Coumarinyl(thienyl)thiazoles as new fluorescent molecular photoswitches

A number of new photochromic 3-(4-phenylthiazol-5-yl)-and 3-(4-hetarylthiazol-5-yl)- coumarins has been synthesized. These compounds possess properties of molecular photo- switches providing a reversible change of the fluorescence intensity in the visible region of the spectrum upon alternating irradiation of their solutions with the visible and UV light. Irradiation with the UV light (λ < 400 nm) leads to their electrocyclization and loss of fluorescence, whereas irradiation of the cyclic form with the visible light (λ < 400 nm) returns the system to the state with the original absorption and fluorescence spectra. Switching of fluorescence is also observed in polymer matrices.     

Photomechanical polymer hydrogels based on molecular photoswitches

As intelligent materials responsive to light, photomechanical hydrogels not only possess high-water content, excellent softness and biocompatibility, but also can accomplish various mechanical motions upon spatiotemporal stimulation of external light, which exhibit great potential in biomedical and underwater bionic fields. Molecular photoswitches have been used broadly in preparation of photomechanical hydrogels owing to their high photosensitivity and reversible molecular structure transformations induced by light. Herein, the current progress of photomechanical hydrogels based on typical molecular photoswitches such as spiropyran, azobenzene, and hexaarylbiimidazole (HABI) are introduced. Especially, as a promising building unit for photomechanical hydrogels, HABI has been highlighted due to the unique molecular structures and reversible photoswitching capability. HABI-derived polymer hydrogels demonstrate flexible mechanical behaviors upon localized light irradiation. The characteristics and challenges of photomechanical hydrogels based on molecular photoswitches are also prospected.     

Multimodal fluorescence modulation using molecular photoswitches and upconverting nanoparticles

The intensity and colour of the light emitted from upconverting nanoparticles is controlled by the state of photoresponsive dithienylethene ligands decorated onto the surface of the nanoparticles. By selectively activating one or both ligands in a mixed, 3-component system, a multimodal read-out of the emitted light is achieved.     

Data-driven discovery of molecular photoswitches with multioutput Gaussian processes

Photoswitchable molecules display two or more isomeric forms that may be accessed using light. Separating the electronic absorption bands of these isomers is key to selectively addressing a specific isomer and achieving high photostationary states whilst overall red-shifting the absorption bands serves to limit material damage due to UV-exposure and increases penetration depth in photopharmacological applications. Engineering these properties into a system through synthetic design however, remains a challenge. Here, we present a data-driven discovery pipeline for molecular photoswitches underpinned by dataset curation and multitask learning with Gaussian processes. In the prediction of electronic transition wavelengths, we demonstrate that a multioutput Gaussian process (MOGP) trained using labels from four photoswitch transition wavelengths yields the strongest predictive performance relative to single-task models as well as operationally outperforming time-dependent density functional theory (TD-DFT) in terms of the wall-clock time for prediction. We validate our proposed approach experimentally by screening a library of commercially available photoswitchable molecules. Through this screen, we identified several motifs that displayed separated electronic absorption bands of their isomers, exhibited red-shifted absorptions, and are suited for information transfer and photopharmacological applications. Our curated dataset, code, as well as all models are made available at https://github.com/Ryan-Rhys/The-Photoswitch-Dataset.

We present a data-driven discovery pipeline for molecular photoswitches through multitask learning with Gaussian processes. Through subsequent screening, we identify several motifs with separated and red-shifted electronic absorption bands.     

Designing chimeric LOV photoswitches

The LOV domain from Avena sativa has a C-terminal (Jα) helix that dissociates and unfolds when the protein is exposed to blue light. Using computational protein design methods, Lungu et?al., in this issue of Chemistry & Biology, created chimeric Jα sequences that show photo-controlled interactions with chosen targets.     

Azobenzene photoswitches for biomolecules

The photoisomerization of azobenzene has been known for almost 75 years but only recently has this process been widely applied to biological systems. The central challenge of how to productively couple the isomerization process to a large functional change in a biomolecule has been met in a number of instances and it appears that effective photocontrol of a large variety of biomolecules may be possible. This critical review summarizes key properties of azobenzene that enable its use as a photoswitch in biological systems and describes strategies for using azobenzene photoswitches to drive functional changes in peptides, proteins, nucleic acids, lipids, and carbohydrates (192 references).     

Photocontrol of peptide secondary structure through non-azobenzene photoswitches

The rapidly expanding field of photoswitchable biomolecules is a major frontier in scientific research and provides unparalleled opportunities for studying biological pathways and disease progression. In particular, the development of photochromic peptides has delivered both scientific tools and candidates for photopharmaceuticals. The action and function of the peptide can be remotely altered using light, allowing detection of its biological role in complex biological settings, while also enabling folding studies that provide greater understanding of protein structure dynamics. In this review we provide a key, comprehensive overview of the different types of photoswitches that have been used to control peptide structure, excluding the already extensively reviewed azobenzene. This will help address the question as to which synthetic photoswitch to use in a given study.     

Acid-catalysed liquid-to-solid transitioning of arylazoisoxazole photoswitches

Molecular photoswitches play a vital role in the development of responsive materials. These molecular building blocks are particularly attractive when multiple stimuli can be combined to bring about physical changes, sometimes leading to unexpected properties and functions. The arylazoisoxazole molecular switch was recently shown to be capable of efficient photoreversible solid-to-liquid phase transitions with application in photoswitchable surface adhesion. Here, we show that the arylazoisoxazole forms thermally stable and photoisomerisable protonated Z- and E-isomers in an apolar aprotic solvent when the pK_a of the applied acid is sufficiently low. The tuning of isomerisation kinetics from days to seconds by the pK_a of the acid not only opens up new reactivity in solution, but also the solid-state photoswitching of azoisoxazoles can be efficiently reversed with selected acid vapours, enabling acid-gated photoswitchable surface adhesion.

Molecular photoswitches are versatile components for materials with bistable and photoreversible properties. Here, we enrich the functionality of the arylazoisoxazole molecular switch by analyzing its photoresponsive protonated Z- and E-isomers.     

New synthetic route to substituted dihydroazulene photoswitches

A new procedure for functionalization of the dihydroazulene photoswitch on its seven-membered ring was developed, which has allowed isolation of the first dihydroazulene with a phenyl substituent at position 5 from a mixture of regioisomers. Light-induced ring-opening to the corresponding vinylheptafulvene and the thermal back-reaction was studied in detail.     

Linked photoswitches where both photochromes open and close

In the dithienylethene photochrome series, linking two photochromes together directly, or with an ethynyl spacer, shuts down the photoswitching of one of the photochromes. We report here, that for dihydropyrenes, two photochromes can be linked together without affecting the ability of either to photoswitch. [reaction--see text]     

Metallofullerene photoswitches driven by photoinduced fullerene-to-metal electron transfer

We report on the discovery and detailed exploration of the unconventional photo-switching mechanism in metallofullerenes, in which the energy of the photon absorbed by the carbon cage π-system is transformed to mechanical motion of the endohedral cluster accompanied by accumulation of spin density on the metal atoms. Comprehensive photophysical and electron paramagnetic resonance (EPR) studies augmented by theoretical modelling are performed to address the phenomenon of the light-induced photo-switching and triplet state spin dynamics in a series of Y_xSc_3−xN@C₈₀ (x = 0–3) nitride clusterfullerenes. Variable temperature and time-resolved photoluminescence studies revealed a strong dependence of their photophysical properties on the number of Sc atoms in the cluster. All molecules in the series exhibit temperature-dependent luminescence assigned to the near-infrared thermally-activated delayed fluorescence (TADF) and phosphorescence. The emission wavelengths and Stokes shift increase systematically with the number of Sc atoms in the endohedral cluster, whereas the triplet state lifetime and S₁–T₁ gap decrease in this row. For Sc₃N@C₈₀, we also applied photoelectron spectroscopy to obtain the triplet state energy as well as the electron affinity. Spin distribution and dynamics in the triplet states are then studied by light-induced pulsed EPR and ENDOR spectroscopies. The spin–lattice relaxation times and triplet state lifetimes are determined from the temporal evolution of the electron spin echo after the laser pulse. Well resolved ENDOR spectra of triplets with a rich structure caused by the hyperfine and quadrupolar interactions with ¹⁴N, ⁴⁵Sc, and ⁸⁹Y nuclear spins are obtained. The systematic increase of the metal contribution to the triplet spin density from Y₃N to Sc₃N found in the ENDOR study points to a substantial fullerene-to-metal charge transfer in the excited state. These experimental results are rationalized with the help of ground-state and time-dependent DFT calculations, which revealed a substantial variation of the endohedral cluster position in the photoexcited states driven by the predisposition of Sc atoms to maximize their spin population.

Photoexcitation mechanism of Y_xSc_3−xN@C₈₀ metallofullerenes is studied by variable-temperature photoluminescence, advanced EPR techniques, and DFT calculations, revealing photoinduced rotation of the endohedral cluster.     

Trace mild acid-catalysed Z → E isomerization of norbornene-fused stilbene derivatives: intelligent chiral molecular photoswitches with controllable self-recovery

Stilbene derivatives have long been known to undergo “acid-catalyzed” Z → E isomerization, where a strong mineral acid at high concentration is practically necessary. Such severe reaction conditions often cause undesired by-reactions and limit their potential application. Herein, we present a trace mild acid-catalyzed Z → E isomerization found with stilbene derivatives fused with a norbornene moiety. By-reactions, such as the migration of the C C double bond and electrophilic addition reactions, were completely inhibited because of the ring strain caused by the fused norbornene component. Direct photolysis of the E isomers at selected wavelengths led to the E → Z photoisomerization of these stilbene derivatives and thus constituted a unique class of molecular switches orthogonally controllable by light and acid. The catalytic amount of acid could be readily removed, and the Z → E isomerization could be controlled by turning on/off the irradiation of a photoacid, which allowed repeated isomerization in a non-invasive manner. Moreover, the Z isomer produced by photoisomerization could spontaneously self-recover to the E isomer in the presence of a catalytic amount of acid. The kinetics of Z → E isomerization were adjustable by manipulating catalytic factors and, therefore, unprecedented molecular photoswitches with adjustable self-recovery were realized.

Quantitative Z → E isomerization was catalyzed by trace mild acids to offer molecular switches orthogonally controllable by acid and light.     

Comparison of two thioxopeptide bond photoswitches in insect kinin

<正>The photoisomerization abilities of secondary thioxopeptide bond(CS-NH) and thioxo prolyl bond(CS-N) incorporated into the C-terminal pentapeptide of insect kinin were compared.H-Phe-Phe-Ψ[CS-NH]-D-Ala-Trp-Gly-NH_2 and H-Phe-Tyr-Ψ[CS-N]- Pro-Trp-Gly-NH_2 were studied by UV-vis absorption.The isomerization energy barriers of the two segments,Ac-Phe-Ψ[CS-NH]- D-Ala-NH_2 and Ac-Tyr-Ψ[CS-N]-Pro-NH_2 picked from the two peptides,were calculated using ab initio method.The cis isomer of CS-N is more stable than that of CS-NH due to higher energy barrier,so the former is more suitable in peptide structure-activity relationship studies.     

Tailoring the optical and dynamic properties of iminothioindoxyl photoswitches through acidochromism

Multi-responsive functional molecules are key for obtaining user-defined control of the properties and functions of chemical and biological systems. In this respect, pH-responsive photochromes, whose switching can be directed with light and acid–base equilibria, have emerged as highly attractive molecular units. The challenge in their design comes from the need to accommodate application-defined boundary conditions for both light- and protonation-responsivity. Here we combine time-resolved spectroscopic studies, on time scales ranging from femtoseconds to seconds, with density functional theory (DFT) calculations to elucidate and apply the acidochromism of a recently designed iminothioindoxyl (ITI) photoswitch. We show that protonation of the thermally stable Z isomer leads to a strong batochromically-shifted absorption band, allowing for fast isomerization to the metastable E isomer with light in the 500–600 nm region. Theoretical studies of the reaction mechanism reveal the crucial role of the acid–base equilibrium which controls the populations of the protonated and neutral forms of the E isomer. Since the former is thermally stable, while the latter re-isomerizes on a millisecond time scale, we are able to modulate the half-life of ITIs over three orders of magnitude by shifting this equilibrium. Finally, stable bidirectional switching of protonated ITI with green and red light is demonstrated with a half-life in the range of tens of seconds. Altogether, we designed a new type of multi-responsive molecular switch in which protonation red-shifts the activation wavelength by over 100 nm and enables efficient tuning of the half-life in the millisecond–second range.

Protonation of an ITI molecular photoswitch shifts its absorption to the orange/red part of the spectrum and allows for manipulation of the thermal half-life of the photogenerated E-isomer over three orders of magnitude.     

Oligospiroketals as novel molecular rods

A modular approach for the synthesis of molecular rods based on oligospiroketals has been developed. The strategy relies on different terminal and intermediate segments, which are joined by ketal formation between ketones and diols. For this purpose it was necessary to develop a new ketalization method to circumvent some problems related with the established methods. The terminal segments are either derived from 4-piperidinone or from 4-oxocyclohexane carboxylic acid whereas the intermediate segments rest on pentaerythritol and cyclohexane-1,4-dione. A series of trispiro (14-18), hexaspiro (19) and nonaspiro (20) compounds have been prepared and characterized. From these we realized that it is imperative to use solubility enhancing groups if more than seven rings are joined.     

Redesigning donor–acceptor Stenhouse adduct photoswitches through a joint experimental and computational study

Many studies have recently explored a new class of reversible photoswitching compounds named Donor–Acceptor Stenhouse Adducts (DASAs). Upon light irradiation, these systems evolve from a coloured open-chain to a colourless closed-ring form, while the thermal back-reaction occurs at room temperature. In order to fulfill the requirements for different applications, new molecules with specific properties need to be designed. For instance, shifting the activation wavelength towards the red part of the visible spectrum is of relevance to biological applications. By using accurate computational calculations, we have designed new DASAs and predicted some of their photophysical properties. Starting from well-studied donor and acceptor parts, we have shown that small chemical modifications can lead to substantial changes in both photophysical and photoswitching properties of the resulting DASAs. Furthermore, we have also analysed how these substitutions impact the electronic structure of the systems. Finally, some pertinent candidates have been successfully synthesized and their photoswitching properties have been characterized experimentally.

New photoswitch Donor–Acceptor Stenhouse Adducts (DASAs) have been synthesized thanks to accurate computational chemistry predictions. They possess good properties, notably red light activation.     

Indicator displacement assays as molecular timers

Dynamic mixtures of Rh-dye complexes can be used to determine the history of chemical events such as the addition of ATP and ADP by UV-vis spectroscopy.     

Flexible polyfluorinated bis-diazirines as molecular adhesives

Motivated by a desire to develop flexible covalent adhesives that afford some of the same malleability in the adhesive layer as traditional polymer-based adhesives, we designed and synthesized two flexible, highly fluorinated bis-diazirines. Both molecules are shown to function as effective crosslinkers for polymer materials, and to act as strong adhesives when painted between two polymer objects of low surface energy, prior to thermal activation. Data obtained from lap-shear experiments suggests that greater molecular flexibility is correlated with improved mechanical compliance in the adhesive layer.

Flexible, highly fluorinated covalent adhesives are synthesized, and are shown to afford comparable C–H insertion efficiency and adhesion strength relative to a rigid analogue, while providing improved mechanical compliance in the adhesion layer.     

Organized molecular systems as reaction media

Media are among the most important factors to be considered for organic synthesis in soft and non-polluting conditions satisfying the conditions for sustainable development. Organized Molecular Systems (OMS) are very useful when efforts are being made to apply the twelve green chemistry principles, more precisely to replace organic solvents, to carry out reactions in water, to employ catalysis and biocatalysis, to economize molecules (and, of course, of atoms) and to work with low-energy conditions. These OMS posses a number of advantages: solubilization of substances that are not normally soluble in the continuous phase of OMS, localization of reactants and products, and selective orientation and stabilization of the various entities in the various stages of the reaction. Rapid and selective reactions of preparative amounts of substrate can be carried out in such media, which are also very suitable for mechanistic studies. First, we performed organic photoreactions in microemulsions (macroscopically homogeneous and transparent media). Thus, we were able to confirm the interfacial localization of the processes by means of chemical internal sensors and infrared spectroscopy; to propose a formulation strategy for diminishing the number of substrates in the medium (molecular economy principle); and to use high interfacial concentration to carry out reactions in the liquid phase although they are generally only possible in the solid state. The most important scientific point was the demonstration of the generalization of the amphiphilicity concept, by using polar non-aqueous solvents. 1986 saw the end of a controversy concerning the use of formamide in place of water. With this type of solvent, we have been able to perform important reactions: the Wacker process, Diels-Alder reactions, and olefin amidations. Then we postulated the formation of aggregates without surfactants if differential solvations were operative. All organic reactions can be influenced by the spontaneous formation of aggregates. To finish, with such systems, it is possible to orientate the reactivity of competitive reactions (e.g. cyclization and polymerization) and help to protect the environment, for example in the synthesis of clean surfactants in clean conditions. With the extension of these observations and results to the use of rigid objects (similar to rigid micelles) we were able to obtain very high enantioselective excess in chiral processes.