4.1Final 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 of2a-2d and 3 presenting a stretchable state is an open end, resulting in theirformation of host-guest complexes through threading mechanism. In chloroform‒acetone mixtures, the terminal chain of2a-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 of2b-2dwhether in chloroform‒acetone mixtures or in chloroform‒acetonitrile ones. Correspondingly, the formation mechanism of 15mer2a or 3 tends to dominantly threading process compared with that of 15mer2b, 2c or 2d.
A summary description of project context and objectives (not exceeding 4 pages)
In a previous paper1, 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 ofthe 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 1containing 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, for1with stoppers at both ends, the rate constants of formation of 15mer1 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 of2a 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 15merguests are similar. It is evident that their mechanism of host-guest complexes formation varies with their conformationchange 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 of2c. 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 arelittle 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 shownin 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 15mer3is less than 60% when it approaches equilibrium in 10% acetonitrile / chloroform (vol/vol).
Figure 5. Time traces of the formation of complexes 15mer1 (a), 15mer2a (b), 15mer2c (c) and 15mer3 (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.
guest / Atoms(n) / CDCl3 / xacetone† / xCD3CN‡
0.1 / 0.2 / 0.5 / 0.8 / 0.02 / 0.05 / 0.1
1 / - / 0.69 / 0.26 / 0.20 / 0.16 / ** / 0.069 / 0.031 / 0.015
2a / 4 / ND* / ND* / 3.13 / 1.23 / 1.19 / 3.07 / 1.27 / 0.42
2b / 8 / ND* / 4.01 / 1.44 / 0.76 / 0.75 / ** / ** / **
2c / 20 / ND* / 4.12 / 1.28 / 0.70 / 0.70 / 0.82 / 0.28 / 0.14
2d / 30 / ND* / 4.00 / 1.45 / 0.71 / 0.71 / ** / ** / **
3 / 19 / ND* / ND* / 4.57 / 2.80 / 2.83 / 5.46 / 1.38 / 0.61
†xacetoneis acetone volume fraction.
‡xCD3CNis 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 collaborationsbetween Europe and the third country.The foldamer research is expected to keep developing rapidly in the comingyears and there are enough active European andChinese groups to establish strong networking. The return phase is an efficient opportunity to initiate the collaborative development oftunable molecular devices. The coupling of monomeric units developed by our group to those developed by the European host allow a huge modularity of the oligomericsystem and therefore of the expected physical properties. The one year collaboration inthe return phase of this project explored the potential of combining monomeric unitsof different nature and to extract guidelines for the rational design of helically folded moleculardevices. Moreover, the project itself has a great potential for further developments and deepertheoretical and experimental investigations, providing the ground for long term collaborations.
The fields of foldamers and molecular assembly are considered to be highly important areas ofresearch by the scientific community, as illustrated by (1) the high level of funding of these areas incompetitor countries such as Japan or USA; and (2) the high number of publications in these areasin 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 likelycontribute 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
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