Coumarin Dimer Research Articles

Synthesis of coumarin dimers by a microwave-assisted double multicomponent reaction

A synthesis of coumarin dimers highly functionalized was developed using a double enol-Ugi reaction. The use of microwave irradiation permits the construction of this complex coumarin derivatives in only 5 min.This is the first report of a double enol-Ugi condensation using dialdehydes and diamines affording peptidomimetic coumarin dimers with different linkers and substituents. This methodology permits to obtain molecular diversity and complexity by a multicomponent protocol under microwave activation. The described double enol-Ugi reactions demonstrate excellent atom economy and favourable waste prevention metrics.

Isolation and biological activities of chemical constituents from Aspergillus niger

Fungi, a renewable natural product resource trove, have garnered increasing attention recently. Aspergillus niger (A. niger) Ma001, a subspecies isolated from the human gut, exhibited moderate in vitro inhibition of carbapenem-resistant Acinetobacter baumannii (CRAB). However, research on its active ingredients remains insufficient. Therefore, chemical investigations of A. niger Ma001 resulted in the isolation and identification of 19 natural products. Among these, two were identified as new compounds: a coumarin dimer with an unusual 3,8' carbon bridge, designated as 7,7'-di-O-demethyl-3,8'-bisiderin (1), and a 3-hydroxyanthranilic acid derivative (9). Their structures were elucidated through comprehensive analyses utilizing mass spectroscopy and nuclear magnetic resonance. Bio-evaluations indicated that some of these compounds exhibited antibacterial, anti-inflammatory, or anticancer activities.

Coumarin Dimer Is an Effective Photomechanochemical AND Gate for Small-Molecule Release.

Stimulus-responsive gating of chemical reactions is of considerable practical and conceptual interest. For example, photocleavable protective groups and gating mechanophores allow the kinetics of purely thermally activated reactions to be controlled optically or by mechanical load by inducing the release of small-molecule reactants. Such release only in response to a sequential application of both stimuli (photomechanochemical gating) has not been demonstrated despite its unique expected benefits. Here, we describe computational and experimental evidence that coumarin dimers are highly promising moieties for realizing photomechanochemical control of small-molecule release. Such dimers are transparent and photochemically inert at wavelengths >300 nm but can be made to dissociate rapidly under tensile force. The resulting coumarins are mechanochemically and thermally stable, but rapidly release their payload upon irradiation. Our DFT calculations reveal that both strain-free and mechanochemical kinetics of dimer dissociation are highly tunable over an unusually broad range of rates by simple substitution. In head-to-head dimers, the phenyl groups act as molecular levers to allow systematic and predictable variation in the force sensitivity of the dissociation barriers by choice of the pulling axis. As a proof-of-concept, we synthesized and characterized the reactivity of one such dimer for photomechanochemically controlled release of aniline and its application for controlling bulk gelation.

Upgrading the Toolbox: Two‐Photon Absorption Induced Cleavage of Coumarin Dimers for Light‐Based 4D Printing

Upgrading the Toolbox: Two‐Photon Absorption Induced Cleavage of Coumarin Dimers for Light‐Based 4D Printing

Light‐controlled switchable underwater adhesive

AbstractDespite extensive efforts in designing and preparing switchable underwater adhesives, it is not easy to regulate the underwater adhesion strength locally and remotely. Here, we design and synthesize photoreversible copolymer of poly[dopamine methacrylamide‐co‐methoxyethyl‐acrylate‐co‐7‐(2‐methacryloyloxyethoxy)‐4‐methylcoumarin]. Due to the dynamic formation and breaking of chemical crosslinking networks within the smart adhesives, the material shows widely tunable adhesion strength from ∼150 to ∼450 kPa and long‐range reversible maneuverability under orthogonal 254 and 365 nm ultraviolet light stimulation via the coumarin dimerization and cycloreversion. Moreover, the adhesive exhibits good circulation performance and stability in an acid–base environment. It also demonstrated that the bolt can be coated with the smart adhesive material for on‐demand bonding. This design principle opens the door to the development of remotely controllable high‐performance smart underwater adhesives.

Upgrading the Toolbox: Two-Photon Absorption Induced Cleavage of Coumarin Dimers for Light-Based 4D Printing.

The use of light for shaping and changing matter is of high relevance in polymer and material science. Herein, a photopolymer method is presented, which comprises the combination of 3D photo-printing at 405nm light and subsequent modification under two-photon absorption (TPA) conditions at 532nm light, adding the fourth dimension. The TPA-triggered cycloreversion reaction of an intramolecular coumarin dimer (ICD) structure occurs within the absorbing material. The 3D-printable matrix does not show any degradation under the TPA conditions. With the presented photochemical tool of TPA processes inside absorbing 3D photo-printable matrices, new possibilities for post-printing modification, e. g. for smart materials, are added.

Programming Photodegradability into Vinylic Polymers via Radical Ring‐Opening Polymerization

AbstractIncorporation of photolabile moieties into the polymer backbone holds promise to remotely‐control polymer degradation. However, suitable synthetic avenues are limited, especially for radical polymerizations. Here we report a strategy to program photodegradability into vinylic polymers by exploiting the wavelength selectivity of photocycloadditions for radical ring‐opening polymerization (rROP). Irradiation of coumarin terminated allylic sulfides with UVA light initiated intramolecular [2+2] photocycloaddition producing cyclic macromonomers. Subsequent RAFT‐mediated rROP with methyl acrylate yielded copolymers that inherited the photoreactivity of the cyclic parent monomer. Irradiation with UVB initiated efficient photocycloreversion of the coumarin dimers, causing polymer degradation within minutes under UVB light or days under sunlight exposure. Our synthetic strategy may pave the way to insert photolabile linkages into vinylic polymers, tuning degradation for specific wavelengths.

Programming Photodegradability into Vinylic Polymers via Radical Ring-Opening Polymerization.

Incorporation of photolabile moieties into the polymer backbone holds promise to remotely-control polymer degradation. However, suitable synthetic avenues are limited, especially for radical polymerizations. Here we report a strategy to program photodegradability into vinylic polymers by exploiting the wavelength selectivity of photocycloadditions for radical ring-opening polymerization (rROP). Irradiation of coumarin terminated allylic sulfides with UVA light initiated intramolecular [2+2] photocycloaddition producing cyclic macromonomers. Subsequent RAFT-mediated rROP with methyl acrylate yielded copolymers that inherited the photoreactivity of the cyclic parent monomer. Irradiation with UVB initiated efficient photocycloreversion of the coumarin dimers, causing polymer degradation within minutes under UVB light or days under sunlight exposure. Our synthetic strategy may pave the way to insert photolabile linkages into vinylic polymers, tuning degradation for specific wavelengths.

Coumarin-functionalized metal-organic frameworks: adsorbents with photo-responsive active sites for adsorptive desulfurization.

Photo-responsive metal-organic frameworks (PMOFs) have great potential in on-demand controllable adsorption processes under distinct light conditions, which is challenging to realize by conventional adsorbents with static frameworks and properties. Here, we report a new type of adsorbent with photo-responsive active sites for adsorptive desulfurization. Coumarin monomers were incorporated in MIL-101(Cr) to construct the photo-responsive adsorbents by coordinating with unsaturated chromium sites. Trigged by UV light (>310 nm), coumarin monomers undergo dimerization to a cyclobutane structure, which forms a conjugation effect with π electrons on the aromatic ring of the sulfur compound, leading to remarkably increased uptake of 4,6-dimethyldibenzothiophene (4,6-DMDBT). Coumarin dimers can transform back to monomers under irradiation of 254 nm UV light, corresponding to decreased adsorption of 4,6-DMDBT. The change in adsorption amount between PMOF and the coumarin monomers and dimers is up to 62.8%. The present study might open up an avenue for the fabrication of adsorbents with on-demand active sites for various applications.

Photo-Crosslinked Coumarin-Containing Bis-Urea Amphiphile Hydrogels.

The design of photo-responsive supramolecular hydrogels based on coumarin dimerization and de-dimerization is described. The photo-responsive coumarin unit is chemically incorporated into an oligo(ethylene glycol) (OEG) bis-urea amphiphile that is capable of co-assembling with non-functionalized OEG amphiphile, to form supramolecular fibers. UV light with two different wavelengths (365 nm and 254 nm) is employed to induce a photo-reversible dimerization and de-dimerization process of coumarin units, respectively. The co-assembled solutions could be photo-crosslinked to induce a sol-to-gel transition through dimerization of coumarin with 365 nm UV light, and de-dimerization occurs with 254 nm UV light, to provide a weaker gel. In this system, the mechanical strength of supramolecular hydrogels can be tuned using the irradiation time, providing precise control of gelation in a supramolecular hydrogelator.

Intramolecular Coumarin-Dimer Containing Polyurethanes: Optical Tuning via Single- and Two-Photon Absorption Processes

The synthesis of an isomer-pure intramolecular coumarin dimer (ICD) in virtually unlimited amounts using a photo flow reactor is described. Based on this compound, polyurethanes with different ratios of hexamethylene diisocyanate and polytetrahydrofuran were synthesized and characterized. The reversibility of the photoinduced cycloaddition and cycloreversion reactions, one of the critical features, was compared for polymers prepared from closed ICDs and open ICDs. It was found that closed ICDs lead to a pre-orientation of the photoactive groups in the polymers, which results in a reduced loss in photoswitchable absorption. By varying the ICD content of the polymers, refractive indices ranging from 1.47 to 1.59 were achieved. With illumination, refractive index changes of Δn ≥ 0.02, as well as fluorescence changes, were achieved. Photoreactions induced by both single-photon absorption (SPA) and two-photon absorption (TPA) were studied. For the TPA-induced reaction, an autocatalytically sensitized mechanism was found. These novel polymers based on an intramolecular dimeric coumarin compound have great potential as optical materials with light-switchable properties, in particular, by TPA processes.

Nondestructive Photo-Cross-Linking of Microphase-Separated Diblock Polymers through Coumarin Dimerization

Nondestructive Photo-Cross-Linking of Microphase-Separated Diblock Polymers through Coumarin Dimerization

Morphology evolution of multi-responsive ABA triblock copolymers containing photo-crosslinkable coumarin molecules

Symmetric tri-block copolymer as P(DMAEMA-co-CuA)-b-PDMS-b-P(DMAEMA-co-CuA) was synthesized by atom transfer radical polymerization (ATRP) in which PDMS was used as bis-functionalized initiator. Moreover, PDMAEMA as multi-responsive hydrophilic segment was copolymerized with coumarin moieties as photocrosslinking agent. Variation of the ratio of hydrophilic/hydrophobic segments in block copolymers was resulted in different morphologies including snowman-like, hollow, spherical, and cubic structures where the morphology was affected by pH of media. The size of self-assembled tri-block copolymers was changed toward external stimuli including temperature, CO2 bubbling, and pH due to multi-responsivity of PDMAEMA block. The presence of photoactive coumarin molecules in hydrophilic PDMAEMA block was utilized for stabilizing the morphology in the self-assembled particles upon UV light irradiation (365 nm). Photocrosslinking of self-assembled particles by UV light-induced dimerization of coumarin molecules via [2π + 2π] cycloaddition reaction was investigated by spectroscopy and microscopy methods, and results indicated that morphology of the particles was stabilized after photocrosslinking. Also, the rate of coumarin dimerization was affected by its concentration, and size and morphology of the particles. According to the advantages of developed self-assembly system considering various UV-crosslinkable morphologies and multi-responsiveness, these structures have potential application in drug delivery systems for controlled release of doxorubicin (DOX).

Macroscalar Helices Co-Assembled from Chirality-Transferring Temperature-Responsive Carbohydrate-Based Bolaamphiphiles and 1,4-Benzenediboronic Acid.

We present the first example of macroscalar helices co‐assembled from temperature‐responsive carbohydrate‐based bolaamphiphiles (CHO‐Bolas) and 1,4‐benzenediboronic acid (BDBA). The CHO‐Bolas contained hydrophilic glucose or mannose moieties and a hydrophobic coumarin dimer. They showed temperature‐responsive reversible micelle‐to‐vesicle transition (MVT) in aqueous solutions. After the binding of carbohydrate moieties with boronic acids of BDBA in their alkaline solutions, right‐handed helices were formed via the temperature‐driven chirality transfer of d‐glucose or d‐mannose from the molecular to supramolecular level. These helices were co‐assembled by unreacted BDBA, boronate esters (B−O−C bonds) between CHO‐Bolas and BDBA, as well as boroxine anhydrides (B−O−B bonds) of self‐condensed BDBA. After heating at 300 °C under nitrogen, the helices displayed excellent morphological stability. Moreover, they emitted bright blue luminescence caused by strong self‐condensation of BDBA and decomposition of coumarin dimers.

Photocatalytic Oxidative [2+2] Cycloelimination Reactions with Flavinium Salts: Mechanistic Study and Influence of the Catalyst Structure.

Flavinium salts are frequently used in organocatalysis but their application in photoredox catalysis has not been systematically investigated to date. We synthesized a series of 5-ethyl-1,3-dimethylalloxazinium salts with different substituents in the positions 7 and 8 and investigated their application in light-dependent oxidative cycloelimination of cyclobutanes. Detailed mechanistic investigations with a coumarin dimer as a model substrate reveal that the reaction preferentially occurs via the triplet-born radical pair after electron transfer from the substrate to the triplet state of an alloxazinium salt. The very photostable 7,8-dimethoxy derivative is a superior catalyst with a sufficiently high oxidation power (E*=2.26 V) allowing the conversion of various cyclobutanes (with Eox up to 2.05 V) in high yields. Even compounds such as all-trans dimethyl 3,4-bis(4-methoxyphenyl)cyclobutane-1,2-dicarboxylate can be converted, whose opening requires a high activation energy due to a missing pre-activation caused by bulky adjacent substituents in cis-position.

Cycloreversion performance of coumarin and hetero-coumarin dimers under aerobic conditions: unexpected behavior triggered by UV-A light.

Photochemical [2+2]-cycloadditions of coumarin-like monomers are the textbook paradigms of photo-formation and photo-cleavage reactions. The electronic conjugation length of monomers and dimers is quite different which results in almost fully separated UV/Vis absorption bands in the UV-A and UV-C. This feature enables the selective light-controlled conversion between monomeric and dimeric forms by the choice of the appropriate wavelengths. Several applications are based on this kind of reversible photo linker without absorption in the visible range. But which is the best molecule from the coumarin family for such an application? Within this study, we compared the photochemical cleavage behavior of twelve coumarin-type cyclobutane dimers. In particular, the influence of isomer structure and substitution pattern was studied. Two dimers with an unexpected high quantum yield for cyclobutane cleavage were identified. This behavior is explained through the differing ring strain of the cyclobutane moiety. Electron donating substitutions of the framework, e.g. with a methoxy function (+M-effect), leads to a decreased oxidation potential, making the dimers sensitive towards oxidative dimer splitting. This result disqualifies coumarins, e.g. attached to a polymer backbone via an ether bond, often in the 7-position, because of their instabilities and side reactions in an aerobic environment. The methylated dimers (+I-effect) show excellent stability towards this undesired side reaction as well as a high cleavage efficiency upon irradiation with 265 nm. All twelve investigated dimers are ranked for their quantum efficiency and rate constant for cleavage at 265 nm, as well as their oxygen tolerance. As the most promising derivative within our scope for applications the methylated coumarin dimer was identified.

Molecular Damage Detection in an Elastomer Nanocomposite with a Coumarin Dimer Mechanophore.

Molecular force probes that generate optical responses to critical levels of mechanical stress (mechanochromophores) are increasingly attractive tools for identifying molecular sites that are most prone to failure. Here, a coumarin dimer mechanophore whose mechanical strength is comparable to that of the sulfur-sulfur bonds found in vulcanized rubbers is reported. It is further shown that the strain-induced scission of the coumarin dimer within the matrix of a particle-reinforced polybutadiene-based co-polymer can be detected and quantified by fluorescence spectroscopy, when cylinders of the nanocomposite are subjected to unconstrained uniaxial stress. The extent of the scission suggests that the coumarin dimers are molecular "weak links" within the matrix, and, by analogy, sulfur bridges are likely to be the same in vulcanized rubbers. The mechanophore is embedded in polymer main chains, grafting agent, and cross-linker positions in a polymer composite in order to generate experimental data to understand how macroscopic mechanical stress is transferred at the molecular scale especially in highly entangled cross-linked polymer nanocomposite. Finally, the extent of activation is enhanced by approximately an order of magnitude by changing the regiochemistry and stereochemistry of the coumarin dimer and embedding the mechanophore at the heterointerface of the particle-reinforced elastomer.

Synthesis of New Flexible Coumarin Dimers for Sodium and Potassium Differentiation.

Using fluorescence to detect biologically relevant metals has been studied extensively due to its rapid and low detection limit ability. Sodium and potassium differentiation is significant in diagnosis of many medical conditions. For this, we designed coumarin dimers as flexible fluorescent probes using ethylene glycol units for differentiation of sodium and potassium. To our best knowledge, use of these easy-to-synthesize coumarin dimers linked through ethylene glycol units are first in the literature. In fluorescence titration experiments, diethylene glycol linked coumarin-3-carboxylate dimer is responsive for sodium ions but not for potassium ions. The driving force for the complexation of metal cation and fluorescence probes is thought to be size-matching. To further explain the phenomenon, we synthesized coumarin dimer using 1,8- octanediol as the linker, and methyl ester of coumarin-3-carboxylic acid to investigate the effect of structural changes on the fluorescence intensity. These two compounds could not differentiate the sodium and potassium. Flexible coumarin dimers as fluorophores are shown to be useful for sensing sodium cation in the presence of potassium cation.

Migration of endothelial cells into photo-responsive hydrogels with tunable modulus under the presence of pro-inflammatory macrophages.

Cell migration in three-dimensional environment is extremely important for tissue regeneration and other biological processes. In this work, a model system was developed to study how endothelial cells (ECs) migrate into photo-responsive hydrogels under the presence of pro-inflammatory macrophages. The hydrogel was synthesized from hyaluronic acid grafted with coumarin and methacrylate moieties by both carbon–carbon covalent linking and coumarin dimerization under UV irradiation at 365 nm. The structure of the hydrogel was conveniently modulated by UV irradiation at 254 nm to decompose the coumarin dimers, leading to the significant decrease of modulus and increase of swelling ratio and mesh size. Under the presence of M1 macrophages, ECs were induced to migrate into the hydrogels with a different degree. A significant larger net displacement of ECs was found in the softer hydrogel obtained by irradiation with UV at 254 nm than in the stiffer original one at day 7.

Substituting Coumarins for Quinolinones: Altering the Cycloreversion Potential Energy Landscape.

The light-activated cleavage of cyclobutane-based systems via [2 + 2] cycloreversions, such as thymine and coumarin dimers, is an important but still poorly understood ultrafast photochemical reaction. Systems displaying reversible cycloreversion have found various uses in cross-linked polymers, enhancing gas adsorption affinities in inorganics, and light-activated medical therapies. We report the identification of a heterogeneous mode of cycloreversion for a rarely examined coumarin analogue system. Quinolinone monomers and dimers were probed using ultraviolet pumped, transient absorption spectroscopy and demonstrated radically different photophysical properties than coumarins. Monomers displayed enhanced intersystem crossing at almost 1:1 versus the combined nonradiative and radiative singlet decay, while the dimers underwent cycloreversion to a one excited-one ground state monomer photoproduct pair. The change in both systems was directly linked to the lactame group in the quinolinone motif. This discovery highlights the dramatic effects that small chemical changes can have on photoreaction pathways and opens up a new means to produce and develop more efficient cycloaddition-cycloreversion systems.