Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations
Round 1
Reviewer 1 Report
The manuscript investigated the complexation of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) with β-cy-11 clodextrin (β-CD) in 1:1 and 2:1 host-guest molecular ratio using molecular docking and M062X/6-31G(d,p) calculations, to identify the fitting parameters which can indicate the stability of the molecular fits in complex formation of each stoichiometry host-guest ratio. This is an important study which can accelerate the application of CBD and THC in pharmaceutical disciplines. The manuscript has been written very well. The figures support the overall conclusions of the study. Only two small suggestions are listed below. Firstly, the writing tense of the full text needs to be unified. The past tense is recommended for completed research. Secondly, I suggest authors to provide the important findings and significance of this study in Abstract Part.
Author Response
Response to Reviewer 1 Comments
The manuscript investigated the complexation of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) with β-cyclodextrin (β-CD) in 1:1 and 2:1 host-guest molecular ratio using molecular docking and M062X/6-31G(d,p) calculations, to identify the fitting parameters which can indicate the stability of the molecular fits in complex formation of each stoichiometry host-guest ratio. This is an important study which can accelerate the application of CBD and THC in pharmaceutical disciplines. The manuscript has been written very well. The figures support the overall conclusions of the study.
Author response: We would like to thank the referee for taking the time to review our manuscript.
Only two small suggestions are listed below. Firstly, the writing tense of the full text needs to be unified. The past tense is recommended for completed research.
Author response: Thank you for pointing this out. Accordingly, throughout the revised manuscript, the writing tense of the full text has been corrected.
Secondly, I suggest authors to provide the important findings and significance of this study in Abstract Part.
Author response: As suggested by the reviewer, we have added the important findings and significance of our study in the revised manuscript, Abstract Part [line no. 21-27, page 1].
Reviewer 2 Report
The manuscript entitled ‘Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations’ is well collated & informative. The author has compiled and written the sections nicely and discussed the outcomes critically. The manuscript can be accepted, however, few comments are needed to be addressed to improve the quality.
· Abstract: line 11: please rephrase for clarity
· Line 17: “Three dimerized of β-CDs structures” or “Three dimerized form of β-CDs”
· Pg 2: line 79: please spell out “HOMO” and “LUMO” in first appearance
· Pg 5: line 148-149: please abbreviate conformation I and II to “Conf.I” and “Conf. II” respectively
· Pg 6: line 184-185, please reframe the sentence for better understanding
· Pg 10, section 4.2: please cite a few references suitably in methodology
· In figure 2 and 3 caption, please check if 2(c) and 3(c) is conformation II is correct?
· Please check figure captions and make it in a uniform according to journal style.
· The font of some text in table headings/ body is not consistent.
For example, table 5 headings.
· Pg 10: please check heading levels. For example, after section 4.2, section 4.4 is placed. Please renumber
Author Response
Response to Reviewer 2 Comments
The manuscript entitled ‘Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations’ is well collated & informative. The author has compiled and written the sections nicely and discussed the outcomes critically. The manuscript can be accepted, however, few comments are needed to be addressed to improve the quality.
Author response: We would like to thank the referee for taking the time to review our manuscript.
Abstract: line 11: please rephrase for clarity
Author response: Thank you for pointing this out. The sentence has been rephase to be “The complexation of β-cyclodextrin (β-CD) with cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) was investigated using molecular docking and M062X/6-31G(d,p) calculations” in the revised manuscript [Page 1, line 11].
Line 17: “Three dimerized of β-CDs structures” or “Three dimerized form of β-CDs”
Author response: Abstract part has been updated, such that this sentence disappears. Accordingly, throughout the revised manuscript, the writing of this sentence has been corrected from “three dimerized of β-CDs structures” to be “three dimerized form of β-CDs” [Page 5, line 26-27].
Pg 2: line 79: please spell out “HOMO” and “LUMO” in first appearance
Author response: We have made the change. The new sentence reads as follows “…energy gap between HOMO (the highest occupied molecular orbital) and LUMO (the lowest unoccupied molecular orbital), …” [Page 2, line 36-38].
Pg 5: line 148-149: please abbreviate conformation I and II to “Conf.I” and “Conf. II” respectively
Author response: This observation is correct. We have changed “in both conformation I and II” to be “in both Conf. I and Conf. II” [Page 5, line 13].
Pg 6: line 184-185, please reframe the sentence for better understanding
Author response: We have changed “Where, the cyclohexene group of CBD located in β-CDTop during which its aliphatic chain located in β-CDBottom, as shown in Figure 5(a)-(c)” to be “In all of them, the cyclohexene group of CBD located in β-CDTop while its aliphatic chain located in β-CDBottom, as shown in Figure 5 (a)-(c).” [Page 7, line 2-4 ].
Pg 10, section 4.2: please cite a few references suitably in methodology
Author response: Thank you for pointing this out. We have cited a few references suitably in methodology [Page 10, line 19-20].
In figure 2 and 3 caption, please check if 2(c) and 3(c) is conformation II is correct?
Author response: We apologize if our original explanation of Conf. II did not clarify. We agree with the reviewer that further elaborating on this point using would be helpful. We added the following sentence to [Page 4, line 2-6], and hope that it is now clear: “The complex’s orientation, which the aliphatic chain of guest molecule located closer to the narrow rim, would be referred to as Conf. II. Note that, in the β-CD/THC Conf. II, the aliphatic chain of THC was puckered inside the cavity, as depicted in Figure 2(c), while in the β-CD/CBD Conf. II, the aliphatic chain of CBD elongated outside the cavity of β-CD (Figure 2(b)).”
Please check figure captions and make it in a uniform according to journal style.
Author response: Thank you for pointing this out. We have corrected the figure captions to be in a uniform according to journal style.
The font of some text in table headings/ body is not consistent. For example, table 5 headings.
Author response: Thank you for pointing this out. We have corrected the typo and made them consistent.
Pg 10: please check heading levels. For example, after section 4.2, section 4.4 is placed. Please renumber
Author response: We apologize for our error. We have renumbered the section 4.4 to be the section 4.3 [Page 10, line 22].
