Water Structures and Packing Efficiency in Methylene Blue Cyanometallate Salts

Round 1

Reviewer 1 Report

The manuscript ID: crystals-830839 report ‘’Water structures and packing efficiency in methylene blue cyanometallatesalts.’’ Four crystal structures were characterized by X-ray diffraction analysis. The water molecules and their hydrogen-bonding interactions with MB were discussed and supplemented with Hirshfeld surface analysis. Altogether, solid-state analysis is used to explain the hydration properties of (MB)･(cyanometallate) co-crystals. The work is interesting and as authors pointed out, the prediction of water molecules and their hydrogen bonding patterns is a complex process. Considering the importance of chloride salts of MB as cancer cell tracers in the medicine field, it is important to gather data in order to understand the polymorphs of MB solvate structures. I have two questions (1) why cyanometallates counter anions? Why not F, Cl, Br, and I? I strongly recommend authors should justify this in the introduction section. (2) What were the authors long-term goal with this project? Without answering these two points, this structural works seems like ''gifts'' of the main ongoing project. Otherwise, the work is well-designed and contains a well-written text. Therefore, I recommend the work for publication in the journal Crystals after the comments were addressed.

Author Response

Dear Reviewer, 

Thank you for reviewing our work. We are glad to have received your positive evaluation and we considered the points you expressed to improve our manuscript.

(1) why cyanometallates counter anions? Why not F, Cl, Br, and I? I strongly recommend authors should justify this in the introduction section.

This point is indeed not explicitly mentioned in the introduction. We added a sentence to fill this gap, which you can find below highlighted in bold in its context:

"Aiming to conduct such investigation on the crystallisation processes of methylene blue salts, we synthesized a series of four methylene blue cyanometallate phases using anions with different charges and geometries, and in the presence of water traces in the crystallisation media (non-anhydrous organic solvents). The choice of these class of metal complexes allowed us to selectively varying the geometric and charge features of the anionic moieties, while maintaining unaltered the type of chemical groups that they contribute with to the overall supramolecular network. For each phase, the overall packing features are scrutinised [...]"

(2) What were the authors long-term goal with this project?

While we mention in the introduction that the present work addressed specifically the challenge to understand the link between packing and water molecules in methylene blue phases, we did not comment on the larger context of this work. Our general aim is to employ methylene blue as test molecule to see its many packing behaviours, which may be influenced by the geometrical or chemical features of solvents or anions, and therefore highlight some trends that can be extended in a more general crystal engineering context. We believe that methylene blue is an interesting system because of its pharmaceutical importance and its unique combination of rigidity, charge and its capability of performing highly efficient aromatic stacking, hydrogen bond interactions both as acceptor and donor, and even metal coordination as we previously proved (ref. 9 in the manuscript). Our general aim is deliberately broad and the study we presented condenses it in a much more narrow set of scientific questions.

We considered mentioning in the text our more general aim, but we concluded that this would poorly fit in the course of the text we follow in the intruduction. Moreover, as in your comments you did not express the advise to insert this information in the text, we would honestly prefer not to add it. In case you believe this would be a useful addition for the readers, we will obviously follow your advice and try to improve further our article.

With best regards

Reviewer 2 Report

Canossa and co-workers have submitted a great paper.  The changes in metal anion geometry and charges gave excellent insight into the role of packing efficiency and interaction requirements in these crystals of MB+ columns.  The four structures, coupled with the previous structures of the chloride and bisulfate, strongly support the conclusion of the ‘MB+ infinite stacking columns’ are ‘the main leading packing prerequisite’.  It is a delightful result. This paper fits wonderfully well in the scope and breadth of Crystals.  

A couple of awkward phrases could be fixed:

1. Page 4 ‘It is worth to highlight that the stacking columns… ‘  could be ‘It is worth highlighting that the stacking columns…’
2.  Page 5 ‘In facts, while in 2 each MB pair is surrounded…’ should read ‘In fact, while in 2 each MB pair is surrounded…’
3. Page 5 ‘As consequence, in the MB+ stacking column…’ could read ‘Consequently, in the MB+ stacking column…’
4. Page 10 ‘…better crystal packing is not always synonym of a higher occurrence…’ could be replaced with ‘…better crystal packing is not always synonymous of a higher occurrence…’
5. Page 10 ‘On the one hand, this difference originates also, and to a large extent, from the packing motif…’ could be replaced with ‘On the one hand, this difference also originates, to a large extent, from the packing motif…’
6. Page 10 ‘In facts, taking into simultaneous consideration packing efficacy and needs of specific types of interactions of the species involved…’ could be replaced with ‘In fact, taking into consideration both packing efficacy and the requirements of specific types of interactions of the species involved’

Author Response

Dear Reviewer, 

Thank you for reviewing our work. Needless to say, we are truly glad for your positive evaluation and grateful for the corrections you advised on the language side. We updated our manuscript accordingly.

Best regards

Reviewer 3 Report

The paper reported by Stefano Canossa, Claudia Graiff and co-worker titled "Water structures and packing efficiency in methylene blue cyanometallate salts" describes the structure of four methylene blue cyanometallate phases and the influence of various  anions in  the packing, depending of the shape and charge the anions lead to the formation of differently hydrated structures. They also describe that water molecules play various roles as isolated fillings, dimers, or also the formation of an infinite network

The paper is well referenced and well written, the results are relevant and interesting and overall they are supported by the experimental data obtained. All the compound are very well characterized and relevant X-ray structures are also described and therefore I am very pleased to recommend this paper for publication in Crystals.

Author Response

Dear Reviewer, 

Thank you for reviewing our work. We are truly glad to have received your positive evaluation.

Best wishes