation of the double
helix which could be negligible when estimating the rate constant of host-guest
complex formation. The kinetics of host-guest complex formation follows second
order kinetics well when the proportion of formed complex is less than 50%. To study
the kinetics of 15mer on 1-3, equimolar amounts (2 mM) of a rod-shaped guest and
compound 15mer were mixed and the change of the 1H nuclear magnetic resonance
(NMR) spectrum as a function of time was measured, which is further to investigate
the effect of molecular conformational restriction and solvation on the formation
mechanism of helix-rod host-guest complexes.
A description of the main S&T results/foregrounds (not exceeding 25 pages)
The calculated rate constants (k) in different solvents, namely, chloroform,
chloroform‒acetone mixtures, and chloroform‒acetonitrile mixtures, are presented in
Table 1. From the perspective of conformation of guest molecules, for 1 with
stoppers at both ends, the rate constants of formation of 15mer1 are much lower
than those of other guests with one open alkyl or oligoethyleneglycol chain end under
same conditions. In the series of guests containing alkyl chains, the rate constant of 2a
with four atoms length end is faster than that of others with longer length end (2b-2d).
When the number of carbon atoms of the terminal alkyl chain is equal to or larger
than eight, the rate constants of formation of 15merguests are similar. It is evident
that their mechanism of host-guest complexes formation varies with their
conformation change of both ends of guests. 1 with blocked ends forms the host-guest
complex mainly by winding mechanism resulting in a slow complexation rate. From
2a to 2d, the length is longer and longer, and the chain is entangled more and more
easily. Thus, the open alkyl chain end is transferred to the blocked end, and the
folding chain affecting the complexation rate. If the steric hindrance arising from
entanglement of the terminal chain is large enough to prevent itself from threading
into the cavity of the helix host, the winding mechanism of host-guest complexes
formation will be advantageous. The analysis of data indicated that the effects of
steric hindrance for the terminal alkyl chain with eight or larger than eight atoms on
formation of host-guest complex are similar and their complexation rates tend to be
constant. Thus, the mechanism of host-guest complexes formation for 2b-2d is not
only threading model but also accompanying winding model, but that for 2a is
dominantly threading model. From the perspective of polarity of solvents, no matter
how the conformation of both the chain ends changes, the complexation rate constant
decreases with the increase of the volume proportion of acetone or acetonitrile in the
mixed solvents (see Fig. 3). Moreover, the complexation rate constant in
chloroform‒acetonitrile mixtures decreases more quickly than that in
chloroform‒acetone mixtures, probably because the polarity of acetonitrile is stronger
than that of acetone. It showed that the host-guest complexing process is dominated
not only by conformational restrictions but also by solvation dynamics. Chloroform is
non-polar solvent, and acetone and acetonitrile are polar aprotic solvent. On one hand,
about the rod-shaped guest, with increasing the polarity of solvents system, one
terminal chain will aggregate and be entangled more and more seriously resulting in
mainly winding process to form host-guest complex. Compared 3 with 2c, even the
length of 3 (with nineteen atoms chain end) is analogous to 2c (with twenty atoms
chain end), the complexation rate constant of 3 is higher than that of 2c. According to
the principle that like dissolve like, the more polar oligoethyleneglycol chain in the
chloroform‒acetone or chloroform‒acetonitrile mixtures is likely to adopt a more
extended conformation than the less polar alkyl chain. Thus, the probability of
adopting the threading process for 3 is much higher than that for 2c. On the other
hand, for the helix host, previous studies have shown that an extreme conformation
stability of helical aromatic oligoamides is present in methanol‒water mixtures2. The
polarity of acetonitrile is analogous to methanol (their polarity index is around 6)3, so
it could be deduced that the conformation stability of the single helix is enhanced in
chloroform‒acetonitrile mixtures due to the introducing of acetonitrile into mixed
solvents system. In the same way, on account of introducing acetone increasing
polarity of solvents system, it will also enhance the conformation stability of the host
single helix molecules to a certain extend. Seeing from 1H NMR spectra showing the
formation of host-guest complexes (Fig. 4), it is obvious that there are little peaks of
duplexes appearing in chloroform‒acetone and chloroform‒acetonitrile mixtures to
confirm the single helix stability in those solvents further. When the single helix
conformation is more and more stable, the host molecule wind around a rod-shaped
guest more and more difficultly. Furthermore, the polar solvents could probably
restrain interaction between the host and guest molecules, which could be another
reason for a decrease of the complexation rate with the polarity of solvents increasing.
As shown in Fig. 5, due to introducing the stronger polar solvent and the higher
proportion of polar solvent, the host-guest complex forms much less. For example, the
content of complex 15mer3 is less than 60% when it approaches equilibrium in
10% acetonitrile / chloroform (vol/vol).
CDCl3
CDCl3:Acetone=9:1
CDCl3:Acetone=4:1
CDCl3:Acetone=1:1
CDCl3:CD3CN=49:1
CDCl3:CD3CN=19:1
CDCl3:CD3CN=9:1
100
% of complex
80
60
40
100
80
60
CDCl3
CDCl3:Acetone=9:1
CDCl3:Acetone=4:1
CDCl3:Acetone=1:1
CDCl3:Acetone=1:4
CDCl3:CD3CN=49:1
CDCl3:CD3CN=19:1
CDCl3:CD3CN=9:1
40
20
20
0
(b)
% of complex
(a)
0
2000
4000
6000
8000
time (s)
10000 12000
0
0
2000
4000
6000
time (s)
8000
10000
(d)
100
80
80
% of complex
100
% of complex
(c)
60
CDCl3
CDCl3:Acetone=9:1
CDCl3:Acetone=4:1
CDCl3:Acetone=1:1
CDCl3:Acetone=1:4
CDCl3:CD3CN=49:1
CDCl3:CD3CN=19:1
CDCl3:CD3CN=9:1
40
20
0
0
2000
4000
6000
8000
60
CDCl3
CDCl3:Acetone=9:1
CDCl3:Acetone=4:1
CDCl3:Acetone=1:1
CDCl3:Acetone=1:4
CDCl3:CD3CN=49:1
CDCl3:CD3CN=19:1
CDCl3:CD3CN=9:1
40
20
0
10000
0
2000
time (s)
4000
6000
8000
10000
time (s)
Figure 5. Time traces of the formation of complexes 15mer1 (a), 15mer2a (b),
15mer2c (c) and 15mer3 (d) from single stranded oligomer 15mer (2 mM) and 1 (2
mM), 2a (2 mM), 2c (2 mM) and 3 (2 mM), respectively, in CDCl3 monitored by 1H NMR at
25°C.
Table 1. The complexation rate constants (k) in different solvent systems.
xacetone†
Atoms
guest
CDCl3
(n)
1
2a
2b
2c
2d
3
xCD3CN‡
4
8
20
30
19
0.69
ND*
ND*
ND*
ND*
ND*
0.1
0.2
0.5
0.8
0.02
0.05
0.1
0.26
ND*
4.01
4.12
4.00
ND*
0.20
3.13
1.44
1.28
1.45
4.57
0.16
1.23
0.76
0.70
0.71
2.80
**
1.19
0.75
0.70
0.71
2.83
0.069
3.07
**
0.82
**
5.46
0.031
1.27
**
0.28
**
1.38
0.015
0.42
**
0.14
**
0.61
† xacetone is acetone volume fraction.
‡ xCD3CN is acetonitrile volume fraction.
* Too fast to be determined.
** Not measured.
In conclusion, the formation mechanism of the host-guest complex is dominated not
only by conformational restrictions but also by solvation dynamics. To figure out the
dynamic assembly process of this type of helix-rod host-guest complexes is a key to
design nanomachines or molecular motor and to explore biological processes.
References
1. Quan Gan, Yann Ferrand, Chunyan Bao, Brice Kauffmann, Axelle Grélard, Hua
Jiang and Ivan Huc, Science, 2011, 331, 1172−1175.
2. Ting Qi, Victor Maurizot, Hiroki Noguchi, Thiraporn Charoenraks, Brice
Kauffmann, Makoto Takafuji, Hirotaka Ihara and Ivan Huc*, Chem. Commun. 2012,
48(51), 6337−6339.
3. C. Reichardt, Chem. Rev. 1994, 94, 2319−2358.
The potential impact (including the socio-economic impact and the wider societal
implications of the project so far) and the main dissemination activities and
exploitation of results (not exceeding 10 pages)
Introducing different linear length chain at one end to tune the conformation of the
rod-shaped guest by changes of solvent polarity, we expect to observe the change of
kinetics from threading to winding process for forming helix-rod host-guest
complexes. The more insight into the mechanism of complexes formation will be
concluded. To figure out the dynamic assembly process of this type of helix-rod
host-guest complexes is a key to design nanomachines or molecular motor and to
explore biological processes.
The project serves the objective of creating long term collaborations between Europe
and the third country. The foldamer research is expected to keep developing rapidly in
the coming years and there are enough active European and Chinese groups to
establish strong networking. The return phase is an efficient opportunity to initiate the
collaborative development of tunable molecular devices. The coupling of monomeric
units developed by our group to those developed by the European host allow a huge
modularity of the oligomeric system and therefore of the expected physical properties.
The one year collaboration in the return phase of this project explored the potential of
combining monomeric units of different nature and to extract guidelines for the
rational design of helically folded molecular devices. Moreover, the project itself has
a great potential for further developments and deeper theoretical and experimental
investigations, providing the ground for long term collaborations.
The fields of foldamers and molecular assembly are considered to be highly important
areas of research by the scientific community, as illustrated by (1) the high level of
funding of these areas in competitor countries such as Japan or USA; and (2) the high
number of publications in these areas in major chemistry journals, in particular by the
groups involved in this project, and including one paper published in Science in 2011.
The project proposes important a highly system approach with high chances of
success will very likely contribute to Europe’s competitiveness in these areas.
The researcher Ting Qi got an associate professor position in University of Chinese
Academy of Sciences (UCAS) this summer just after her return phase.
The address of the project public website, if applicable as well as relevant contact
details
No.