Zinc Oxide/Carbon Material-Embedded Supramolecular Drug Delivery System with Photoswitching Properties for Highly Selective and Effective Chemotherapy.

Phototherapy has become a hopeful procedure for the treatment of cancer. Nevertheless, the straightforward creation of a theranostic system that can achieve both tumor localization and production of oxygen species is greatly desired yet remains a challenging endeavor. In this study, we synthesized spherical nanostructures by decorating zinc oxide (ZnO) with peanut shell-based carbon (PNS-C) in an aqueous solution. The PNS-C-decorated ZnO (ZnO/PNS-C)-embedded supramolecular system exhibited spontaneous self-assembly. The nanogels that are produced have several desirable characteristics, including exceptional resistance to degradation by light, highly stable nanostructures that form spontaneously in biological environments, outstanding ability to prevent the destruction of red blood cells, and a high level of sensitivity to changes in pH and light. Under light irradiation, the addition of ZnO/PNS-C-incorporated supramolecular provided high reactive oxygen species production. Moreover, in vitro cellular assays demonstrated ZnO/PNS-C-incorporated supramolecular exhibited highly selective and induced phototoxicity into cancer cells and no effect on the viability of normal cells both before and after irradiation. Overall, the ZnO/PNS-C-incorporated supramolecular system has the potential to stimulate advancements in phototherapy by utilizing highly tumor-selective therapeutic molecules. This can lead to a more effective targeted therapy for cancers.

Reversible Light-Triggered Stretching of Small-Molecule Photochromic Organic Nanoparticles.

Functional organic nanomaterials are nowadays largely spread in the field of nanomedicine. In situ modulation of their morphology is thus expected to considerably impact their interactions with the surroundings. In this context, photoswitchable nanoparticles that are manufactured, amenable to extensive disassembling upon illumination in the visible, and reversible reshaping under UV exposure. Such reversibility turns to be strongly impaired for photochromic nanoparticles in close contact with a substrate. In situ atomic force microscopy investigations at the nanoscale actually reveal progressive disintegration of the organic nanoparticles under successive UV-vis cycles of irradiation, in the absence of intrinsic elastic forces. These results point out the dramatic interactions exerted by surfaces on the cohesion of non-covalently bonded organic nanoparticles. They invite to harness such systems, often used as biomarkers, to also serve as photoactivatable drug delivery nanocarriers.

Path-Independent All-Visible Orthogonal Photoswitching for Applications in Multi-Photochromic Polymers and Molecular Computing.

Synthetic molecular photoswitches have taken center stage as high-precision tools to introduce light-responsiveness at the smallest scales. Today they are found in all areas of applied chemistry, covering materials research, chemical biology, catalysis, or nanotechnology. For a next step of applicability truly orthogonal photoswitching is highly desirable but to date such independent addressability of different photoswitches remains to be highly challenging. In this work we present the first example of all-visible, all-light responsive, and path independent orthogonal photoswitching. By combining two recently developed indigoid photoswitches - peri-anthracenethioindigo and a rhodanine-based chromophore - a four-state system is established and each state can be accessed in high yields completely independently and also with visible light irradiation only. The four states give rise to four different colors, which can be transferred to a solid polymer matrix yielding a versatile multi-state photochromic material. Further, combination with a fluorescent dye as third component is possible, demonstrating applicability of this orthogonal photoswitching system in all-photonic molecular logic behavior and information processing.

Observation of a Picosecond Light-Induced Spin Transition in Polymeric Nanorods.

Spin transition (ST) materials are attractive for developing photoswitchable devices, but their slow material transformations limit device applications. Size reduction could enable faster switching, but the photoinduced dynamics at the nanoscale remains poorly understood. Here, we report a femtosecond optical pump multimodal X-ray probe study of polymeric nanorods. Simultaneously tracking the ST order parameter with X-ray emission spectroscopy and structure with X-ray diffraction, we observe photodoping of the low-spin-lattice within ∼150 fs. Above a ∼16% photodoping threshold, the transition to the high-spin phase occurs following an incubation period assigned to vibrational energy redistribution within the nanorods activating the molecular spin switching. Above ∼60% photodoping, the incubation period disappears, and the transition completes within ∼50 ps, preceded by the elastic nanorod expansion in response to the photodoping. These results support the feasibility of ST material-based GHz optical switching applications.

Arylazo-3,5-diphenylpyrazole Derivatives: Molecular Probes Exhibiting Reversible Light-induced Phase Transitions for Energy Storage and Direct Photolithographic Patterning.

We report azopyrazole photoswitches decorated with variable N-alkyl and alkoxy chains (for hydrophobic interactions) and phenyl substituents on the pyrazoles (enabling π-π stacking), showing efficient bidirectional photoswitching and reversible light-induced phase transition (LIPT). Extensive spectroscopic, microscopic, and diffraction studies and computations confirmed the manifestation of molecular-level interactions and photoisomerization into macroscopic changes leading to the LIPT phenomena. Using differential scanning calorimetric (DSC) studies, the energetics associated with those accompanying processes were estimated. The long half-lives of Z isomers, high energy contents for isomerization and phase transitions, and the stability of phases over an extended temperature range (-60 to 80 oC) make them excellent candidates for energy storage and release applications. Remarkably, the difference in the solubility of the distinct phases in one of the derivatives allowed us to utilize it as a photoresist in photolithography applications on diverse substrates.

Azopyridinium Ionic Photoswitches: Tuning Half-lives of Z Isomers from Seconds to Days in Water.

Herein, we describe water-soluble heteroaryl azopyridinium ionic photoswitches (HAPIPs). We aim to combine variations in five-membered heterocycles, their substitutions, N-alkyl groups at pyridinium nitrogen, the position of pyridinium center relative to azo group, counterions, and solvents, in achieving better photoswitching. Through these studies, we successfully tuned the half-life of Z isomers of the resultant HAPIPs between seconds to days in water. Extensive spectroscopic studies and density functional theory (DFT) computations unravelled the factors responsible for thermal relaxation behavior. Considering the versatility of these photoswitches, the tunability of half-lives and photoswitching in aqueous medium allows the scope of applications in several fields.

Photoswitching Reagent for Super-Resolution Fluorescence Microscopy.

Single-molecule localization microscopy (SMLM) has revolutionized optical microscopy by exceeding the diffraction limit and revealing previously unattainable nanoscale details of cellular structures and molecular dynamics. This super-resolution imaging capability relies on fluorophore photoswitching, which is crucial for optimizing the imaging conditions and accurately determining the fluorophore positions. To understand the general on and off photoswitching mechanisms of single dye molecules, various photoswitching reagents were evaluated. Systematic measurement of the single-molecule-level fluorescence on and off rates (kon and koff) in the presence of various photoswitching reagents and theoretical calculation of the structure of the photoswitching reagent-fluorophore pair indicated that the switch-off mechanism is mainly determined by the nucleophilicity of the photoswitching reagent, and the switch-on mechanism is a two-photon-induced dissociation process, which is related to the power of the illuminating laser and bond dissociation energy of this pair. This study contributes to a broader understanding of the molecular photoswitching mechanism in SMLM imaging and provides a basis for designing improved photoswitching reagents with potential applications extending to materials science and chemistry.

The role of the correlated motion(s) of the chromophore in photoswitching of green and red forms of the photoconvertible fluorescent protein mSAASoti.

Wild-type SAASoti and its monomeric variant mSAASoti can undergo phototransformations, including reversible photoswitching of the green form to a nonfluorescent state and irreversible green-to-red photoconversion. In this study, we extend the photochemistry of mSAASoti variants to enable reversible photoswitching of the red form. This result is achieved by rational and site-saturated mutagenesis of the M163 and F177 residues. In the case of mSAASoti it is M163T substitution that leads to the fastest switching and the most photostable variant, and reversible photoswitching can be observed for both green and red forms when expressed in eukaryotic cells. We obtained a 13-fold increase in the switching efficiency with the maximum switching contrast of the green form and the appearance of comparable switching of the red form for the C21N/M163T mSAASoti variant. The crystal structure of the C21N mSAASoti in its green on-state was obtained for the first time at 3.0 Å resolution, and it is in good agreement with previously calculated 3D-model. Dynamic network analysis reveals that efficient photoswitching occurs if motions of the 66H residue and phenyl fragment of chromophore are correlated and these moieties belong to the same community.

Structure-property relationship in functionalized azobenzene photoswitches and their supramolecular behavior.

Herein, we report the design, synthesis, and supramolecular behavior of 30 structurally diverse photoresponsive azobenzene molecular systems. To establish structure-property relationships, azobenzenes appended with N-picolinyl and/or N-benzyl groups tethered directly through carboxamides or via triazolylmethyl carboxamide linkages were explored. We have evaluated the photoswitching characteristics and thermal stability of the Z isomers through systematic studies. All the targets were also screened for their aggregation behavior and supramolecular aspects. Among all the derivatives, a few carboxamide-based systems formed microcrystals upon aggregation, showing light responsiveness. In contrast, the derivatives tethered via triazolylmethyl carboxamide linkage exhibited hydrogel formation with excellent water-absorbing capacity. All supramolecular aspects of the morphology of the microcrystal and hydrogel states and their stimuli-responsiveness have been studied using spectroscopy and various microscopic techniques.

Orthogonal Photoswitching in a Porous Organic Framework.

The development of photoresponsive systems with non-invasive orthogonal control by distinct wavelengths of light is still in its infancy. In particular, the design of photochemically triggered-orthogonal systems integrated into solid materials that enable multiple dynamic control over their properties remains a longstanding challenge. Here, we report the orthogonal and reversible control of two types of photoswitches in an integrated solid porous framework, that is, visible-light responsive o-fluoroazobenzene and nitro-spiropyran motifs. The properties of the constructed material can be selectively controlled by different wavelengths of light thus generating four distinct states providing a basis for dynamic multifunctional materials. Solid-state NMR spectroscopy demonstrated the selective transformation of the azobenzene switch in the bulk, which in turn modulates N2 and CO2 adsorption.

Robust Red-Absorbing Donor-Acceptor Stenhouse Adduct Photoswitches.

Donor-Acceptor Stenhouse Adduct (DASA), a class of push-pull negative photochrome, has received large interest lately owing to its versatile synthesis, modularity and excellent photoswitching in solutions. From a technological perspective, it is imperative for this class of photoswitches to work robustly in solid state, e. g. thin films. We feature a molecular framework for the optimized design of DASAs by introducing a new thioindoline donor (D3) and assessing its performance against known 2nd generation indoline-based donors. The systematic structure-function investigations suggest that to achieve robust reversible photoswitching, a ground state with low charge separation is desired. DASAs with stronger electron donors and a larger charge separation in the ground state result in a low population of the photothermalstationary state (PTSS) and reduced photostability. The DASA with thioindoline donor (D3A3) seems to be a special case among the donor series as it causes a red shift (ca. 15 nm), however with less polarization of the ground state and marginally better photostability as compared to the unsubstituted 2-methyl indoline (D1A3). We also emphasize the consideration of the key additional factors that can modulate the red-light photoswitching properties of DASA chromophores in polymer thin films, which might not be dominant in homogenous solution state.

Visible-Light-Sensitive Photoliquefiable Arylazoisoxazoles for the Solar Energy Conversion, Storage and Controlled-Release of Heat at Room Temperature or Lower Temperatures.

The photoswitchable MOlecular Solar Thermal (MOST) energy storage systems that are capable of exhibiting high energy storage densities are found to suffer from the poor cyclability, the use of less abundant UV light of the solar spectrum, or reduced charging/discharging rates and poor photoconversions in solid states. Herein, we have designed and readily synthesized a novel set of para-thioalkyl substituted arylazoisoxazoles, that undergo high trans-cis and cis-trans photoconversions under visible light, and show fast charging/discharging and impressive cyclability. Remarkably, the presence of C6-or C10-thioalkyl chainin photochromes permitted reversible solid-liquid phase transition with the formation of cis-enriched charged states by 400 nm light irradiation and trans-enriched discharged states by 530 nm light at various temperatures (10-35 °C). The solid-to-liquid phase transition enabled storage of the latent heat in addition to the isomerization energy, resulting in a high net energy storage density of 189-196 J/g, which are substantially higher than that of many recently reported azobenzene-based MOST compounds (100-161 J/g). Using a high-resolution infrared camera, we further demonstrated that a brief irradiation of green light can be employed to readily release the trapped photon energy as heat. Our results suggest that the arylazoisoxazole with C6-thioalkyl chain at para-position can serve as an effective and eco-friendly photoliquefiable MOST material.

Photochromic derivatives of indigo: historical overview of development, challenges and applications.

The importance of indigo dyes is constantly increasing with the evolution of novel textile materials and photochromic material technologies. The aim of this review article is to provide a comprehensive overview of the development of photochromic indigo derivatives from the first report on the photochromic N,N'-diacetylindigo in 1954 until now. We begin with the list of historical milestones in the development of photochromic indigo derivatives. Further, we provide a brief description of the synthetic procedures utilised to obtain indigo and its derivatives, outline the structural peculiarities, photophysical and photochemical properties of indigo and proceed with the detailed discussion of the photochromic indigo derivatives. Finally, we highlight the photochromism of the structural isomers of indigo (isoindigo and indirubin) and provide an overview of prospective applications of indigo photoswitches.

Photoswitching in a Liquid Crystalline Pt(II) Coordination Complex.

Photoswitching of photoluminescence has sparked tremendous research interests for super-resolution imaging, high-security-level anti-counterfeiting, and other high-tech applications. However, the excitation of photoluminescence is usually ready to trigger the photoswitching process, making the photoluminescence readout unreliable. Herein, we report a new photoswitch by the marriage of spiropyran with platinum(II) coordination complex. Viable photoluminescence can be achieved upon excitation by 480 nm visible light while the photoswitching can be easily triggered by 365 nm UV light. The feasible photoswitching may be benefited from the formed liquid crystalline (LC) phase of the designed photoswitch as a crystalline spiropyran is normally unable to implement photoswitching. Compared to the counterparts, this LC photoswitch can show distinct and reliable apparent colors and emission colors before and after photoswitching, which may promise the utility in high-security-level anti-counterfeiting and other advanced information technologies.

Revisiting Peri-Aryloxyquinones: From a Forgotten Photochromic System to a Promising Tool for Emerging Applications.

Emerging applications of photochromic compounds demand new molecular designs that can be inspired by some long-known yet currently forgotten classes of photoswitches. In the present review, we remind the community about Peri-AryloxyQuinones (PAQs) and their unique photoswitching behavior originally discovered more than 50 years ago. At the heart of this phenomenon is the light-induced migration of an aromatic moiety (arylotropy) in peri-aryloxy-substituted quinones resulting in ana-quinones. PAQs feature absorbance of both isomers in the visible spectral region, photochromism in the amorphous and crystalline state, and thermal stability of the photogenerated ana-isomer. Particularly noticeable is the high sensitivity of the ana-isomer towards nucleophiles in solution. In addition to the mechanism of molecular photochromism and the underlaying structure-switch relationships, we analyze potential applications and prospects of aryloxyquinones in optically switchable materials and devices. Due to their ability to efficiently photoswitch in the solid state, PAQs are indeed attractive candidates for such materials and devices, including electronics (optically controllable circuits, switches, transistors, memories, and displays), porous crystalline materials, crystalline actuators, photoactivated sensors, and many more. This review is intended to serve as a guide for researchers who wish to use photoswitchable PAQs in the development of new photocontrollable materials, devices, and processes.

Photo-Controlled Gating of Selective Bacterial Membrane Interaction and Enhanced Antibacterial Activity for Wound Healing.

Reversible biointerfaces are essential for on-demand molecular recognition to regulate stimuli-responsive bioactivity such as specific interactions with cell membranes. The reversibility on a single platform allows the smart material to kill pathogens or attach/detach cells. Herein, we introduce a 2D-MoS2 functionalized with cationic azobenzene that interacts selectively with either Gram-positive or Gram-negative bacteria in a light-gated fashion. The trans conformation (trans-Azo-MoS2 ) selectively kills Gram-negative bacteria, whereas the cis form (cis-Azo-MoS2 ), under UV light, exhibits antibacterial activity against Gram-positive strains. The mechanistic investigation indicates that the cis-Azo-MoS2 exhibits higher affinity towards the membrane of Gram-positive bacteria compared to trans-Azo-MoS2 . In case of Gram-negative bacteria, trans-Azo-MoS2 internalizes more efficiently than cis-Azo-MoS2 and generates intracellular ROS to kill the bacteria. While the trans-Azo-MoS2 exhibits strong electrostatic interactions and internalizes faster into Gram-negative bacterial cells, cis-Azo-MoS2 primarily interacts with Gram-positive bacteria through hydrophobic and H-bonding interactions. The difference in molecular mechanism leads to photo-controlled Gram-selectivity and enhanced antibacterial activity. We found strain-specific and high bactericidal activity (minimal bactericidal concentration, 0.65 µg/ml) with low cytotoxicity, which we extended to wound healing applications. This methodology provides a single platform for efficiently switching between conformers to reversibly control the strain-selective bactericidal activity regulated by light.

Compact Micropatterned Chip Empowers Undisturbed and Programmable Drug Addition in High-Throughput Cell Screening.

Simultaneously adding multiple drugs and other chemical reagents to individual droplets at specific time points presents a significant challenge, particularly when dealing with tiny droplets in high-throughput screening applications. In this study, a micropatterned polymer chip is developed as a miniaturized platform for light-induced programmable drug addition in cell-based screening. This chip incorporates a porous superhydrophobic polymer film with atom transfer radical polymerization reactivity, facilitating the efficient grafting of azobenzene methacrylate, a photoconformationally changeable group, onto the hydrophilic regions of polymer matrix at targeted locations and with precise densities. By employing light irradiation, the cyclodextrin-azobenzene host-guest complexes formed on the polymer chip can switch from an "associated" to a "dissociated" state, granting precise photochemical control over the supramolecular coding system and its surface patterning ability. Significantly, the exceptional spatial and temporal control offered by these chemical transitions empowers to utilize digital light processing systems for simultaneous regulation and release of cyclodextrin-bearing drugs across numerous droplets containing suspended or adhered cells. This approach minimizes mechanical disruption while achieving precise control over the timing of addition, dosage, and integration varieties of released drugs in high-throughput screening, all programmable to meet specific requirements.

Manipulating Surface Band Bending of III-Nitride Nanowires with Ambipolar Charge-Transfer Characteristics: A Pathway Toward Advanced Photoswitching Logic Gates and Encrypted Optical Communication.

The operational principle of semiconductor devices critically relies on the band structures that ultimately govern their charge-transfer characteristics. Indeed, the precise orchestration of band structure within semiconductor devices, notably at the semiconductor surface and corresponding interface, continues to pose a perennial conundrum. Herein, for the first time, this work reports a novel postepitaxy method: thickness-tunable carbon layer decoration to continuously manipulate the surface band bending of III-nitride semiconductors. Specifically, the surface band bending of p-type aluminum-gallium-nitride (p-AlGaN) nanowires grown on n-Si can be precisely controlled by depositing different carbon layers as guided by theoretical calculations, which eventually regulate the ambipolar charge-transfer behavior between the p-AlGaN/electrolyte and p-AlGaN/n-Si interface in an electrolyte environment. Enabled by the accurate modulation of the thickness of carbon layers, a spectrally distinctive bipolar photoresponse with a controllable polarity-switching-point over a wide spectrum range can be achieved, further demonstrating reprogrammable photoswitching logic gates "XOR", "NAND", "OR", and "NOT" in a single device. Finally, this work constructs a secured image transmission system where the optical signals are encrypted through the "XOR" logic operations. The proposed continuous surface band tuning strategy provides an effective avenue for the development of multifunctional integrated-photonics systems implemented with nanophotonics.

A Visible Light Responsive Smart Covalent Organic Framework with a Bridged Azobenzene Backbone.

Condensation of 3,3'-diamino-2,2'-ethylene-bridged azobenzene with 1,2,4,5-tetrakis-(4-formylphenyl) benzene produces a visible light responsive porous 2D covalent organic framework, COF-bAzo-TFPB, with a large surface area, good crystallinity, and thermal and chemical stability. The results demonstrate that the elaborated designed linker can make azo unit on the COF-bAzo-TFPB skeleton undergo reversible photoisomerization. This work expands the application scope of covalent organic frameworks in photo-controlled release, uptake of guest molecules, dynamic photoswitching, and UV-sensitive functions.

Photoswitching alters fluorescence readout of jGCaMP8 Ca2+ indicators tethered to Orai1 channels.

We used electrophysiology and Ca2+ channel tethering to evaluate the performance of jGCaMP8 genetically encoded Ca2+ indicators (GECIs). Orai1 Ca2+ channel-jGCaMP8 fusions were transfected into HEK 293A cells and jGCaMP8 fluorescence responses recorded by simultaneous total internal reflection fluorescence microscopy and whole-cell patch clamp electrophysiology. Noninactivating currents from the Orai1 Y80E mutant provided a steady flux of Ca2+ controlled on a millisecond time scale by step changes in membrane potential. Test pulses to -100 mV produced Orai1 Y80E-jGCaMP8f fluorescence traces that unexpectedly declined by ~50% over 100 ms before reaching a stable plateau. Testing of Orai1-jGCaMP8f using unroofed cells further demonstrated that rapid and partial fluorescence inactivation is a property of the indicator itself, rather than channel function. Photoinactivation spontaneously recovered over 5 min in the dark, and recovery was accelerated in the absence of Ca2+. Mutational analysis of residues near the tripeptide fluorophore of jGCaMP8f pointed to a mechanism: Q69M/C70V greatly increased (~90%) photoinactivation, reminiscent of fluorescent protein fluorophore cis-trans photoswitching. Indeed, 405-nm illumination of jGCaMP8f or 8m/8s/6f led to immediate photorecovery, and simultaneous illumination with 405 and 488-nm light blocked photoinactivation. Subsequent mutagenesis produced a variant, V203Y, that lacks photoinactivation but largely preserves the desirable properties of jGCaMP8f. Our results point to caution in interpreting rapidly changing Ca2+ signals using jGCaMP8 and earlier series GECIs, suggest strategies to avoid photoswitching, and serve as a starting point to produce more photostable, and thus more accurate, GECI derivatives.