Review Reports - Photoinduced Geometric Isomerization of 1-Aryl-1,3-Butadienes: Influence of Substituent on Photoreactivity—Structural and Photochemical Insights

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript by Dettori et al. describes the synthesis and evaluation of a series of substituted aryl 1,3 butadienes. The compounds were readily synthesized, and showed photoswitching behavior when irradiated with UV light. The manuscript is both very detailed and yet also is lacking some critical explanation and experiments (see below), but with revision it should be a useful addition to the literature.

This work should be of interest to photochemists interested in aryl butadiene photoswitches and to synthetic organic chemists interested in making this family of compounds.

Major comments:

My largest concern is about the photochemistry, it is necessary to report UV/visible absorption spectra for these compounds (both the E and the Z isomers)! This gives the reader critical information about how well the UV light used for the isomerizations (predominantly 254 nm, but also 365 nm) are absorbed by the compounds.

More experimental detail is needed for the photochemistry.

1.There is no mention of using quartz NMR tubes/cuvettes, but standard glass strongly absorbs 254 nm light, so an unknown percentage of photons from the lamps are getting through.

2.On the lamp illumination, (lines 218-221) how was intensity measured? With a power meter (what make/model)? Is the reported value from the combined lamps, or just one? How close were the lamps to the sample? What was the temperature of the sample over time?

CDCl3 is acidic, was it neutralized (e.g. with basic alumina) before use? Perhaps acid catalyzed decomposition. What about exclusion of oxygen (e.g. sparging N2 gas)?

I am concerned about the data presented in figure 4, there are not enough data points recorded for each curve, and no line fitting was done (just connecting the points with straight lines is not helpful). Some of the compounds, particularly E-1d, E-1f and both Z compounds look like there is significant deviation from the expected line fit in at least one of the reported points.

Also on figure 4 and the related text, There needs to be some explanation given for why 1g and 1c cross and then diverge when starting from E or Z and irradiating. 1g in particularly seems to have a ~20% E isomer content difference, which is surprising and seems unlikely.

More explanation of choice of derivative synthesized is needed, even if it is just because of what was on hand. More electron donating groups are warranted (e.g. amine or alkyl), as are more electron withdrawing groups (cyano, CF3). I noticed that R4 always H, why mention it at all then?

Author Response

Comment 1

Response 1

We thank the reviewer for highlighting this important point. In response to this request, we have now recorded and included the UV/Vis absorption spectra for all compounds in both their E and Z configurations. These spectra provide essential information regarding the absorption efficiency at the irradiation wavelengths employed in our experiments (254 nm and 365 nm). The corresponding spectra have been added to the Supporting Information (Figure S29-S30) and a discussion has been incorporated into the revised manuscript (lines 505-530).

Comment 2

There is no mention of using quartz NMR tubes/cuvettes, but standard glass strongly absorbs 254 nm light, so an unknown percentage of photons from the lamps are getting through.

Response 2

We thank the reviewer for this important observation. We indeed used standard glass class B glass NMR tubes thin wall 0.43mm for the photochemical experiments. Although standard glass absorbs strongly at 254 nm, the reaction does not rely exclusively on this wavelength in fact, the lamp employed in our setup emits a broader spectrum, including wavelengths above 300 nm, which are efficiently transmitted through glass and are sufficient to promote the observed photochemical transformation.

Comment 3

On the lamp illumination, (lines 218-221) how was intensity measured? With a power meter (what make/model)? Is the reported value from the combined lamps, or just one? How close were the lamps to the sample? What was the temperature of the sample over time?

Response 3

The illumination intensity corresponds to the value reported in the instrument specifications: 6-watt, 254-365 mm, 0-16 Ampers, 230V-50-60 Hz and it was not independently measured with a power meter. The photoisomerization experiments were carried out in a fume hood, and the sample temperature was monitored using a standard thermometer. Under these conditions, the temperature remained stable within the 20–22 °C range throughout the experiments. Regarding lamp positioning, the lamps were placed at the standard fixed distance provided by the instrument's setup; in our configuration, the distance between the lamps and the NMR tube was approximately 2 cm.

Comment 4

CDCl₃ is acidic, was it neutralized (e.g. with basic alumina) before use? Perhaps acid catalyzed decomposition. What about exclusion of oxygen (e.g. sparging N2 gas)?

Response 4

CDCl₃ was used as received, without prior neutralization. In this preliminary study, our aim was not to investigate the effect of solvent acidity but rather to identify the solvent providing the best overall performance for our photoisomerization experiments. For the same reason, no specific oxygen-exclusion procedures (such as N₂ sparging) were applied at this stage.

Comment 5

Response 5

In this work, our aim was not to perform a detailed kinetic analysis or evaluate deviations and standard errors in the fitting. Rather, we intended to assess, for each compound, the qualitative evolution of the photoisomerization process and determine the time required to reach the steady-state photostationary distribution. For this reason, the curves were presented as simple point-to-point connections to illustrate the temporal trend. We nevertheless appreciate the reviewer’s insightful remark regarding the behavior of compounds (E)-1d and (E)-1f and the (Z) corresponding isomers (Z)-1d and (Z)-1f. Indeed, these species appear to display a different trend compared to the others, and this deviation highlights interesting features that merit further investigation in future kinetic and mechanistic studies.

Comment 6

Response 6

We appreciate the reviewer's attention to this issue: it highlights mechanistic subtleties important for interpreting the relative reactivities of the series. Regarding the crossover and subsequent divergence of kinetics for 1g and 1c when irradiated from the E or Z side, and in particular the approximately 20% difference in E content for 1g, we agree that this behavior is noteworthy. Several explanations, not mutually exclusive, can account for observations such as the different spectral properties of the pure isomers: if the E and Z isomers have different absorption coefficients at the irradiation wavelength, the effective excitation rates from each isomer will be different, which can produce crossover kinetics and different photostationary compositions.

Comment 7

Response 7

In this preliminary study, our aim was to obtain an initial assessment of the photoisomerization behaviour within a small set of substituted dienes, chosen mainly based on synthetic availability and to provide a first comparison between electron-rich and electron-poor systems. We fully agree that a broader and more systematically designed set of derivatives, including stronger electron-donating groups (e.g., amine or alkyl substituents) as well as more strongly electron-withdrawing groups (such as cyano) would allow a deeper understanding of the substituent effects on the photochemical response. In future work, we plan to extend the investigation to a larger series of dienes substituted not only at positions 2 and 3, but also at position 4 and 5, incorporating both electron-donating and electron-withdrawing functionalities to obtain a more complete structure–reactivity picture. Regarding substituent R4, we thank the reviewer for pointing out that this position is always occupied by hydrogen in our series. We will revise the figure and the corresponding text to avoid unnecessary mention of R4 and to improve clarity.

Reviewer 2 Report

Comments and Suggestions for Authors

Dettori et al. present a well-structured study on the photoinduced geometric isomerization of 1-aryl-1,3-butadienes, combining synthetic chemistry, photochemical experiments, NMR spectroscopy, and DFT calculations. The work provides valuable insights into the structural and photochemical behavior of these conjugated systems, with clear experimental evidence and computational support. However, several issues should be addressed before publication:

The current title, “Photoinduced Geometric Isomerization of 1-Aryl-1,3-Butadienes: Structural and Photochemical Insights,” is appropriate but could be made more precise. Since the study systematically examines the effect of aryl substituents (electron-donating vs. electron-withdrawing) on isomerization efficiency, the title might be refined to highlight this aspect.
In the discussion of solvent effects on photoisomerization efficiency (Section 3.2), the authors cite Seaho et al. for stability in CDCl₃ CD₃OD but overlook relevant literature on solvent polarity and proton-donating ability in influencing photoisomerization pathways. Key references related with this aspect should be included to contextualize the solvent-dependent behavior.
The computational section (3.4) states that “a relaxed scan was performed in Gaussian 16” but does not specify whether these were constrained optimizations or full geometry optimizations at each point. Clarifying the computational protocol (e.g., “constrained optimizations with fixed dihedral angles”) would improve reproducibility.
A thorough proofreading is recommended to improve readability and consistency.

This manuscript presents a solid contribution to the field of photoresponsive conjugated systems. With the above revisions, it will be suitable for publication. I recommend minor revisions to address the points outlined above.

Author Response

Comment 1

The current title, “Photoinduced Geometric Isomerization of 1-Aryl-1,3-Butadienes: Structural and Photochemical Insights,” is appropriate but could be made more precise. Since the study systematically examines the effect of aryl substituents (electron-donating vs. electron-withdrawing) on isomerization efficiency, the title might be refined to highlight this aspect.

Response 1

We thank the reviewer for this helpful suggestion. In accordance with the comment, we have revised the title to better highlight the systematic examination of aryl substituent effects on photoisomerization efficiency. The new title is: Photoinduced Geometric Isomerization of 1-Aryl-1,3-Butadienes: Influence of Substituent on Photoreactivity. Structural and Photochemical Insights.

Comment 2

In the discussion of solvent effects on photoisomerization efficiency (Section 3.2), the authors cite Seaho et al. for stability in CDCl₃ CD₃OD but overlook relevant literature on solvent polarity and proton-donating ability in influencing photoisomerization pathways. Key references related with this aspect should be included to contextualize the solvent-dependent behavior.

Response 2

In accordance with the comment, we have added a brief discussion (Lines 308-310) and a relevant reference (37) discussing the role of solvent polarity and proton-donating ability in influencing photoisomerization pathways. These reference contextualize the solvent-dependent behavior observed in a similar system in the discussion of solvent effects on photoisomerization efficiency.

Comment 3

The computational section (3.4) states that “a relaxed scan was performed in Gaussian 16” but does not specify whether these were constrained optimizations or full geometry optimizations at each point. Clarifying the computational protocol (e.g., “constrained optimizations with fixed dihedral angles”) would improve reproducibility.

Response 3

The extensive exploration of the molecular potential energy surface (PES) was conducted using a relaxed scan optimization approach, in which specific dihedral angles were constrained to systematically sample the conformational space. A step size of 15° was used for the primary dihedral, while a larger step size of 90° was employed for the secondary dihedral to reduce computational cost without compromising the overall coverage. This protocol generated a total of 96 optimized structures per sample, which provided a comprehensive and satisfactory approximation of the accessible conformational space. The resulting structures were subsequently analyzed to identify low-energy conformers and to evaluate their potential influence on the photochemical properties and isomerization behaviour

Comment 4

A thorough proofreading is recommended to improve readability and consistency.

Response 4

We sincerely thank the reviewer for this constructive suggestion. We have carefully proofread the manuscript to improve readability, ensure consistency, and enhance the overall clarity of the text

Reviewer 3 Report

Comments and Suggestions for Authors

The article reports the well-organized investigation of isomeric conversion for the set of 1-aryl-1,3-butadienes, some of which are important bioactive substances. The set contains the aryl derivatives with different substituents in the aryl ring that allows authors to make conclusions about the influence of electron effects on the isomerization processes. The materials presented are new and well founded. References are mostly corresponding to the topic of investigation. The article is well organized and written in good scientific language. I suppose that it could be published with minor corrections:

Line 167. «To a solution of compounds3a-g(1 eq), in dioxane (10 mL)». Before this phrase no information can be found about 1a-g, 3a-g. Thus, the scheme 1 should be placed before or should be mentioned in the phrase for the reader can understand.
Line 276. Scheme 1. Correct the formula of CuSO4 on the Scheme.
The authors mentioned that microwave heating allows more rapid reaction of dehydration. But the crucial is the E/Z excess. Can it also be enhanced with MW?
It is not surprising that CHCl3 is not good for the photoreactions. Chlorinated solvents can undergo UV transformation itself or with different reagents. Especially with wavelength < 300 nm. Probably authors can discuss it.

https://www.tandfonline.com/doi/full/10.1080/00958970903582696

https://pubs.acs.org/doi/full/10.1021/ic800684v

https://www.sciencedirect.com/science/article/pii/S1010603017318634

https://link.springer.com/article/10.1007/s10967-022-08690-7

Author Response

Comment 1

Line 167. «To a solution of compounds 3a-g (1 eq), in dioxane (10 mL)». Before this phrase no information can be found about 1a-g, 3a-g. Thus, the scheme 1 should be placed before or should be mentioned in the phrase for the reader can understand.

Response 1

To improve clarity and facilitate understanding, we have inserted a reference to Scheme 1 at line 169, allowing readers to readily identify compounds 1a-g and 3a-g at this point in the text.

Comment 2

Line 276. Scheme 1. Correct the formula of CuSO₄ on the Scheme.

Response 2

Done

Comment 3

The authors mentioned that microwave heating allows more rapid reaction of dehydration. But the crucial is the E/Z excess. Can it also be enhanced with MW?

Response 3

The dehydration reaction was also performed under conventional heating, which required significantly longer reaction times. However, no substantial differences in terms of E/Z ratios were observed compared to microwave-assisted conditions. Thus, while microwave heating accelerates the reaction, it does not appear to significantly influence the E/Z selectivity

Comment 4

It is not surprising that CHCl3 is not good for the photoreactions. Chlorinated solvents can undergo UV transformation itself or with different reagents. Especially with wavelength < 300 nm. Probably authors can discuss it.

https://www.tandfonline.com/doi/full/10.1080/00958970903582696

https://pubs.acs.org/doi/full/10.1021/ic800684v

https://www.sciencedirect.com/science/article/pii/S1010603017318634

https://link.springer.com/article/10.1007/s10967-022-08690-7

Response 4

We thank the reviewer for this important observation. Indeed, chlorinated solvents such as CHCl₃ can undergo photochemical transformations under UV irradiation, particularly at wavelengths below 300 nm, which may interfere with the intended photoisomerization. In our experiments, we chose CDCl₃ primarily as a standard solvent to maintain consistency across the series of compounds. We have briefly discussed this point in the revised manuscript, acknowledging the potential limitations associated with chlorinated solvent (lines 320-321).