University of Groningen
Donor-Acceptor Stenhouse Adducts
Lerch, Michael Markus
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2018
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Lerch, M. M. (2018). Donor-Acceptor Stenhouse Adducts. Rijksuniversiteit Groningen.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
195
Published as:
Chem. Soc. Rev., 2018, 47, 1910-1937
DOI: 10.1039/c7cs00772h
Michael M. Lerch, Wiktor Szymański* and Ben L. Feringa*
Chapter 7
Conclusion
196 Chapter 7
In conclusion, Stenhouse photoswitches are an interesting and nascent class of photoswitches. Despite their origins dating back over 150 years, many aspects are still poorly understood and shortcomings need improvement. With their successful work in recent years, the groups of Read de Alaniz and Hawker, together with other groups, have set a solid foundation to establish donor–acceptor Stenhouse adducts and to challenge and complement existing prevalent photoswitches such as azobenzenes, diarylethenes, spiropyrans, hemithioindigo photoswitches and stilbenes. Within these efforst, this thesis has provided in-depth studies
on DASA’s photoswitching mechanism (Chapters 3–6)1–3 and introduced orthogonal
photoswitching (Chapter 2).4
Particularly strong advantages of DASAs are that they are inherent visible light switchable negative photochromes that are rapidly synthesized in a modular fashion. They further show a large change of polarity, dipole moment, geometry and UV/vis spectrum upon photoswitching. The structural scope, so far explored, allows to choose different structures for different types of applications and their modular architecture enables chemists to easily tune their properties – once they are understood. However, the overall structural diversity is rather limited, allowing for only two tolerated acceptor moieties. Currently, rational tuning of the thermal stability of the cyclized form is not possible. Moreover, the irreversible cyclization of DASAs in the dark in polar protic solvents can pose a problem for biological applications. While in some cases their delicate photoswitching behavior in different environments can be beneficial for applications, in other cases these properties might currently limit DASAs’ use. Mechanistically, DASA’s photoswitching is likely governed by a photoisomerization around C2–C3 adjacent to the hydroxyl group and a subsequent rotation around C3–C4. Optimally spatially arranged, the molecule then undergoes a thermal, conrotatory 4π–electrocyclization to form a cyclopentenone. Structural features have a tremendous influence on the photoswitching as highlighted for instance by the difference between first and second-generation DASAs, thus enabling the synthetic chemist to specifically tailor photoswitches for a given system. From existing applications, the potential and short-comings of DASAs can be studied, insights gained and lessons learned. Thus, for this photoswitch class to realize its full potential, we identify the following factors that will be essential for overcoming current limitations:
Structure-property relationships: Understanding the mechanism of
photoswitching and what structural features of Stenhouse photoswitches are responsible for which properties (ε, φ, t1/2, λmax, solubility, photoswitching kinetics) is essential for deliberate use and tuning of photoswitches for applications.
(Excited) energy surface (computation): A solid computational understanding of
Stenhouse switch behavior through its energy surface will allow to identify areas for improvements and help synthetic chemists to devise novel target structures.
Solvent effects: A current major limitation of Stenhouse photoswitching is its
197 Conclusion
7
understanding of the governing parameters for switching in various mediais essential. However, it should be mentioned that strong solvent-dependent photoswitching can also be beneficial, if this behavior is deliberately taken into account when devising applications.
Bistability: Some applications require the use of bistable photoswitches. So far,
DASAs as T-type photoswitches rely on one wavelength for photoswitching and a thermal back-isomerization. Having bi-directional control with different wavelengths of irradiation would substantially extend the scope of Stenhouse switch applications, but will require innovative and unconventional solutions.
Extending the acceptor scope: Currently, DASAs are limited to two acceptors
either based on Meldrum’s acid or 1,3-disubstituted barbituric acid. Besides potential problems of novel acceptors (e.g. 1,3-indandione in the case of compound
13, Chapter 1) with photoswitching, the synthesis of DASA target structures is
often the limiting factor. The development of novel synthetic routes to access such structures beyond the current use of Zincke-type reactivity is strongly encouraged.
Photopharmacology:5–7 Achieving full control over photoswitching under
physiological conditions remains a main goal. Herein, hydrolytic stability and high solubility in aqueous environments will be a key factor. The potential for orthogonal photocontrol in combination with other photoswitchable bioactive compounds constitutes a powerful future tool for biomedical research.
Near-Infrared (NIR) photoswitching: Currently the absorption spectra of the
most red-shifted DASA photoswitches tail above 700 nm in dichloromethane, thus allowing for convenient visible light and NIR operation in organic solvents and material science. However, DASAs currently do not show high enough solubility in aqueous environments and if soluble show a large blue-shift of absorption. The so-called “near-infrared phototherapeutic window”7–11 would be ideal for medical
applications, but would require further red-shifting of compounds.
For the coming years, we envision key advances both in understanding and improvement of Stenhouse photoswitches that will be essential for rapid and productive development of the field. Researchers from different backgrounds will have to work together to better understand the dynamic behavior of Stenhouse switches and to realize their full potential. Notably, reversible switching on surfaces and in polar protic media (e.g. under physiological conditions) and expanding the synthetic scope of these switches are most pressing issues. Given the rapid development this class of photoswitches has undergone in the last three years, we are confident of many interesting and exciting opportunities and applications to come. After being dormant for over a century, the future of Stenhouse photoswitches is particularly bright.
198 Chapter 7
References
1. Lerch, M. M.; Wezenberg, S. J.; Szymański, W.; Feringa, B. L. J. Am. Chem. Soc. 2016, 138 (20), 6344–6347.
2. Di Donato, M.; Lerch, M. M.; Lapini, A.; Laurent, A. D.; Iagatti, A.; Bussotti, L.; Ihrig, S. P.; Medved’, M.; Jacquemin, D.; Szymański, W.; Buma, W. J.; Foggi, P.; Feringa, B. L. J. Am. Chem. Soc. 2017, 139 (44), 15596–15599.
3. Lerch, M. M.; Medved’, M.; Lapini, A.; Laurent, A. D.; Iagatti, A.; Bussotti, L.; Szymański, W.; Buma, W. J.; Foggi, P.; Di Donato, M.; Feringa, B. L. J.
Phys. Chem. A 2018, 122 (4), 955–964.
4. Lerch, M. M.; Hansen, M. J.; Velema, W. A.; Szymański, W.; Feringa, B. L. Nat. Commun. 2016,
7, 12054.
5. Velema, W. A.; Szymański, W.; Feringa, B. L. J. Am.
Chem. Soc. 2014, 136 (6), 2178–2191.
6. Broichhagen, J.; Frank, J. A.; Trauner, D. Acc.
Chem. Res. 2015, 48 (7), 1947–1960.
7. Lerch, M. M.; Hansen, M. J.; van Dam, G. M.; Szymanski, W.; Feringa, B. L. Angew. Chem. Int.
Ed. 2016, 55 (37), 10978–10999.
8. Bléger, D.; Hecht, S. Angew. Chem. Int. Ed. 2015, 54 (39), 11338–11349.
9. Dong, M.; Babalhavaeji, A.; Samanta, S.; Beharry, A. A.; Woolley, G. A. Acc. Chem. Res. 2015, 48 (10), 2662–2670.
10. Weissleder, R.; Ntziachristos, V. Nat. Med. 2003, 9 (1), 123–128.
11. Stolik, S.; Delgado, J. A.; Pérez, A.; Anasagasti, L.
J. Photochem. Photobiol. B Biol. 2000, 57 (2–3),
199 Conclusion