Chirality Transfer in a Calixarene-Based Directional Pseudorotaxane Complex

Round 1

Reviewer 1 Report

In this paper, author investigated the pseudorotaxane complex with benzylammonium derivatives. They carried out DFT calculation, NMR study and optical rotation measurement to characterize the complex. Their research is interesting, but several arguments should be reconsidered before the publication.

 

In line 133, they proposes CH-π interaction as main interaction to form the endo-chiral form. However, it has been found that chloroform strongly interacts with phenyl group by CH-π interaction (Tsuzuki, S.; Fujii, A. Phys. Chem. Chem. Phys. 2008, 10, 2584-2594.). Thus, it is unlikely that the CH-π interaction is the main interaction to form the endo-chiral structure in CDCl₃ solvent. Furthermore, CH-π interaction originates in dispersion interaction and B3LYP/6-31G(2d,1p) level will underestimate the interaction. Other interaction could be the main interaction to govern the formation of endo-chiral structure.

 

About Figure 2, 2D and 1D NMR spectra is too small. Please enlarge the figure.

 

In line 276, the authors conclude that “the amplification of optical rotation comes from the ability of the acle to induce chiral conformation” but it is not only the answer and it could be exciton coupling of benzene rings of host and guest molecules that results in strong ORD signal. Author should clearly explain the possibility.

 

About Table 2, the symbol in second row, 1st column is unreadable. please check the format.

Author Response

Referee:

In line 133, they proposes CH-π interaction as main interaction to form the endo-chiral form. However, it has been found that chloroform strongly interacts with phenyl group by CH-π interaction (Tsuzuki, S.; Fujii, A. Phys. Chem. Chem. Phys. 2008, 10, 2584-2594.). Thus, it is unlikely that the CH-π interaction is the main interaction to form the endo-chiral structure in CDCl₃ solvent. Furthermore, CH-π interaction originates in dispersion interaction and B3LYP/6-31G(2d,1p) level will underestimate the interaction. Other interaction could be the main interaction to govern the formation of endo-chiral structure.

REPLY: DONE.

REPLY: DONE. We thank the referee for this suggestion. As reported in: Tsuzuki, S.; Fujii, A. Phys. Chem. Chem. Phys. 2008, 10, 2584-2594, the chloroform is  highly competitive solvent for pure CH-π interactions. However,  in our case the complex is mainly stabilized by strong H-bonding N-H....O^Calix interactions, which are strong enough to prevail with respect to CH-π interactions between calixarene aromatic cavity and CDCl₃ solvent. Of course, these H-bonding interactions are present both in endo- and exo-chiral forms giving a very similar stabilization. Therefore, the main difference between these forms mainly comes from the additional CH-π interactions between CH-CH₃ group of the ammonium axle and the calixarene cavity that stabilize more the endo-chiral stereoisomer, as corroborated by NBO calculations. 

To make more clear this concept we have changed the pertinent text at pag 4 (rows 149-152) as follows: 

DFT calculations suggested that, in addition to the fundamental H-bonding N-H....O^Calix interactions, the a-methyl group establishes additional stabilizing secondary C‒H···π interactions with the aromatic walls which favor the preferential formation of the “endo-chiral” diastereoisomer.

Referee:

About Figure 2, 2D and 1D NMR spectra is too small. Please enlarge the figure.

Reply: DONE. The Figure was revised.

 

Referee:

In line 276, the authors conclude that “the amplification of optical rotation comes from the ability of the acle to induce chiral conformation” but it is not only the answer and it could be exciton coupling of benzene rings of host and guest molecules that results in strong ORD signal. Author should clearly explain the possibility.

 

REPLY: DONE "The reviewer is right. The amplification of the chiral response could well come from an excitonic mechanism, whereby occupied/excited orbitals of the host couple with excited/occupied orbitals of the guest. What Figure 6 shows is that in the system studied this contribution is minor and accounts for just a small fraction of the effect (the distance between the curves +-+ and *-*).  To better point out this, we have added these pieces of text:   p. 8,    Old sentence: <<This indicates that the main mechanism of amplification of optical rotation comes from the ability of the axle to induce a chiral conformation of the host. >>  -->     New sentence: <<This indicates that the main mechanism of amplification of optical rotation comes from the ability of the axle to induce a chiral conformation of the host. The mechanism of amplification of chirality through the interaction of occupied and virtual orbitals of different units (host and guest) accounts in this case only for a small fraction of the effect (quantifiable from the distance of the red-diamonds and magenta-asterisks curves in Fig. 5, right).>>   p. 10 : Old sentence: << This result suggests that the mechanism of amplification of optical rotation comes from a chirality transfer from the axle to the wheel mainly by inducing a chiral conformation of the host.>>   -->   New sentence: << This result suggests that the mechanism of amplification of optical rotation comes in our case from a chirality transfer from the axle to the wheel mainly by inducing a chiral conformation of the host, as also recently found for the VCD of a complex of a chiral ammonium salt with an achiral crown ether [10e].>>"    

Author Response File: Author Response.docx

Reviewer 2 Report

In this submitted manuscript, Dr. Neri and co-authors investigated the interesting phenomenon of “chirality transfer and amplification” from a linear chiral “axle” molecule to a macrocyclic achiral “wheel” component in the calixarene-based pseudo-rotaxane platform. In this study, it was found from both experimental results and DFT calculations that the endo-chiral pseudo-rotaxane stereoisomer is more preferred than the exo-chiral counterpart, proving the previously reported “endo-α-methyl-benzyl rule”.

This project is a nice follow-up to the authors’ previous work (Molecules, 2020, 25, 5323. Org. Lett., 2021, 23, 1804), and it is well-thought-out and completed. With sufficient experiments (1D and 2D NMR, optical rotation measurements), simulation studies (DFT calculations), and discussions, the manuscript is well organized and written in good quality to clarify the observations and conclusions. In terms of the manuscript content and importance, the work would appeal to the broad readership of Chemistry and I would recommend accepting it for publication after minor revisions.

1. Some of the abbreviations should be given the full name when they first appear, for example, line 43 “CD” and line 73 “ORD”, there was no complete name given to these two abbreviations in the whole manuscript.
2. The format of [B(ArF)₄]^- was not correct, as the negative charge was not properly superscripted or extra space was given. For example, line 49, 86, 118, 251, etc…
3. The mole of 2⁺·[B(ArF)₄]⁻ salt on line 86 should be double-checked, as it was given to be 1.9·10^-3 mmol. Should it be 1.9·10^-3 or 1.9·10^-6 mmol? The format of “×” should also be kept consistent, as in lines 85-86, both “·” and “×” were used.
4. A typo on line 90, CHCl₃ should be CDCl₃. On line 170, “atoms” should be “atom”.
5. The 2D COSY spectra in Figure 2 was in low resolution, and it is hard to read in some portion. Better to be replaced with a higher resolution NMR spectrum.
6. Part of the data in Table 2 was missed and needs to be fixed.

Author Response

Referee

1. Some of the abbreviations should be given the full name when they first appear, for example, line 43 “CD” and line 73 “ORD”, there was no complete name given to these two abbreviations in the whole manuscript. REPLY: DONE. The full name optical rotation has been given at pag 1, line 44 and optical rotatory dispersion (ORD) at pag 2. 
2. The format of [B(ArF)₄]^- was not correct, as the negative charge was not properly superscripted or extra space was given. For example, line 49, 86, 118, 251, etc… REPLY: DONE. [B(ArF)₄]^- was changed in [B(Ar^F)₄]^‒ everywhere.
3. The mole of 2⁺·[B(ArF)₄]⁻ salt on line 86 should be double-checked, as it was given to be 1.9·10^-3 mmol. Should it be 1.9·10^-3 or 1.9·10^-6 mmol? The format of “×” should also be kept consistent, as in lines 85-86, both “·” and “×” were used. REPLY: DONE.
4. A typo on line 90, CHCl₃ should be CDCl₃. On line 170, “atoms” should be “atom”. REPLY: DONE.
5. The 2D COSY spectra in Figure 2 was in low resolution, and it is hard to read in some portion. Better to be replaced with a higher resolution NMR spectrum. REPLY: DONE. The Figure has been revised.
6. Part of the data in Table 2 was missed and needs to be fixed. REPLY: DONE

Author Response File: Author Response.docx