Photocontrolled Binding of Styrylnaphthyridine Ligands to Abasic Site-Containing DNA by Reversible [2+2] Cycloaddition and Cycloreversion.

Five novel styrylnaphthyridine derivatives were synthesized and shown to operate as photoswitchable, selective ligands for abasic site-containing DNA (AP-DNA), which is an important therapeutic and diagnostic target. These compounds associate with AP-DNA with binding constants of 0.5-8.4×104 M-1 as shown by photometric and fluorimetric titrations. Specifically, these ligands bind preferentially to AP-DNA relative to regularly paired duplex DNA. As a special feature, the association of these ligands with DNA can be controlled by means of a reversible [2+2] photocycloaddition. Upon irradiation at 420 nm the photodimer is formed, which does not bind to AP-DNA. In turn, the naphthyridine is regained with excitation at 315 nm. Most notably, this photoinduced deactivation and release of the DNA ligand can be performed in situ in the presence of AP-DNA, thus providing a tool for on-demand delivery of a DNA binder. Overall, these results provide a promising starting point for the development of functional AP-DNA ligands whose bioactivity can be modulated by light with local and temporal control.

Visible-Light-Mediated [2+2] Photocycloadditions of Alkynes.

Visible-light-mediated [2+2] photocycloaddition reaction can be considered an ideal solution due to its green and sustainable properties, and is one of the most efficient methods to synthesize four-membered ring motifs. Although research on the [2+2] photocycloaddition of alkynes is challenging because of the diminished reactivity of alkynes, and the more significant ring strain of the products, remarkable achievements have been made in this field. In this article, we highlight the recent advances in visible-light-mediated [2+2] photocycloaddition reactions of alkynes, with focus on the reaction mechanism and the late-stage synthetic applications. Advances in obtaining cyclobutenes, azetines, and oxetene active intermediates continue to be breakthroughs in this fascinating field of research.

Intramolecular [π4s + π4s] photocycloaddition of carbon- and nitrogen-bridged [32](1,4)naphthalenophanes.

[32](1,4)Naphthalenophanes, bearing carbon-bridge chains (syn- and anti-NPs) and nitrogen-bridge chains (syn- and anti-ANPs), were synthesized, and their X-ray structures and photoreactions were investigated. The intramolecular separation distance between the naphthalene cores for ANPs was shorter than that for NPs, suggesting that intramolecular interactions between the naphthalene rings  were more efficient for ANPs compared to NPs. Upon photoirradiation at 300 nm, anti-NP, syn-ANP and anti-ANP produced the corresponding intramolecular [π4s + π4s] cycloadducts, whereas syn-NP gave an unidentified complex product mixture. Quantum yields for the photo-consumption (ΦPC) of NPs and ANPs were evaluated to quantitatively compare their photoreactivity. The ΦPC values of ANPs were approximately two-fold higher than those of ANPs.Noteworthily, the ΦPC value of syn-ANP was estimated to be unity. Based on these results we discuss the effects of the alignments of the naphthalene cores (anti vs. syn) and the bridging elements (C-bridge vs. N-bridge) on the photoreaction efficiencies of [32](1,4)naphthalenophanes.

Harnessing the Photoperformance of N-Methyl-Quinolinone for Gated Photo-Driven Cyclability and Reversible Photoligation.

[2π + 2π]-photocycloadditions and their ability to trigger controlled and reversible photoligation through disparate wavelengths provide an attractive platform to unlock advanced functionalities in soft materials. Yet, among the limited amount of functional motifs enabling reversible photoreactions, cyclability is often overlooked due to poor reaction yield and orthogonality. In this study, the advantageous photocharacteristics of the previously underexplored N-methyl-quinolinone photoresponsive motif are leveraged to create a covalent gated system, enabling controlled formation and cleavage of covalent bonds on demand. A systematic evaluation of individual cycloadditions and reversions on the molecular scale, including reaction rates, conversions, and photoproducts, allows identification of the required conditions for generating controlled photoreactions with a remarkable degree of cyclability; while, maintaining high reaction yields. Ultimately, these controlled and cyclable reactions are translated to a macromolecular scale, showcasing a comparable performance in initiating reversible photoligation, as observed at the molecular level. In addition, it is also shown that this progressive methodology can be leveraged to gain a comprehensive understanding of cyclability and clarify the factors contributing to its decreasing yield. Overall, unlocking the potential of quinolinone derivatives through this step-by-step approach lays the foundation for the development of highly controlled and responsive polymer materials with unprecedented potential.

Cyclodextrin 'Chaperones' Enable Quasi-Ideal Supramolecular Network Formation and Enhanced Photodimerization of Hydrophobic, Red-shifted Photoswitches in Water.

Precision-engineered light-triggered hydrogels are important for a diversity of applications. However, fields such as biomaterials require wavelength outside the harsh UV regime to prevent photodamage, typically requiring chromophores with extended π-conjugation that suffer from poor water solubility. Herein, we demonstrate how cyclodextrins can be used as auxiliary agents to not only solubilize such chromophores, but even to preorganize them in a 2 : 2 host-guest inclusion complex to facilitate photodimerization. We apply our concept to styrylpyrene-end-functionalized star-shaped polyethylene glycols (sPEGs). We initially unravel details of the host-guest inclusion complex using spectroscopy and mass spectrometry to give clear evidence of a 2 : 2 complex formation. Subsequently, we show that the resultant supramolecularly linked hydrogels conform to theories of supramolecular quasi-ideal model networks, and derive details on their association dynamics using in-depth rheological measurements and kinetic models. By comparing sPEGs of different arm length, we further elucidate the model network topology and the accessible mechanical property space. The photo-mediated dimerization proceeds smoothly, allowing to transform the supramolecular model networks into covalent ones. We submit that our strategy opens avenues for executing hydrophobic photochemistry in aqueous environments with enhanced control over reactivity, hydrogel topology or programmable mechanical properties.

Catalytic Asymmetric Redox-Neutral [3+2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer.

Consecutive photoinduced electron transfer (ConPET) is a powerful and atom-economical protocol to overcome the limitations of the intrinsic redox potential of visible light-absorbing photosensitizers, thereby considerably improving the substrate and reaction types. Likely because such an exothermic single-electron transfer (SET) process usually does not require the aid of chiral catalysts, resulting in an inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on the viability of cooperative ConPET and chiral hydrogen-bonding catalysis for the [3+2] photocycloaddition of cyclopropyl ketones with vinylazaarenes. In addition to enabling the first use of olefins that preferentially interact with chiral catalysts, this catalysis platform paves the way for the efficient synthesis of pharmaceutically and synthetically important cyclopentyl ketones functionalized by azaarenes with high yields, ees and dr. The robust capacity of the method can be further highlighted by the low loading of the chiral catalyst (1.0 mol %), the good compatibility of both 2-azaarene and 3-pyridine-based olefins, and the successful concurrent construction of three stereocenters on cyclopentane rings involving an elusive but important all-carbon quaternary.

Visible Light-Responsive Crystalline B←N Host Adducts with Solvent-Induced Allosteric Effect for Guest Release.

Photo-responsive organic crystals, capable of converting light energy into chemical energy to initiate conformational transitions, present an emerging strategy for developing lightweight and versatile smart materials. However, visible light-triggered tailored guests capture and release behaviors in all-organic solids are rarely reported. Here, we introduce a photoreactive crystalline boron-nitrogen (B←N) host adduct with the ability to undergo [2+2] photocycloaddition upon 447 nm light exposure. This process facilitates single-crystal-to-single-crystal (SCSC) photodimerization in the mother liquor, maintaining the original B←N host structure. Weakened intermolecular interactions within the photodimer host contribute to fast guest release in air under irradiation. Furthermore, the dynamic B←N bonds enable reversible transformations between organic host adducts and adduct cocrystals under the solvent-induced allosteric effect. As a result, four B←N host adduct crystals containing individual alkane guest are easily obtained and exhibited the ability of photo-controlled alkane release. Therefore, the integration of photo reactivity and structural transformation within B←N host adduct enables customized capture and release of guest molecules.

Dearomative Construction of 2D/3D Frameworks from Quinolines via Nucleophilic Addition/Borate-Mediated Photocycloaddition.

Dearomative construction of multiply-fused 2D/3D frameworks, composed of aromatic two-dimensional (2D) rings and saturated three-dimensional (3D) rings, from readily available quinolines has greatly contributed to drug discovery. However, dearomative cycloadditions of quinolines in the presence of photocatalysts usually afford 5,6,7,8-tetrahydroquinoline (THQ)-based polycycles, and dearomative access to 1,2,3,4-THQ-based structures remains limited. Herein, we present a chemo-, regio-, diastereo-, and enantioselective dearomative transformation of quinolines into 1,2,3,4-THQ-based 6-6-4-membered rings without any catalyst, through a combination of nucleophilic addition and borate-mediated [2+2] photocycloaddition. Detailed mechanistic studies revealed that the photoexcited borate complex, generated from quinoline, organolithium, and HB(pin), accelerates the cycloaddition and suppresses the rearomatization that usually occurs in conventional photocycloaddition. Based on our mechanistic analysis, we also developed further photoinduced cycloadditions affording other types of 2D/3D frameworks from isoquinoline and phenanthrene.

The Use of Photocycloaddition Reactions to Drive Mechanical Motions Resembling Humanoid Movements.

With the aim of producing a photomechanical material for incorporation in soft microrobots, a one-dimensional diene coordination polymer (CP) [Cd(F-bpeb)(3-CBA)2]n (CP1, F-bpeb=4,4'-((1E,1'E)-(2,5-difluoro-1,4-phenylene)bis(ethene-2,1-diyl))dipyridine, 3-HCBA=3-chlorobenzoic acid) was synthesized and characterized. Irradiation of CP1 with ultraviolet (UV) or visible light causes [2+2] photocycloaddition reactions resulting in the introduction of crystal strain which triggers various types of crystal movements. Composite films of CP1-PVA (SC) fabricated by dispersing CP1 crystals into polyvinyl alcohol (PVA) solution allow amplification of the crystal movement so that the film strips exhibit fast and flexible curling upon photoirradiation. The composite films may be cut into long rectangular strips and folded to simulate soft microrobots which exhibit a variety of fast, flexible and continuous photomechanical movements resembling a human performing various gymnastic exercises.

Light and Guest Responsive Behavior in a Porous Coordination Network Enabled by Reversible [2+2] Photocycloaddition.

Stimuli-responsive physisorbents that undergo reversible structural transformations induced by external stimuli (e.g. light, guests, or heat) offer the promise of utility in gas storage and separation. Whereas reports on guest or light-responsive sorbents have increased in recent years, we are unaware of reports on sorbents that exhibit both light and guest-induced structural transformations. Herein, we report that the square lattice, sql, topology coordination network Zn(fba)(bis) ⋅ 2DMF (sql-5,6-Zn-α, 5=trans-4,4'-bis(1-imidazolyl)stilbene=bis, 6=2,2-bis(4-carboxyphenyl)hexafluoropropane=H2fba) underwent single-crystal-to-single-crystal transformation (SCSC) upon activation, affording nonporous sql-5,6-Zn-ß. Parallel alignment at 3.23 Šof olefinic moieties on adjacent bis ligands in sql-5,6-Zn-α enabled SCSC [2+2] photocycloaddition upon exposure to UV light (365 nm) or sunlight. sql-5,6-Zn-α thereby transformed to mot-5,6-Zn-α, which was subsequently activated to the narrow pore phase mot-5,6-Zn-ß. sql-5,6-Zn-ß and mot-5,6-Zn-ß both exhibited S-shaped adsorption isotherms characteristic of guest-induced structural changes when exposed to CO2 at 195 K (type-F-IV and type F-I, respectively). Cycling experiments conducted upon sql-5,6-Zn-ß reduced particle size after cycle 1 and induced transformation into a rare example of a shape memory coordination network, sql-5,6-Zn-γ. Insight into this smorgasbord of SCSC phase changes was gained from in situ PXRD, single crystal XRD and 1H NMR spectroscopy experiments.

Precision Nanocluster-Based Toroidal and Supertoroidal Frameworks Using Photocycloaddition-Assisted Dynamic Covalent Chemistry.

Atomically precise nanoclusters (NCs) have recently emerged as ideal building blocks for constructing self-assembled multifunctional superstructures. The existing structures are based on various non-covalent interactions of the ligands on the NC surface, resulting in inter-NC interactions. Despite recent demonstrations on light-induced reversible self-assembly, long-range reversible self-assembly based on dynamic covalent chemistry on the NC surface has yet to be investigated. Here, it is shown that Au25 NCs containing thiolated umbelliferone (7-hydroxycoumarin) ligands allow [2+2] photocycloaddition reaction-induced self-assembly into colloidal-level toroids. The toroids upon further irradiation undergo inter-toroidal reaction resulting in macroscopic supertoroidal honey-comb frameworks. Systematic investigation using electron microscopy, atomic force microscopy (AFM), and electron tomography (ET) suggest that the NCs initially form spherical aggregates. The spherical structures further undergo fusion resulting in toroid formation. Finally, the toroids fuse into macroscopic honeycomb frameworks. As a proof-of-concept, a cross-photocycloaddition reaction between coumarin-tethered NCs and an anticancer drug (5-fluorouracil) is demonstrated as a model photo-controlled drug release system. The model system allows systematic loading and unloading of the drug during the assembly and disassembly under two different wavelengths. The results suggest that the dynamic covalent chemistry on the NC surface offers a facile route for hierarchical multifunctional frameworks and photocontrolled drug release.

Photoactivation of Solid-State Fluorescence through Controllable Intermolecular [2+2] Photodimerization.

Intermolecular [2+2] photodimerization provides a distinctive approach to construct photoresponsive fluorescent materials in a manner of switching on solid-state fluorescence. Herein, we report efficient photoactivation of bright solid-state fluorescence based on controllable intermolecular [2+2] photodimerization reaction of benzo[b]thiophene 1,1-dioxide (BTO) derivatives, which provides a simple and effective way to construct smart photoresponsive solid-state fluorescent materials. Rational choice of substituents in BTO molecular skeleton enables them to efficiently undergo photodimerization through regulating molecular stacking in crystal, and also leads to photoactivation of solid-state fluorescence due to the generation of brightly fluorescent photodimers. This intermolecular photodimerization reaction also offers an effective method to synthesize photostable AIEgens with purely through-space conjugation.

Visible-Light-Mediated Catalyst-Free [2+2] Cycloaddition Reaction for Dihydrocyclobuta[b]naphthalene-3,8-diones Synthesis under Mild Conditions.

A facile and efficient visible-light-mediated method for directly converting 1,4-naphthoquinones into dihydrocyclo-buta[b]naphthalene-3,8-diones (DHCBNDOs) under mild and clean conditions without using any photocatalysts is reported. This approach exhibited favorable compatibility with functional groups and afforded a series of DHCBNDOs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Visible Light and Microwave-Mediated Rapid Trapping and Release of Singlet Oxygen Using a Coordination Polymer.

Due to its high reactivity and oxidative strength, singlet oxygen (1 O2 ) is used in a variety of fields including organic synthesis, biomedicine, photodynamic therapy and materials science. Despite its importance, the controlled trapping and release of 1 O2 is extremely challenging. Herein, we describe a one-dimensional coordination polymer, CP1, which upon irradiation with visible light, transforms 3 O2 (triplet oxygen) to 1 O2 . CP1 consists of CdII centers bridged by 9,10-bis((E)-2-(pyridin-4-yl)vinyl)anthracene ligands which undergo a [4+2] cycloaddition reaction with 1 O2 , resulting in the generation of CP1-1 O2 . Using microwave irradiation, CP1-1 O2 displays efficient release of 1 O2 , over a period of 30 s. In addition, CP1 exhibits enhanced fluorescence and has an oxygen detection limit of 97.4 ppm. Theoretical calculations reveal that the fluorescence behaviour is dominated by unique through-space conjugation. In addition to describing a highly efficient approach for the trapping and controlled release of 1 O2 , using coordination polymers, this work also provides encouragement for the development of efficient fluorescent oxygen sensors.

Photo-responsive Single-Molecule Magnet Showing 0D to 1D Single-Crystal-to-Single-Crystal Structural Transition and Hysteresis Modulation.

Photo-responsive lanthanide-based single-molecule magnets (SMM) hold great promise for future switching and memory devices. Herein, we report a dysprosium phosphonate [DyIII (SCN)2 (NO3 )(depma)2 (4-hpy)2 ] (1Dy), which features a supramolecular framework containing layers of hydrogen-bonding network and pillars of π-π interacted anthracene units. The photocycloaddition reaction of anthracene pairs led to a rapid and reversible single-crystal-to-single-crystal (SC-SC) structural transition to form the 1D coordination polymer [DyIII (SCN)2 (NO3 )(depma2 )(4-hpy)2 ]n (2Dy), accompanied by photoswitchable SMM properties with the reduction of effective energy barrier by half and the narrowing of the butterfly-like hysteresis loop. The diluted sample showed a photo-induced switch of the blocking temperature (TB ) from 3.8 K for 1Dy@Y to 2.6 K for 2Dy@Y. This work may inspire the construction of lanthanide-based molecular materials with targeted photo-responsive magnetic properties.

Phase Transition-Promoted Rapid Photomechanical Motions of Single Crystals of a Triene Coordination Polymer.

Molecular crystals with the ability to transform light energy into macroscopic mechanical motions are a promising class of materials with potential applications in actuating and photonic devices. In regard to such materials, coordination polymers that exhibit dynamic photomechanical motion, associated with a phase transition, are unknown. Herein, we report an intriguing photoactive, one-dimensional ZnII coordination polymer, 1, derived from 1,3,5-tri-4-pyridyl-1,2-ethenylbenzene and 3,5-difluorobenzoate. Single crystals of 1 under UV light irradiation exhibit rapid shrinking and bending, violent bursting-jumping, splitting, and cracking behavior. Single-crystal X-ray diffraction analysis and 1 H NMR spectroscopy reveal an unusual photoinduced phase transition involving a single-crystal-to-single-crystal [2+2] cycloaddition reaction that results in photomechanical responses. Interestingly, crystals of 1, which are triclinic with space group P 1 ‾ ${P\bar{1}}$ , are transformed into a higher symmetry, monoclinic cell with space group C2/c. This process represents a rare example of symmetry enhancement upon photoirradiation. The photomechanical activity is likely due to the sudden release of stress associated with strained molecular geometries and significant solid-state molecular movement arising from cleavage and formation of chemical bonds. A composite membrane fabricated from 1 and polyvinyl alcohol (PVA) also displays interesting photomechanical behavior under UV light illumination, indicating the material's potential as a photoactuator.

Realizing Vat-Photocycloaddition 3D Printing with Recyclable Synthetic Photorheological Silicone Fluids.

Synthetic silicone rubbers are finding a broad spectrum of applications, yet there is a demand for developing greener silicone rubbers with processability, recyclability, and reversible tunability in their mechanical properties. Here, a recyclable photorheological silicone fluid (RPSF) is developed, which realizes completely reversible wavelength-selective liquid-rubber conversion upon photoirradiation, relying on the reversible photocycloaddition of coumarin upon alternating irradiation of light with wavelengths of 365 (UV365 ) and 254 nm (UV254 ). Rheological studies demonstrate that the storage modulus of the developed RPSF increases by a factor of more than 100 000 upon UV365 irradiation to reach 20-50 kPa, while it decreases to ≈0.01 kPa upon UV254 irradiation. The reversibility of the photocycloaddition of coumarin enables the application of RPSF as a photodismantlable adhesive. Furthermore, unprecedented vat-photocycloaddition 3D printing of silicone rubber is realized by taking advantage of the excellent photocurability, that is, the dramatic increase in viscoelasticity upon UV365 irradiation.

Wavelength-Selective Photo-Cycloadditions of Styryl-Anthracene.

Light-tunable covalent chemistry is highly urgent in the fields of chemistry, biology, and materials science, especially for the smart materials and surface, due to the spatiotemporal control and feasible operation. Here, a new type of wavelength-selective photo-cycloaddition of styryl-anthracene carboxylic acid (SACA) is reported. Upon the irradiation of 450 nm visible light or 365 nm UV light, SACA can undergo [2+2] or [2+4] photocycloaddition, respectively. Furthermore, the [2+2] photocycloaddition induced by vis-light of 450 nm is reversible and can be disrupted by 365 nm UV light to form dimer-24 which cannot be photo-cleavable. Owing to the feasibility and spatiotemporal characteristics of UV-vis light-controlled photocycloaddition, the SACA possesses potential applications in various areas such as self-assembly, dynamic wrinkles, and fluorescence patterns, which are also explored and exhibited in this work.

Unravelling Supramolecular Photocycloaddition: Cavitand-Mediated Reactivity of 3-(Aryl)Acrylic Acids.

The supramolecular photocycloaddition (PCA) of 3-(phenyl)acrylic acid has been extensively pursued by chemists to study weak interactions and synthesize substituted cyclobutanes. The stereo- and regioselectivity of the products in a supramolecularly affected reaction are often used as a probe for assessing the nature of weak interactions and/or molecular ambience of the reactants. However, some crucial aspects of this chemistry have often remained underexplored in the past, especially within the context of interpreting strength and directionality of interactions based on reaction outcomes. We present a detailed study of the cavitand-mediated PCA of a new and suitable reactant (3-(naphthyl)acrylic acids) that exhibits labile photo-reversible chemistry, which is suitable for exploring previously un-explored aspects of the supramolecular PCA chemistry. Our studies afford important insights about this chemistry that should be considered while using product selectivity as a proxy for deducing intermolecular interactions.

Photocycloadditions for the Design of Reversible Photopolymerizations.

The quest for circular designs and ways to reuse polymer materials demands further advances in the development of reversible chemistries. Stimuli-responsive systems incorporated into polymer materials that enable the formation and cleavage of covalent bonds, hold great potential to reversibly decompose materials into their original building blocks. [2π+2π] photocycloadditions, for which the addition and reversion mechanism can be triggered by disparate wavelengths, stand as an attractive platform for triggering such controlled and reversible photoligation towards achieving renewable polymer materials. This perspective highlights the potential of this type of photochemistry to incorporate solid polymer materials and generate reversible polymerizations. The design of effective photoresponsive materials with specific functions requires the consideration of a number of parameters. Following a bottom-up approach - from molecular chemistry to macromolecular functionality - this perspective provides a recipe of the key aspects to consider in the design of such advanced renewable materials. Furthermore, examples of the state of the art in the field are highlighted and an overview of the fundamental challenges that remain is provided. Finally, an outlook on the next frontiers to cross is proposed.