Photoswitchable Units Research Articles

Meta-connected Oligo-Azobenzenes Outperform Their Para Counterparts.

Systems with multiple photoswitchable units in one molecule have attracted considerable attention in the past years as they are useful for a broad variety of possible applications. Especially, linked azobenzenes sharing one benzene ring are of high interest since their direct linkage introduces an additional photoswitchable unit at only small increase in molecular weight. In this spirit, linear oligoazobenzenes had been synthesized, though their photochemical properties have only been investigated for short chain lengths. In this study, we use (time-dependent) density functional methodology for the evaluation of the excitations of meta- and para-connected oligo-azobenzenes to predict their switching ability. It becomes apparent, that the meta connection pattern enables each azobenzene subunit to act as an individual switchable unit, whereas they are strongly coupled and loose their individuality in para connection. Therefore, meta-oligo-azobenzenes are ideal candidates for future studies of azobenzene-based functional polymers, while para-oligo-azobenzenes are not.

Advancing Optoglycomics: Two Orthogonal Azobenzene Glycoside Antennas in One Glycocluster-Synthesis, Switching Cycles, Kinetics and Molecular Dynamics.

Carbohydrate recognition is essential for numerous biological processes and is governed by various factors within the supramolecular environment of the cell. Photoswitchable glycoconjugates have proven as valuable tools for the investigation and modulation of carbohydrate recognition as they allow to control the relative orientation of sugar ligands by light. In order to advance the possibilities of such an "optoglycomics" approach for the glycosciences, we have synthesized a biantennary glycocluster in which two glycoazobenzene antennas are conjugated to the 3- and 6-position of a scaffold glycoside. Orthogonal isomerization of the photoswitchable units was made possible by the different conjugation of the azobenzene moieties via an oxygen and a sulfur atom, respectively, and the ortho-fluorination of one of the azobenzene units. This design enabled a switching cycle comprising the EE, EZ and the ZZ isomer. This is the first example of an orthogonally photoswitchable glycocluster. The full analysis of its photochromic properties included the investigation of the isolated glycoazobenzene antennas allowing the comparison of the intra- versus the intermolecular orthogonal photoswitching. The kinetics of the thermal relaxation were analyzed in detail. A molecular dynamics study shows that indeed, the relative orientation of the glycoantennas and the distances between the terminal sugar ligands significantly vary depending on the isomeric state, as intended.

Photoresponsive Supramolecular Cages and Macrocycles.

The utilisation of light to achieve precise manipulation and control over the structure and function of supramolecular assemblies has emerged as a highly promising approach in the development of complex, configurable, or multifunctional systems and nanoscopic machine-like entities. In this minireview, we highlight recent examples of self-assembled and covalently bound cages and macrocycles with a focus on the external and internal functionalisation of a structure with a photoswitchable unit or the embedment of a photoswitch into the framework of a structure. Functionalising the interior or exterior of a supramolecular cage or macrocycle with a photoresponsive group enables control over different properties, such as guest binding or assembly in the solid-state, while the overall shape of the assembly often undergoes no significant change. By directly integrating a photoswitchable unit into the framework of a supramolecular structure, the isomerisation can either induce a geometry change, the disassembly, or the disassembly and reassembly of the structure. Historical and recent examples covered in this review are based on azobenzene, diarylethene, stilbene photoswitches, or alkene motors that were incorporated into macrocycles and cages constructed by metal-organic, dynamic covalent, or covalent bonds.

A bisphotochromic system featuring two modes of photoisomerization controlled by solvent polarity

Combining two or more photoswitchable units in one molecule results in multiphotochromic hybrids with attractive sophisticated performance. On-demand switching of light-induced isomerization pathways for such systems by change of solvent polarity is a virtually unexplored phenomenon. Using NMR spectroscopy, we have demonstrated that the competition between 6π-electrocyclization and E-/Z-isomerization of 2,3-bis(2,5-dimethylthiophen-3-yl)-5-(4-dialkylaminobenzylidene)cyclopent-2-en-1-ones depends on the solvent's nature. Cyclization of diarylethene predominates in less polar solvents, whereas isomerization of the arylidene moiety prevails in polar media. This result could be the starting point for the development of multiphotochromic hybrids with efficient solvent-controllable selectivity of photoreactions.

Nanostructured photoswitchable colloidal particles made of coordination polymer containing dimethyldihydropyrene units

Photochromic stimuli-responsive coordination polymers that offer on-demand molecular structure modifications are promising building blocks for next generation of multi-functional materials. Getting closer to some applications requires these materials to be in condensed phases, which is yet lacking. In this work, ≈ 300 - 450 nm colloidal particles made of a coordination polymer that includes dimethyldihydropyrene (DHP) as photoswitchable units have been synthesized. ZnDHP particles exhibit a photochromic behavior based on the reversible conversion of “closed” DHP units into “open” cyclophanediene (CDP). Ring opening in the condensed phase was triggered by visible light illumination while back-conversion was performed by either heating or irradiation with UV light. Experiments were monitored by UV–vis spectroscopy. Results showed good reversibility of the system with < 5 min back-conversion under UV irradiation. Nanostructure of the particles was studied by TEM and SAXS. Particles are made of 10 – 25 nm dense parallelepipedic nanoparticles organized into a slightly loose network. SAXS analysis demonstrates that ZnDHP particle structure is resilient to ZnCDP conversion. Finally, ability of ZnCDP-O2 particles to release singlet oxygen during their back-conversion to ZnDHP particles is demonstrated by EPR experiments.

Photoresponsive Small Molecule Enzyme Mimics.

Enzyme mimics emulate the catalytic activities of their natural counterparts. Light-responsive enzyme mimics are an emerging branch of biomimetic chemistry where the catalytic activities can be controlled reversibly by light. These light-responsive systems are constructed by incorporating a suitable photoswitchable unit around the active-site mimic. As these systems are addressable by light, they do not leave back any undesired side products, and their activation–deactivation can be easily controlled. Naturally, these systems have enormous potential in the field of on-demand catalysis. The synthetic light-responsive enzyme mimics are robust and stable under harsh conditions. They do not require special handling protocols like those for real enzymes and can be tailor-made for improved solubility in a variety of solvents. How the introduction of the light-responsive systems has offered a new-edge to the field of small-molecule enzyme mimic has been elaborated in this Mini-review. Recent breakthroughs in light-responsive enzyme-like systems have been highlighted. Finally, the current obstacles and future prospects of this field have been discussed.

Orthogonal‐ and Path‐Dependent Photo/Acidoswitching in an Eight‐State Dihydroazulene‐Spiropyran Dyad

AbstractMolecules comprised of two or more switches have potential to exist in a variety of states, which may only be accessible by a “correct” sequence of stimuli on account of the influence of the neighboring unit. Here we present a straightforward synthesis of a dyad incorporating two photoswitchable units, dihydroazulene (DHA) and spiropyran (SP). The photoswitching properties of both chromophores and the acido‐triggered switching of the SP were retained in the dyad, allowing selective switching between eight states with distinct absorption and fluorescence properties (corresponding to light‐controlled fluorescence on/off switching). Photoisomerization of DHA and protonation of SP allowed an orthogonal control of the individual sites. Conversely, photoisomerization of SP to its merocyanine (MC) isomer could not be performed without also addressing DHA‐to‐vinylheptafulvene (VHF) switching. Access to the DHA‐MC state thus appeared to be path‐dependent as it could exclusively be reached by deprotonation of the thermally stable DHA‐E‐MCH.

Light-Control over Casein Kinase 1δ Activity with Photopharmacology: A Clear Case for Arylazopyrazole-Based Inhibitors.

Protein kinases are responsible for healthy cellular processes and signalling pathways, and their dysfunction is the basis of many pathologies. There are numerous small molecule inhibitors of protein kinases that systemically regulate dysfunctional signalling processes. However, attaining selectivity in kinase inhibition within the complex human kinome is still a challenge that inspires unconventional approaches. One of those approaches is photopharmacology, which uses light-controlled bioactive molecules to selectively activate drugs only at the intended space and time, thereby avoiding side effects outside of the irradiated area. Still, in the context of kinase inhibition, photopharmacology has thus far been rather unsuccessful in providing light-controlled drugs. Here, we present the discovery and optimisation of a photoswitchable inhibitor of casein kinase 1δ (CK1δ), important for the control of cell differentiation, circadian rhythm, DNA repair, apoptosis, and numerous other signalling processes. Varying the position at which the light-responsive azobenzene moiety has been introduced into a known CK1δ inhibitor, LH846, revealed the preferred regioisomer for efficient photo-modulation of inhibitory activity, but the photoswitchable inhibitor suffered from sub-optimal (photo)chemical properties. Replacement of the bis-phenyl azobenzene group with the arylazopyrazole moiety yielded a superior photoswitch with very high photostationary state distributions, increased solubility and a 10-fold difference in activity between irradiated and thermally adapted samples. The reasons behind those findings are explored with molecular docking and molecular dynamics simulations. Results described here show how the evaluation of privileged molecular architecture, followed by the optimisation of the photoswitchable unit, is a valuable strategy for the challenging design of the photoswitchable kinase inhibitors.

Photochromic spiropyran-based liquid crystals

We present a new type of light responsive self-assembling structures based on a spiropyran photoswitchable unit. The spiropyran central part was modified by functional groups, which enabled the connection of two structurally different elongating parts. Two series of compounds were prepared with reversed orientation of the ester as a linkage group in the molecular core. The properties of the target materials were studied by differential scanning calorimetry and polarized light optical microscopy, which confirmed the presence of a nematic phase for most of the materials. In case of a trifluromethyl-substituted compound, a sequence of nematic – smectic A – smectic C phase was detected and confirmed by X-ray diffraction analysis. The photochromic properties of compounds were studied in solution as well as in mesophases. In the condensed state, UV light-induced switching from the spiropyran form to the merocyanine dye led to isothermal transition from the liquid crystalline phase to the isotropic liquid.

Quantitative Model for Reversibly Photoswitchable Sensors.

Composed of a reversibly photoswitchable unit allosterically linked to a sensing module, reversibly photoswitchable sensors (rs-sensors) represent a new and attractive strategy to quantitatively read-out analyte concentrations. However, their kinetic response to illumination is complex, and much attention is required from the design to the application steps. Here, we exploit a generic kinetic model of rs-sensors which enables us to point to key thermokinetic parameters, such as dissociation constants and kinetic rates for exchange toward the analyte, and cross-sections for photoswitching. The application of the model allows to evaluate the robustness of the analyzed parameters and to introduce a methodology for their reliable use. Model and methodology have been experimentally tested on a newly reported calcium sensor based on a reversibly photoswitchable green fluorescent protein allosterically linked to a calcium-sensing module integrating calmodulin and an RS20 peptide.

Fingerprinting the Excited-State Dynamics in Methyl Ester and Methyl Ether Anions of Deprotonated para-Coumaric Acid.

Chromophores based on the para-hydroxycinnamate moiety are widespread in the natural world, including as the photoswitching unit in photoactive yellow protein and as a sunscreen in the leaves of plants. Here, photodetachment action spectroscopy combined with frequency- and angle-resolved photoelectron imaging is used to fingerprint the excited-state dynamics over the first three bright action-absorption bands in the methyl ester anions (pCEs-) of deprotonated para-coumaric acid at a temperature of ∼300 K. The excited states associated with the action-absorption bands are classified as resonances because they are situated in the detachment continuum and are open to autodetachment. The frequency-resolved photoelectron spectrum for pCEs- indicates that all photon energies over the S1(ππ*) band lead to similar vibrational autodetachment dynamics. The S2(nπ*) band is Herzberg-Teller active and has comparable brightness to the higher lying 21(ππ*) band. The frequency-resolved photoelectron spectrum over the S2(nπ*) band indicates more efficient internal conversion to the S1(ππ*) state for photon energies resonant with the Franck-Condon modes (∼80%) compared with the Herzberg-Teller modes (∼60%). The third action-absorption band, which corresponds to excitation of the 21(ππ*) state, shows complex and photon energy-dependent dynamics, with 20-40% of photoexcited population internally converting to the S1(ππ*) state. There is also evidence for a mode-specific competition between prompt autodetachment and internal conversion on the red edge of the 21(ππ*) band. There is no evidence for recovery of the ground electronic state and statistical electron ejection (thermionic emission) following photoexcitation over any of the three action-absorption bands. The photoelectron spectra for the deprotonated methyl ether derivative (pCEt-) at photon energies over the S1(ππ*) and S2(nπ*) bands indicate diametrically opposed dynamics compared with pCEs-, namely, intense thermionic emission due to efficient recovery of the ground electronic state.

Enlightening Materials with Photoswitches.

Incorporating molecular photoswitches into various materials provides unique opportunities for controlling their properties and functions with high spatiotemporal resolution using remote optical stimuli. The great and largely still untapped potential of these photoresponsive systems has not yet been fully exploited due to the fundamental challenges in harnessing geometrical and electronic changes on the molecular level to modulate macroscopic and bulk material properties. Herein, progress made during the past decade in the field of photoswitchable materials is highlighted. After pointing to some general design principles, materials with an increasing order of the integrated photoswitchable units are discussed, spanning the range from amorphous settings over surfaces/interfaces and supramolecular ensembles, to liquid crystalline and crystalline phases. Finally, some potential future directions are pointed out in the conclusion. In view of the exciting recent achievements in the field, the future emergence and further development of light-driven and optically programmable (inter)active materials and systems are eagerly anticipated.

In Situ Observation of Photoswitching by NMR Spectroscopy: A Photochemical Analogue to the Exchange Spectroscopy Experiment.

We present 1D and 2D NMR experiments that provide in situ insights into photoinduced isomerizations. Irradiation during the mixing period of an exchange spectroscopy (EXSY) experiment leads to characteristic cross peaks in 2D spectra. The phototriggered exchange of magnetization occurring in photoswitchable (Z)- and (E)-isomers of three selected azo compounds provides information on the dynamic E/Z equilibria. We report the dependence of the diagonal-to-cross-peak ratio on concentration, light intensity, and mixing time. In analogy to exchange spectroscopy, this ratio mirrors the efficiency of light induced molecular transformations. Furthermore, we present a time-saving 1D version and a combined light/phase cycle scheme for enhanced detectability of photoinduced changes in the spectrum. This insight into light-induced structural changes is highly suited to study macromolecules, in which photoswitchable units trigger conformational changes.

An azobenzene container showing a definite folding - synthesis and structural investigation.

The combination of photo-switchable units with macrocycles is a very interesting field in supramolecular chemistry. Here, we present the synthesis of a foldable container consisting of two different types of Lissoclinum macrocyclic peptides which are connected via two azobenzene units. The container is controllable by light: irradiation with UV light causes a switching process to the compact cis,cis-isomer, whereas by the use of visible light the stretched trans,trans-isomer is formed. By means of quantum chemical calculations and CD spectroscopy we could show that the trans→cis isomerization is spatially directed; that means that one of the two different macrocycles performs a definite clockwise rotation to the other, caused by irradiation with UV light. For the cis→trans isomerization counterclockwise rotations are found. Furthermore, quantum chemical calculations reveal that the energy of the cis,cis-isomer is only slightly higher than the energy of the cis,trans-isomer. This effect can be explained by the high dispersion energy in the compact cis,cis-isomer.

Cover Feature: Isomerization Dynamics of Electronically Coupled but Thermodynamically Decoupled Bisazobenzenes (ChemPhotoChem 6/2019)

The Cover Feature illustrates the splitting of the isomerization pathways after selective excitation of a molecular double-photoswitch. Photoresponsive structures composed of multiple photoswitchable units offer the possibility of more diverse and complex control applications. For example, o-bisazobenzenes show unusual electronic coupling affecting the properties of the individual azobenzene units. Time-resolved spectroscopic experiments supported by quantum chemical calculations revealed that electronic coupling removes the bias introduced by selective excitation of one azobenzene moiety. More information can be found in the Article by C. Boumrifak et al. on page 411 in Issue 6, 2019 (DOI: 10.1002/cptc.201900077).

Isomerization Dynamics of Electronically Coupled but Thermodynamically Decoupled Bisazobenzenes

AbstractPhotoresponsive structures composed of multiple photoswitchable units offer the possibility of more diverse and complex control applications. For example, o‐bisazobenzenes (o‐bisABs) show unusual electronic coupling affecting the properties of the individual AB units. In the present work derivatives with amino and acetamido groups were investigated to gain further insight into the photoisomerization pathways of o‐bisABs. Time‐resolved spectroscopic experiments supported by quantum chemical calculations revealed that electronic coupling removes the bias introduced by selective excitation of one AB moiety. In effect, the isomerization ratio between the two photochromic units in o‐bisABs is intrinsically determined by the interplay of electronic coupling and their relative energy. Furthermore, the Z→E thermally activated relaxation of the AB moieties in o‐bisABs is decoupled and proceeds independently for each unit on different timescales.

Design and Synthesis of Metronidazole‐Based Photoswitches With Potential Biological Applications

AbstractPhotocontrol of the activity of biomolecules is a promising field to selectively target specific cells or tissues. Herein, we present a rational design of novel photoactive molecules which combine a metronidazole‐like moiety, responsible for the cytotoxic activity, and a photoswitchable unit. The proposed compounds stand out for their straightforward synthesis (two steps through a simple and versatile route), as well as their photochemical and thermal stability. These compounds are water soluble and their photoisomerization takes place with a high quantum yield. A computational study was performed to guide the design of this novel family, to fully characterize their structure and properties and to aid in the analysis of the experimental results. Moreover, the photoisomerized forms feature cytotoxicity in the micromolar range against human cancer cell lines, allowing a complete off/on photocontrol of the biological activity.

Bifunctional Cu2+/Fe3+ Probe with Independent Signal Outputs Based on a Photochromic Diarylethene with a Dansylhydrazine Unit.

A novel dual-response fluorescent sensor based on a diarylethene photoswitching unit and a dansylhydrazine functional group has been synthesized. The compound exhibited high selectivity for Fe3+ and Cu2+ with independent fluorescence signal outputs. In the presence of Fe3+, the sensor formed a 1:1 metal complex, resulting in a remarkable “turn-off” fluorescence signal. On the other hand, its fluorescence intensity was notably enhanced (turn-on) and a color change from bright yellow to bright blue was observed when the sensor interacted with Cu2+, which was due to the hydrolysis reaction of the dansyl acid dye, as confirmed by high-resolution mass spectrometry–electrospray ionization and infrared spectrum. The detection limits were 9.73 × 10–8 mol L–1 for Fe3+ and 3.49 × 10–7 mol L–1 for Cu2+, respectively. From the unimolecular platform, two molecular logic circuits were constructed using the fluorescence emission intensity at 557/494 nm (Fe3+/Cu2+) as the outputs and the combined stimuli of Fe3+/ethylenediaminetetraacetic acid, Cu2+, and UV/vis as the inputs. In addition, the sensor was successfully used to determine Fe3+ in water samples from Ganjiang River and soil samples from Nanchang fields.

On the use of diarylmaleimide derivatives in biological contexts: An investigation of the photochromic properties in aqueous solution

A series of photochromic diarylmaleimide derivatives has been synthesized and studied with respect to the photochromic properties in aqueous solution. The main rationale is to investigate if these compounds could be used as photoswitchable units in biological contexts, motivated by the fact that the diarylmaleimide structural motif is identified in many pharmacophores. Thus, photoswitchable variants of this class of compounds could be very useful in the quest for photoactivatable drugs. The photoinduced cyclization reaction (colorization) is suppressed in solvents of high polarity, whereas the ring-opening reaction (decolorization) still occurs with high efficiency. The photochromically active anti-parallel conformer of the open form is more abundant in the asymmetrically substituted derivatives, which in turn favors the formation of the closed isomeric form. The rates of the thermal isomerization reactions have also been assessed, together with the resistance toward thermal degradation. Here it was observed that the maleimide derived compounds were not susceptible to the thermally driven reactions (hydrolysis and isomerization).

Photocontrolled On-Surface Pseudorotaxane Formation with Well-Ordered Macrocycle Multilayers.

The photoinduced pseudorotaxane formation between a photoresponsive axle and a tetralactam macrocycle was investigated in solution and on glass surfaces with immobilized multilayers of macrocycles. In the course of this reaction, a novel photoswitchable binding station with azobenzene as the photoswitchable unit and diketopiperazine as the binding station was synthesized and studied by NMR and UV/Vis spectroscopy. Glass surfaces have been functionalized with pyridine-terminated SAMs and subsequently with multilayers of macrocycles through layer-by-layer self assembly. A preferred orientation of the macrocycles could be confirmed by NEXAFS spectroscopy. The photocontrolled deposition of the axle into the surface-bound macrocycle-multilayers was monitored by UV/Vis spectroscopy and led to an increase of the molecular order, as indicated by more substantial linear dichroism effects in angle-resolved NEXAFS spectra.