Does Chlorine in CH₃Cl Behave as a Genuine Halogen Bond Donor?

Round 1

Reviewer 1 Report

As the title of the manuscript shows, this contribution is concerned with CH3Cl as a halogen bond donor, and whether or not the chlorine possesses a sigma-hole with a (partial) positive hole. A number of previous investigations have concluded that the sigma-hole on the chlorine in this molecule has a partially negative charge, which the authors of the present article argue is due to a combination of the theoretical method used and the isovalue "envelope" used in computing molecular electrostatic potentials. The authors then use a variety of theoretical techniques to attempt to show that polarization is less important in the intermolecular interactions of CH3Cl than previously claimed. There is an inherent interest in the underlying nature of intermolecular interactions when it comes to crystal engineering, and the somewhat controversial stance of the article gives it some extra potential interest for readers of Crystals. However, I am not entirely convinced by the authors' arguments and more work should be carried out to make a stronger case before the article is suitable for possible publication (further details below).

1) When comparing the nature of the sigma-hole, there are two main points of contention put forward in the argument. a) that the MP2/aVTZ method used by the current authors is better than the B3PW91/6-31G** used previously. b) that an isovalue of at least 0.001 a.u. should be used.

a) I'm not convinced that the method used in the present investigation is better than that used in the past. I recommend that the authors demonstrate more clearly that this is the case. At the least they should use the aug-cc-pV(T+d)Z basis for Cl (and other second row atoms), quadruple-zeta calculations should also be feasible. Why not use a more trustworthy method such as CCSD for the calculation of the electron density / electrostatic potential? Showing the results with a number of popular density functionals would also be useful.

b) As far as I can tell, the previous results used an isovalue of 0.001 a.u. (ref 18 and line 37 of present article). While it is interesting that changing the isovalue can lead to charge in the sign of the potential, it is no "smoking gun" in this case. This should be made clear to readers in the discussion.

2) On page 14, paragraph starting on line 412. Based on Table 1, I do not agree with the authors regarding most of the complexes being electrostatically driven. Edisp is clearly larger than Eeles + Eind for complexes (a), (c), (d), (e) and (i). In other cases the dispersion term is often larger or roughly equal to the contribution from electrostatics. I would contend that the results indicate most of these complexes are primarily dispersion bound.

More minor points

3) line 36. "Gaussian quality double/triple-zeta..." should be "double/triple-zeta quality Gaussian..."

4) Line 77. "ab" should be italicised.

5) Line 84. "Equilateral" is not correct here.

6) Line 146. "aug-pVDZ-JKFIT" should be "aug-cc-pVDZ-JKFIT". References to the papers describing the development of this and the RI fitting basis sets should also be included.

7) Line 392. The authors mention "DFT-SAPT", yet the Computational Details refer to regular (not DFT) SAPT. Which is correct?

Author Response

Answer to reviewer 1

As the title of the manuscript shows, this contribution is concerned with CH3Cl as a halogen bond donor, and whether or not the chlorine possesses a sigma-hole with a (partial) positive hole. A number of previous investigations have concluded that the sigma-hole on the chlorine in this molecule has a partially negative charge, which the authors of the present article argue is due to a combination of the theoretical method used and the isovalue "envelope" used in computing molecular electrostatic potentials. The authors then use a variety of theoretical techniques to attempt to show that polarization is less important in the intermolecular interactions of CH3Cl than previously claimed. There is an inherent interest in the underlying nature of intermolecular interactions when it comes to crystal engineering, and the somewhat controversial stance of the article gives it some extra potential interest for readers of Crystals. However, I am not entirely convinced by the authors' arguments and more work should be carried out to make a stronger case before the article is suitable for possible publication (further details below).

1) When comparing the nature of the sigma-hole, there are two main points of contention put forward in the argument. a) that the MP2/aVTZ method used by the current authors is better than the B3PW91/6-31G** used previously. b) that an isovalue of at least 0.001 a.u. should be used.

1. a) I'm not convinced that the method used in the present investigation is better than that used in the past. I recommend that the authors demonstrate more clearly that this is the case. At the least they should use the aug-cc-pV(T+d)Z basis for Cl (and other second row atoms), quadruple-zeta calculations should also be feasible. Why not use a more trustworthy method such as CCSD for the calculation of the electron density / electrostatic potential? Showing the results with a number of popular density functionals would also be useful.

Reply: Table 1 added, with results obtained using the methods suggested. This is given on page 6 

Based on the concern of a reviewer, and to confirm the reliability of [MP2/aug-cc-pVTZ] results above, we have examined the nature of the local most potentials on the Cl atom using the aug-cc-pV(T+d)Z basis set. We have used 10 different computational models, including the CCSD and nine popular density functionals. The results summarized in Table 1 demonstrate that the axial and lateral portions of the Cl atom on the C–Cl bond extensions are always positive and negative, respectively. Except for the PBE1 (PBE1PBE) functional, all other DFT and DFT-D3 functionals slightly underestimated the magnitude of V_S,max on Cl compared to that obtained with CCSD. In addition, both the H and C atoms along the C–H and Cl–C bond extensions are positive, indicating that these can be sites for hydrogen bond and chalcogen bond formation when placed in close proximity to negative sites on another molecule.

Table 1. 0.001 a.u. isodensity envelope mapped electrostatic potential on the outer surface of various bonded atoms in CH₃Cl, computed using various computational approaches in conjunction with the aug-cc-pV(T+d)Z basis set.

1. b) As far as I can tell, the previous results used an isovalue of 0.001 a.u. (ref 18 and line 37 of present article). While it is interesting that changing the isovalue can lead to charge in the sign of the potential, it is no "smoking gun" in this case. This should be made clear to readers in the discussion.

Reply: The discussion part addressing a)-b) is added on page ...

2) On page 14, paragraph starting on line 412. Based on Table 1, I do not agree with the authors regarding most of the complexes being electrostatically driven. Edisp is clearly larger than Eeles + Eind for complexes (a), (c), (d), (e) and (i). In other cases the dispersion term is often larger or roughly equal to the contribution from electrostatics. I would contend that the results indicate most of these complexes are primarily dispersion bound.

Reply: corrected.

More minor points

3) line 36. "Gaussian quality double/triple-zeta..." should be "double/triple-zeta quality Gaussian..."

Reply: corrected.

4) Line 77. "ab" should be italicised.

Reply: corrected.

5) Line 84. "Equilateral" is not correct here.

Reply: corrected.

6) Line 146. "aug-pVDZ-JKFIT" should be "aug-cc-pVDZ-JKFIT". References to the papers describing the development of this and the RI fitting basis sets should also be included.

Reply: Added.

7) Line 392. The authors mention "DFT-SAPT", yet the Computational Details refer to regular (not DFT) SAPT. Which is correct?

Reply: We have corrected this.

Reviewer 2 Report

The Manuscript ID: crystals-716538 report ‘’Does Chlorine in CH3Cl Behave as a Genuine Halogen Bond Donor?’’ The present study has shown that the analysis of the cps of the Laplacian of the charge density could be used to reveal the nature of the chlorine atom in CH3Cl upon contact with different Lewis basis. It is shown that the axial portion of the Cl has VS,max of +0.59 kcal mol-1 (a weak, s-hole), which is orthogonally encompassed by a negative belt (VS,min of –14.53 kcal mol-1). The charge density distributions at lateral and axial sites of Cl in CH3Cl is not isotropic suggesting the amphiphilic nature of the Cl atom is USEFUL information for organic reactions those performed in CH3Cl, particularly, geometries discussed in section 3.2. Authors also confirm the presence of interactions between the monomers in the complexes using QTAIM analysis. The manuscript would certainly benefit from linguistic improvements especially the section, introduction. I am a bit confused with lines 39-43. For example, ‘’……as is found when X = F in CF4 are indicative of….’’, where is X in the chemical formula or mentioned in the previous sentences? Please check. Overall, the study is an extensive and organized computationally investigation. Therefore, I recommend the article for publication in the journal crystal.

Author Response

The Manuscript ID: crystals-716538 report ‘’Does Chlorine in CH3Cl Behave as a Genuine Halogen Bond Donor?’’ The present study has shown that the analysis of the cps of the Laplacian of the charge density could be used to reveal the nature of the chlorine atom in CH3Cl upon contact with different Lewis basis. It is shown that the axial portion of the Cl has VS,max of +0.59 kcal mol-1 (a weak, s-hole), which is orthogonally encompassed by a negative belt (VS,min of –14.53 kcal mol-1). The charge density distributions at lateral and axial sites of Cl in CH3Cl is not isotropic suggesting the amphiphilic nature of the Cl atom is USEFUL information for organic reactions those performed in CH3Cl, particularly, geometries discussed in section 3.2. Authors also confirm the presence of interactions between the monomers in the complexes using QTAIM analysis. The manuscript would certainly benefit from linguistic improvements especially the section, introduction. I am a bit confused with lines 39-43. For example, ‘’……as is found when X = F in CF4 are indicative of….’’, where is X in the chemical formula or mentioned in the previous sentences? Please check. Overall, the study is an extensive and organized computationally investigation. Therefore, I recommend the article for publication in the journal crystal.

Reply: We thank the reviewer for recognizing the importance of our work. The text in the ms is modified as suggested. Whereas some parts of the paper (viz. ‘’……as is found when X = F in CF4 are indicative of….’’,) were taken from a previously published paper, we made it transparent during the revision.

Round 2

Reviewer 1 Report

The authors have responded to the referee comments in an appropriate way and addressed all of the concerns raised - making for a stronger manuscript.