Electrochemical Switching of First-Generation Donor-Acceptor Stenhouse Adducts (DASAs): An Alternative Stimulus for Triene Cyclisation

Round 1

Reviewer 1 Report

The present contribution by d´Allessandro, Beaves and their coworkers provides interesting insight into the capability of the photochemical DASA switch to undergo cyclisation also with an electrochemical trigger, namely oxidation. The efficiency of the electrogenerated response is often superior to that of the photochemical one, yet lacks the full degree of reversibility. Hence, the initial state is only partly recovered with time. The observations herein are interesting and are worthy of being communicated. However, this study in its present state leaves too many questions open to be published at this stage and requires some additional thought and work before resubmission.

First and foremost, oxidizing a neutral compound electrochemically (or chemically) means that it is converted to a cationic species. The product is, however, also neutral. So, where does the charge go? Of course it is well possible that the process is electrocatalytic. In this case, the oxidized form would isomerize, and this form, if associated with a higher redox potential, would then in turn oxidize further starting material. It might well be that the process indicated as Ox 2 is due to the oxidation of the isomerized product. An even more likely scenario could be as follows: Looking closely at the wave designated as Ox1, one notes that in every case there is an irreversible anodic shoulder superimposed on the main peak/wave assigned as Ox1, which is not accounted for in the author´s discussion. It is well possible that this shoulder belongs to the first oxidation of the open and what the authors assign as Ox1 then is the first oxidation of the cyclized product. This would be a likely appearance of the voltammetric response if cyclization in the oxidized state occurs very rapidly. This is easily probed by investigating, whether the addition of a very small, strongly substoichiometric amount of an oxidant to solutions of 1-6 does the trick. This needs to be clarified. If so, then the authors could even estimate the rate of the isomerization process from the ratios of peak currents for Ox1 and its prewave or, if the former holds, for Ox1 and Ox2.

Secondly, the assignment of process Red1 is easily misunderstood. Such naming would imply that it is the first reduction of the compounds 1-6, which is clearly not the case. Considering the potentials for P1 and P2, which lack the donor, it is obvious that the first reduction of compounds 1-6 is that which the authors denote as Red2. This means that feature Red1 must belong to the isomerized compound. This is easily probed by comparing with scans initiated in the opposite direction (i. e. reduction first). If so, one might then wonder whether reducing isomerized compounds 1-6 at a potential slightly negative of “Red1” will not trigger re-isomerization to the open form (this wave doesn´t look reversible).

Other, minor issues:

Page 1, Line 1 in paragraph 2: DASA should be defined on the first mentioning; line 4: respond (rather than have responded);

Page 2, line 4 from bottom: I recommend that the authors refer to Fig. 2d) when they talk about the cyclization to familiarize readers with the structures of the cyclized products.

Page 3, Legend to Fig. 2: in b), the authors should also indicate that the spectra were collected after applying a potential; line 3: rather than providing rather meaningless average values with three digits, the authors should provide potential ranges; paragraph 1, line 4 from bottom: Nernstian behaviour should be replaced by diffusion control; Ox 1 and Ox2 are both chemically not ideal processes.

Author Response

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Reviewer 2 Report

Reviewer comments

The article prepared by Shepherd et al. presents an alternative cyclization method of triene using electrochemical stimulus instead of the well-known and traditional photo-switching method. The experiments in the manuscript are well conducted and are very detailed even though the discussion could benefit from some more added elaborations. I believe the manuscript is important to the organic chemistry, analytical chemistry, and sensor community. So, it deserves publication if the authors could address the following minor comments and questions.

• The way figure 1 is arranged, it looks compounds 1,3, and 5 are synthesized from precursor P1 while compounds 2, 4, and 6 are synthesized from precursor P2. However, it is not clear why compound 5 is listed under precursor P1 and likewise why is compound 2 under precursor P2?
• As the authors noted, this process is at best a quasi-reversible process as revealed by the low quantum yield of the recovery of the linear isomer in figure 2c. I was interested to know how quantum yield of the recovery of the linear isomer in electrochemical switching compares with photo-switching. As the authors are presenting this method as an alternative to photo-switching, it would be essential to illuminate the reader by including a few lines about this comparison if there are known results from photo-switching of similar compounds in the literature.
• In figure 2c and in figures S45 to S49, is the thermodynamic recovery achieved by applying cathodic potential? I do not think this is clarified well. Also, in the manuscript in lines 88 through 90, there is a comparison for photo-switching and electrochemical switching are compared (87% vs 77%). Where are these data from? In table S2, the thermodynamic recovery for 6 is 83%?
• Compound 6, and to some extent compound 3, has very high recovery quantum yield. This could be very important in applications such as sensors. However, I did not see the authors address the near quantitative thermodynamic recovery observed in compound 6 in more detail, including the reasons why this compound shows such high recovery.
• It would be important to mention in the introduction that the cyclized zwitterions are the metastable states while the uncyclized are the initial states.

Minor typos

• In line 102, reference 19 font color is red?
• In line 109, I don’t know if it would be better to start the sentence by “ In summary” rather than “To summary”

Author Response

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Reviewer 3 Report

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Comments for author File: Comments.pdf

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Reviewer 4 Report

Decision: Accept after Minor corrections.
The authors show an electrochemical approach for the cyclization of donor-acceptor Stenhouse adducts (DASA). Electrochemical oxidation efficiently and controllably promotes cyclization, however, a poor recovery limits long-term function. The article is concise and well-written with all experimental evidence supporting the main conclusions with adequate supporting data. The manuscript can be directly published after addressing the following minor revisions (in no particular order).

• Page 3, Line 54. The recorded CVs actually show a peak or shoulder (as a function of scan rate) at around 0V indicating an initial oxidation step before the main oxidation Ox1 wave. Please describe the peak in the main text and ascribe its origin.
• Page 3, Line 66. Please provide the equations of the linear fits in the supporting figures (Fig. S39-S44) to show the obtained slope from experiments.
• Page 4, Line 88. “The main exception was 6 […]” Please expand/elaborate on why this is the case.
• Page 4, Line 105. Please propose/elaborate on possible strategies to overcome the current limitation and how to move the research forward.  

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Round 2

Reviewer 1 Report

The revision of the manuscript of d´Alessandro, Beaves and coworkers has, to my understanding, not resolved the major issues brought up by myself and by the other reviewers.

• There is still the issue about the electrochemical triggering of the cyclisation process. Prof. d`Alesandro, as an experienced electrochemist, will perfectly know that applying a potential to a neutral compound, which is obviously (or seemingly) positive of its first oxidation potential, will cause a bulk oxidation, i. e. generate its radical cation, but not an isomerized zwitterionic, yet still neutral compound, unless the process is electrocatalytic. In that case small amounts of charge will indeed suffice to trigger cyclization of the oxidized form. If the oxidation potential of the latter is positive of that of the initial open compound, it will then oxidize it and cause the next molecule to isomerize. None of that is, however, written in the manuscript. In the abstract, the authors even explicitly say that the isomerization happens after oxidation, that is in the oxidized (cationic) state.
• How does the potential applied to the SEC cell compare with the potentials in the CV experiment? The authors remain more than vague in this regard, only saying that there is a discrepancy (page 4)
• I also miss any electroanalytical characterization of the cyclized form, only data for the open ones are provided. Given the rather high yields, this should be an easy task to do. Knowledge of the electrochemical characteristics of these isomers would also aid in identifying their waves in the voltammograms, i. e. aid in proving or disproving an electrocatalytic mechanism. I guess that the cyclized form is also responsible for the wave denoted as Red1 as its forward peak seems to be absent in the initial scan. This is presently mentioned in an only very implicit manner of page 4, but should be made more clear.
• Page 3, “Red2 in 1-6 was consistent with redox processes associated with P1 and P2 precursors (ESI†, Fig. S37-S38 and Table S1) and were not attributed to the triene cyclisation.” This is impossible or at the very least very easily misunderstood. What the authors might wish to say is that the triene isomers showed reduction waves at similar potentials to those of the precursors, which is incompatible with a cyclized structure. This must be clarified
• The issue of how the photochemical and quantum yields were determined, which were raised by other reviewers, remains unanswered (Exp. procedures, how was the effective power output of the LEDs at the irradiation wavelength measured etc. I even do not fully grasp how the electrochemical efficiency was measured. Electrochemical efficiency is more than just the bleaching of the Vis band, it also has to take charge consumption on applying the potential into account.
• Does it really make sense to provide average values of redox potentials over two different families of compounds and two provide potentials with 4 digits (i. e. an accuracy of 0.5 mV)? I would really like to see how the authors manage to realize such precise measurements by CV.
• How do the closed isomers revert to their open forms? On thermal activation?

There are also several minor issues:

Page 1: Syntheses…. Involves (involve); in preparing orthogonal photo-switches and in photolithography etc.

To my level of understanding, the material cannot be published in its present state and needs thorough revision and improvement.

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