Latonduine-1-Amino-Hydantoin Hybrid, Triazole-Fused Latonduine Schiff Bases and Their Metal Complexes: Synthesis, X-ray and Electron Diffraction, Molecular Docking Studies and Antiproliferative Activity
, Tim Gruene 1, Alexander Prado-Roller 1, Sandra Aranđelović 2, Jóhannes Reynisson 3 and Vladimir B. Arion 1,*Round 1
Reviewer 1 Report
Comments for author File: 
Comments.pdf
Author Response
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Author Response File: Author Response.pdf
Reviewer 2 Report
The paper submitted by Wittmann et al describes the synthesis, characterization, anticancer activity and docking calculations of a class of metal complexes containing the Latonduine-1-Amino-hydantoin Hybrid ligand.
The manuscript is very well written, very well organized and includes all the basic information that are necessary for publication (i.e. purity of the complexes, stability studies etc...). X-ray structure of some ligands and of one complex also reported that is always a great added value. The design of the ligand and the functionalization of the latter to include a moiety for the metal coordination is very smart and seems very promising. The biological analysis at the end is just a general screening on different cell lines and could be definitively improved with other essays (i.e. TK studies) but it is more than enough for Inorganics. The only think I would modify is to add the number of carbons (or at least C number 11) in Chart 2 so its allocation is immediate for the reader (without need going in the SI).
Author Response
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Author Response File: Author Response.pdf
Reviewer 3 Report
Crystal structure of compound 3 was determined by electron diffraction on crystals whose size makes them unsuitable for single crystal X-ray crystallography. The quality of crystal structure of 3 is significantly lower than that of B×MeOH and HL1×2DMF. Yet, there is no doubt that connectivity is determined and molecular structure is revealed. I am aware that the method is novel and that there are still a lot of challenges in how to perform experiments and process datasets of electron diffraction experiments. The low values of structural model quality indicators are discussed by the authors in the supplementary check CIF report.
When structural parameters (bond lengths, valence angles) of molecular structure of 3 are checked against CSD Mogul knowledge base, several high discrepancies are observed. Therefore, two questions come to my mind:
Is it reasonable to refine the structural model by using mean values of bond lengths obtained by CSD Mogul as target values for atom distances restraints (for those bond lengths that are behaving badly)?
Should this “bad” structural model be included in the CSD at all? Are we polluting database with low-precision structures? Several bond lengths deviate more than three sigma from the mean value found in Mogul for those particular structural fragments. I am aware that the amount of ED crystal structures published is low (compared to X-ray diffraction), but we should expect this to change in the future and some questions should be addressed from the start.
Some minor comments
Page 5, line 154: I propose to rename section “2.2. X-ray Diffraction and Electron Diffraction structures of species B, HL1 and 3” into “Crystal structure description of…” or “Molecular structure description of…”
Page 5, line 158: symbol for C2/c space group is wrongly typeset (2 should not be subscript)
Page 12, line 426: the inline equation is not formatted
Page 12, line 424: software used for crystal structure solution does not match the corresponding CIF entry (CIF line no 202)
SI, Page S5: Section “X-ray diffraction data” actually contain crystallographic data and refinement details of both X-ray diffraction and electron diffraction techniques.
Author Response
see file attached
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Thank you for the response. I do not have any other remarks of the manuscript.
Reviewer 3 Report
Authors have evaluated and addressed all my concerns. The updated refinement with inclusion of appropriate distance restraints resulted in model that shows less discrepancies from expected values of structural parameters. The manuscript has been sufficiently improved to warrant publication in Inorganics.
