The Miracle of Vitamin B12 Biochemistry
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsDear Authors.
I must begin by commenting in a general way on the very good work done in the search and explanation of the history and biochemistry of vitamin B12 or cobalamin. An extensive and deep work of review and discussion of the ideas raised was done by the authors of this extensive review. The counterpoints made in the text, of putting the evidence and making a critical analysis are very well carried throughout the text.
The abstract summarizes the main ideas of the manuscript, describing and summarizing the manuscript. However, it focuses too much on the technicalities, moving away from the idea that emanates from reading the title.
The manuscript is difficult to follow, first because of the lack of a central idea that accompanies the reader to follow such a difficult development of the ideas, that an expert in biochemistry, can follow, but for a reader moderately knowledgeable of the subject, it makes him lose the idea that the authors try to develop in the different sections of the manuscript. The use of figures in the manuscript is underdeveloped by the authors, I do not know the reason why when reading the submitted document, there is a gap between the text and the figures, the reader must go back or advance more than 2-3 pages to see in the figures, what the text is mentioning. In my opinion, it is at this point, the figures, where the authors should work more deeply. First, the great majority of the figures are cut, not observing the totality of the reactions or the molecular structures of the molecular intermediates. Second, it would be very helpful if arrows or other signs could be used to indicate to the reader what is described in the text of the manuscript, which would help to improve the reading experience and to be able to observe what the authors are describing. Finally, the authors could begin the sections by indicating the central idea to be developed and conclude at the end of the section with the central idea or the main conclusions drawn from the development of the idea, since the length of each section makes the reader lose the thread of such an interesting topic. Another suggestion I make to the authors is to introduce the reader to the objective of each of the sections, to be able to follow the development of the biochemical and chemical mechanisms described in the manuscript.
In the references mentioned, they maintain a format of authors, title, journal in italics, and volume and pages. However, there is no uniformity in the references there are several without underlining, others in which some authors are underlined, in others all, in others the journal, the title. Please standardize, or if there is a meaning to these marks, explain it.
Finally, I would like to point out the enormous manuscript submitted, and that it deserves more prolixity in the figures and their use in the text, and the references. I hope that the authors will work on my comments, and send it again with a text and figures that allow the reader to follow such an interesting subject.
Author Response
Please see attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThe paper seems to be a quite useful review of an important problem of electronic structure and properties of important biological systems related to vitamin B12 and it analogs, which deserves publication in the journal “Reactions”. Of special importance in this review is the implication of the pseudo-Jahn-Teller effect (PJTE) as the background first-principle interaction that explains the origin of the basic feature of these and related systems.
Basically, the subject and the large volume of publications on the subject are well presented, except of the following incorrect interpretations and omitting that should be corrected before publication:
1. With regard to the history of the PJTE as an observable phenomenon, the author incorrectly cites some mathematical extensions of the two-level vibronic coupling problem, which were not related to observable properties. The first major physical problem solved as a observable PJTE was the revealing the origin of dipolar distortion leading to spontaneous polarizations and ferroelectricity (Bersuker, Physics Letters, 1966).
2. Similarly, a PJTE problem solving a biological problem, namely the mechanism of Hemoglobin oxygenation (Bersuker, Stavrov, Coord. Chem. Revs. 1988), which is indirectly related to the B12 problem, is also not mentioned by the author.
After these corrections the paper may be recommended for publication.
Author Response
Please see attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsDear Authors.
Thank you very much for insisting and sending again the manuscript with the suggestions, most of them answered. I find it excellent , help to read and to focus the ideas raised. Very good to order the figures according to the text, and to include in the text the figures used and shown.
The following seventeen figures are still cut or truncated in the version sent in PDF. They are Fig 6; 7; 8; 11; 13; 13; 16; 22; 24; 25; 27; 29; 30; 31; 32; 33; 34; 35.
I hope you can fix this problem before the publication of the manuscript.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe author introduced improvements to the text of the MS in accordance to my previous comments, the paper is ready for publication.
