Ruthenium-Based Sensors
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsPlease see attached PDF file.
Comments for author File: 
Comments.pdf
Written text is generally good quality.
Author Response
This is a valuable review that nicely summarizes the field of ruthenium-based sensors. It was
interesting to see the different strategies for binding various species, in particular, and this will be of
interest to researchers in other Ru-centric fields, such as metallopharmaceuticals. The review is
generally well written and suitable for publication in Inorganics with only minor revisions. These are
listed below, with some minor textual corrections indicated in the attached, annotated PDF.
Answer: Thank you, they have been corrected.
Abstract: “In the periodic table of the elements, ruthenium is ideally placed, right in the middle, just
above iron.” I’m not sure why being placed in the middle of the periodic table is ideal. There are many
excellent metal-based sensors from transition elements beyond the middle of the table. Also, Ru is
below iron (not above).
Answer: The abstract has been modified accordingly: ...ruthenium is occupying an excellent position, just below iron.
Introduction: It would be worth noting that most of the examples given are polypyridyl complexes
and describing the properties of these type of compounds that make this the cases (their
photophysical properties, with many corresponding biochemical applications). Similarly, the second
most common are Ru arene complexes. These are also widely studied for catalysis and anticancer
properties and their relevant literature should be noted.
Answer: The review was primarily focussing on analytes, and the electronic properties of the ruthenium complexes have been acknowledged in the following sections.
Line 44, 45: “Cu2+, a common pollutant in the environment (pesticides, fertilizers), which at high
concentrations can generate health issues”. This is not a good description of the health risks
associated with Cu, which are very low. Copper is a biometal that is largely considered non-toxic.
Indeed, examples of copper toxicity are very rare. It is still of interest to have sensors for Cu for
reasons related to metallomics, but not related to toxicity.
Answer: This section has been modified: a common pollutant in the environment (pesticides, fertilizers), but more importantly, an interesting biomarker in metallomics.
Line 60: Does the paramagnetism of the Cu2+ ion contribute to the quenching of the luminescence
compared to the other 2+ ions?
Answer: I don't know, and there was no clear answer to that in the related article.
Line 76: It is not immediately obvious how the ligand is “tetradentate”. Is it possibly tridentate?
Answer: Effectively, but according to the Authors they do have a tetradentate system, the four nitrogen atoms being part of the coordination. However, I agree that a tridentate coordination (involving less distortion) can not be excluded.
Throughout the first section: I could be valuable, where known, to show the coordination of the
second metal species (as in Figure 3). As above, it is sometimes unclear how the sensed metal ion
binds and what other ligands (e.g. H2O/OH) would be involved. In some cases,this may not have been
reported. However, it would be very valuable in several of the examples. This is particularly the case
for Figures 2, 4, and 5.
Answer: Figure 5 has been modified accordingly, adding the cation, however, for the other two, the binding mode in solution is not clear. They do have an X-ray structure with Hg2+, however, that doesn't mean that the same binding mode is observed in solution.
Figure 20: It could be worthwhile to show also the sulfate coordination (since it is mentioned in the
figure caption.
Answer: Done, the complexation to sulfate is now presented as well as carbonate.
Scheme 6: This figure is quite confusing. In particular, the RNA/DNA interactions are not clear from
the schematic
Answer: Scheme 6 has been redrawn, adding information to make it clearer.
Line 728: “limit of detection was determined to be at a N2 partial pressure of 0.01 MPa”. This seems
like low sensitivity (approximately 0.1 atm). Is this correct? Also, these are strange units; 10 kPa
would be better.
Answer: Yes, this is the value reporter by Prof. Ogo and his team !
Reviewer 2 Report
Comments and Suggestions for AuthorsIn this review, Therrien talked about the development of ruthenium-based sensors for the detection of various analytes, such as cations, anions, carbohydrates and biomolecules. He listed the chemical structural features of ruthenium complex for the detection of analytes. He also highlighted the detection limit of ruthenium based sensors for different analytes, especially for cations and anions. He also illustrated the design mechanism of different sensors. The work appears to be comprehensive, all references are well cited and the topic will receive wide interest by sensor and inorganics community, especially people working on ruthenium-based sensors. The review provides valuable insights into designing of inorganics sensors, offering implications for future studies and practical applications. However, I do have some questions/concerns that I think the authors should address before publication.
1. The first thing caught my attention in the abstract is, in the design of sensors, the use of ruthenium complexes remains scarce. Actually, this is not true. The ruthenium sensor were widely reported in the references in the last past 30 years.
2. There are more analytes that can be detected by ruthenium sensors, for example, nitric oxide. There are multiple references related to this study, https://doi.org/10.1002/chem.200903267 and https://doi.org/10.1002/chem.200903267. Another example is detection of thiophenol in living cells by ruthenium probes, https://pubs.acs.org/doi/10.1021/bc200506w.
3. The author listed the chemical structure of sensors he talked about in the review. But more importantly, more figures should be provided to illustrate how the probes work to yield signals for detection.
4. Another general problem of current manuscript is it only limit to ruthenium-based sensors. For a good review, the author should compare it with other sensors, what’s the pros and cons for ruthenium sensors. For example, for the detection of mercury ions, there are couple of other detection methods, such as organic dye and voltammetric sensors.
5. For the sensors of cations and anions, one important application is to detect analytes in the biological samples ranging from living cells to tissues.
6. The last but not least, I think the author should provide more mechanism about ruthenium based sensors, what make it so special, connecting the application to the property of ruthenium. And should also compare other cation based sensors.
7. For the future study, the following reference could provide more perspective. https://pubs.rsc.org/en/content/articlelanding/2015/cs/c4cs00391h/unauth
Author Response
The first thing caught my attention in the abstract is, in the design of sensors, the use of ruthenium complexes remains scarce. Actually, this is not true. The ruthenium sensor were widely reported in the references in the last past 30 years.
Answer: This sentence has been modified: However, in the design of sensors, the use of ruthenium complexes can be better exploited, as it possesses valuable electro- and photochemical properties.
There are more analytes that can be detected by ruthenium sensors, for example, nitric oxide. There are multiple references related to this study, https://doi.org/10.1002/chem.200903267 and https://doi.org/10.1002/chem.200903267. Another example is detection of thiophenol in living cells by ruthenium probes, https://pubs.acs.org/doi/10.1021/bc200506w.
Answer: Thank you for pointing out these references. These two references have been added to the manuscript, the first one in section 2.5 Gases (including a new Scheme and a full paragraph to describe the system), and the second one in section 2.4.4 Biothiols, with the analogous complex from the same group.
The author listed the chemical structure of sensors he talked about in the review. But more importantly, more figures should be provided to illustrate how the probes work to yield signals for detection.
Answer: This is an excellent suggestion, and we will keep that in mind for a future review. However, at the moment, we wanted to focus on the ruthenium complexes, not the mechanisms involved.
Another general problem of current manuscript is it only limit to ruthenium-based sensors. For a good review, the author should compare it with other sensors, what’s the pros and cons for ruthenium sensors. For example, for the detection of mercury ions, there are couple of other detection methods, such as organic dye and voltammetric sensors.
Answer: We are perflectly aware of that, but again, the focus was primarily on ruthenium complexes, coordination chemistry and accordingly chemosensors.
For the sensors of cations and anions, one important application is to detect analytes in the biological samples ranging from living cells to tissues.
Answer: We have emphasized that aspect when discussing the detection of nitric oxide, as well as in the conclusion.
The last but not least, I think the author should provide more mechanism about ruthenium based sensors, what make it so special, connecting the application to the property of ruthenium. And should also compare other cation based sensors.
Answer: Again, we can understand the deception of the Reviewer, however, we wanted to focus on the coordination chemistry, the structures, and the analytes. However, as stated before, that can be the subject of a nice review, focussing on mechanisms. Thank you for the suggestion.
For the future study, the following reference could provide more perspective. https://pubs.rsc.org/en/content/articlelanding/2015/cs/c4cs00391h/unauth
Answer: The reference has been added to the manuscript.
