O-nitrobenzyl Ester Research Articles

A facile design of smart silica nanocarriers via surface-initiated RAFT polymerization as a dual-stimuli drug release platform

The rational design of hybrid nanostructures with an active core and a modified shell can promote several biological applications. Herein, a coating platform has been developed to obtain monodispersed core-shell magnetic mesoporous silica nanocarriers. The surface of silica shells has been successfully modified by disulfide bonds and the photoresponsive polymer, poly(2-nitrobenzyl acrylate) (PNBA), via RAFT polymerization using azobisisobutyronitrile (AIBN) as a thermal initiator. The results showed that these nanocarriers have nanospherical morphologies with high porosity, large surface areas, and suitable pore volumes. Furthermore, ibuprofen (IBU) as a model drug has been loaded easily into the polymeric nanocontainers with a high loading content, followed by coating with β-Cyclodextrin (β-CD) as effective gatekeeper molecules. Treating these nanocarriers with ultraviolet light causes the photocleavage of o-nitrobenzyl ester moieties contained in the growing polymer chains. The controlled release of the loaded IBU cargo can be achieved by ultraviolet light, or reduction cleavable of the disulfide bond, or both together. Interestingly, the magnetic core can enhance the release process through magnetic guiding and pushing the nanocarriers to the targeted sites by using an external magnet or a directed magnetic field. The prepared photodegradable polymer nanocarriers can be widely applied in the fields of controlled drug delivery systems (DDS) and pharmacologically active polymers.

Photopatternable Epoxy-Based Thermosets.

The present work provides a comparative study on the photopatterning of epoxy-based thermosets as a function of network structure and network mobility. Local switching of solubility properties by light of a defined wavelength is achieved by exploiting versatile o-nitrobenzyl ester (o-NBE) chemistry. o-NBE derivatives with terminal epoxy groups are synthetized and thermally cured with different types of cycloaliphatic anhydrides via nucleophilic ring opening reaction. By varying the structure of the anhydride, glass transition temperature (Tg) and surface hardness are adjusted over a broad range. Once the network has been formed, the photolysis of the o-NBE groups enables a well-defined degradation of the 3D network. Fourier transform infrared (FT-IR) spectroscopy studies demonstrate that cleavage rate and cleavage yield increase with rising mobility of the network, which is either facilitated by inherent network properties (Tg below room temperature) or a simultaneous heating of the thermosets above their Tg. The formation of soluble species is evidenced by sol-gel analysis, revealing that low-Tg networks are prone to secondary photoreactions at higher exposure doses, which lead to a re-crosslinking of the cleaved polymer chains. The change in solubility properties is exploited to inscribe positive tone micropatterns within the thermosets by photolithographic techniques. Contrast curves show that the resist performance of rigid networks is superior to flexible ones, with a contrast of 1.17 and a resolution of 8 µm.

New chirally modified bisphosphonates for synthesis of individual beta,gamma-CHX-deoxynucleotide diastereomers

Individual diastereomers of CXY bisphosphonate analogues of dNTPs or NTPs are useful chemical stereoprobes to investigate interactions within the chiral active site environment of enzymes such as polymerases and kinases. We previously reported synthetic access to β,γ-CHX-dGTPs (X = F or Cl) via a bisphosphonate synthon with an (R)-methyl mandelate auxiliary and have extended this approach to dTTP and dATP analogues. As removal of the chiral auxiliary by (Pd/C) hydrogenolysis is incompatible with the cytosine heterocycle and also with X = Br, we have now designed bisphosphonate synthons using (R)-(+)-α-ethylbenzylamine or methyl (R)-(–)-phenylglycine auxiliaries and equipped with an o-nitrobenzyl ester protecting group allowing photochemical deprotection. These new synthons have made possible the first syntheses of individual dCTP and monobromo-substituted dNTP β,γ-CHX diastereomers.

Alignment of Lyotropic Liquid Crystalline Conjugated Polymers in Floating Films.

Directed alignment of polymer chains plays an indispensable role in charge transport properties. We focus not only on a specific method to induce the alignment but also on the design of a liquid crystalline (LC) conjugated polymer to take advantage of an intrinsic self-assembly characteristic. We synthesized a lyotropic LC conjugated polymer, CP1-P, having o-nitrobenzyl (ONB) esters as photocleavable side chains and adopted a floating film transfer method to induce the polymer chain alignment through a lyotropic LC phase transition. An optimum amount of a high boiling point solvent (1,2-dichlorobenzene) in chloroform turned out to be an important factor to maximize the polymer chain alignment. The hole transport mobility along the polymer chain alignment direction was 13–14 times higher than that in the direction perpendicular to the alignment. In addition, the removal of side chains resulted in the solvent resistivity while maintaining the alignment feature in organic thin-film transistors.

One-pot one-step synthesis of a photo-cleavable cross-linker via Passerini reaction for fabrication of responsive polymeric particles

A new approach for the synthesis of a photo-cleavable cross-linker and preparation of light-responsive polymeric particles is proposed in the current work. A multicomponent reaction, Passerini reaction, is employed as a one-pot one-step synthetic approach for the preparation of the acrylate-based cross-linker (hexane-1,6-diylbis(azanediyl))bis(1-(2-nitrophenyl)-2-oxoethane-2,1-diyl) diacrylate) (PCDA). Briefly, Passerini reaction of 1,6-diisocyanohexane, 2-nitrobenzaldehyde and acrylic acid yields the photo-cleavable diacrylate with o-nitrobenzyl ester moieties. Subsequently, the cross-linker is successfully utilized in the preparation of poly(methyl methacrylate) microspheres and nanospheres via suspension and miniemulsion polymerization, respectively. Finally, light-induced degradations of the polymeric particles are conducted under UV light illumination (around 366 nm). All compounds and products in each step are well characterized by FTIR, 1H-NMR, UV–Vis spectroscopy, light microscopy and SEM.

Light-controllable viscoelastic properties of a photolabile carboxybetaine ester-based polymer with mucus and cellulose sulfate

In this study, the interaction of a photoswitchable carboxybetaine ester-based polymer with mucus and cellulose sulfate was elucidated, showing light-controllable viscoelastic properties. This polymer contains photolabile o-nitrobenzyl ester moieties, allowing transformation from its polycationic form to a charge-balanced nontoxic polyzwitterionic form upon photolysis by irradiation at 365 nm. Rheological studies revealed that the polycationic form of the polymer interacts with mucus and cellulose sulfate to create a physically crosslinked hydrogel based primarily on polyionic complexation and partially on hydrogen bonding. In these cases, a dramatic change in the rheological synergism was confirmed for mucus-based and cellulose sulfate-based systems. Rheological synergism with the polycationic carboxybetaine ester sample reached nearly 4 and 3.8, while it decreased with the charge-balanced zwitterionic sample to 0.3 and 0.7 after irradiation of the mucus-based and cellulose sulfate-based systems, respectively. Disruption of the interaction during light-induced transformation was on-line monitored and showed a 3 and 3.3 times decrease in the elastic modulus for the mucus-based and cellulose sulfate-based systems, respectively. These properties suggest possible biomedical applications, such as spatially controlled drug release or laparoscopic utilization.

Photoresponsive Nanovehicle for Two Independent Wavelength Light-Triggered Sequential Release of P-gp shRNA and Doxorubicin To Optimize and Enhance Synergistic Therapy of Multidrug-Resistant Cancer.

Prerelease of RNA molecules than chemotherapeutic drugs with a sufficient interval is a vital prerequisite for RNA/drug co-delivery strategy to overcome multidrug resistance (MDR) of cancer cells, but how to precisely control their release at different time points is still a grand challenge up to now. This study aims to on-demand remotely manipulate RNA and drug release in real time through single delivery system to sequentially play their respective roles for optimizing and enhancing their synergistic antitumor effects. To this end, a photoresponsive mesoporous silica nanoparticle (PMSN) is fabricated as a co-delivery vehicle of P-glycoprotein (P-gp) short-hairpin RNA (shRNA) and photocaged prodrug of doxorubicin (DOX), by which the orthogonal and sequential release of shRNA and DOX can be achieved using an external light. In our design, the cationic poly[2-( N, N-dimethylaminoethyl)methacrylate] is introduced onto the PMSN surface through a light-sensitive coumarin ester derivative linker to adsorb P-gp shRNA, whereas the photocleavable o-nitrobenzyl ester derivative-caged DOX is loaded into the inner pores of the PMSN. The PMSN is found to be effectively internalized by MDR cancer cells, and the release of the shRNA and DOX is demonstrated to be independently regulated by 405 and 365 nm light irradiations due to selectively cleaved coumarin and o-nitrobenzyl ester, resulting in enhanced drug retention, and finally bring out optimized and significantly improved chemotherapeutic effects both in vitro and in vivo for MDR cancer treatment, which might hold extensive application prospects in MDR cancer treatment in future.

Recent Advances in Cyclodextrin-Based Light-Responsive Supramolecular Systems.

Cyclodextrins (CDs), one of the host molecules in supramolecular chemistry, can host guest molecules to form inclusion complexes via non-covalent and reversible host-guest interactions. CD-based light-responsive supramolecular systems are typically constructed using CDs and guest molecules with light-responsive moieties, including azobenzene, arylazopyrazole, o-nitrobenzyl ester, pyrenylmethyl ester, coumarin, and anthracene. To date, numerous efforts have been reported on the topic of CD-based light-responsive supramolecular systems, but these have not yet been highlighted in a separated review. This review summarizes the efforts reported over the past ten years. The main text of this review is divided into five sections (vesicles, micelles, gels, capturers, and nanovalves) according to the formation of self-assemblies. This feature article aims to afford a comprehensive understanding of the light-responsive moieties used in the construction of CD-based light-responsive supramolecular systems and to provide a helpful guide for the further design of CD-based light-responsive supramolecular systems.

Stimuli-responsive thiol-epoxy networks with photo-switchable bulk and surface properties.

In the present work, the versatile nature of o-nitrobenzyl chemistry is used to alter bulk and surface properties of thiol-epoxy networks. By introducing an irreversibly photocleavable chromophore into the click network, material properties such as wettability, solubility and crosslink density are switched locally by light of a defined wavelength. The synthesis of photo-responsive thiol-epoxy networks follows a photobase-catalyzed nucleophilic ring opening of epoxy monomers with photolabile o-nitrobenzyl ester (o-NBE) groups across multi-functional thiols. To ensure temporal control of the curing reaction, a photolatent base is employed releasing a strong amidine-type base upon light exposure, which acts as an efficient catalyst for the thiol epoxy addition reaction. The spectral sensitivity of the photolatent base is extended to the visible light region by adding a selected photosensitizer to the resin formulation. Thus, in the case of photoactivation of the crosslinking reaction the photorelease of the base does not interfere with the absorbance of the o-NBE groups. Once the network has been formed, the susceptibility of the o-NBE groups towards photocleavage reactions is used for a well-defined network degradation upon UV exposure. Sol–gel analysis evidences the formation of soluble species, which is exploited to inscribe positive tone micropatterns by photolithography. Along with the localized tuning of network structure, the irreversible photoreaction is exploited to change the surface wettability of thiol-epoxy networks. The contact angle of water significantly decreases upon UV exposure due to the photo-induced formation of hydrophilic cleavage products enabling the inscription of domains with different surface wettability by photolithography.

Reduction/photo dual-responsive polymeric prodrug nanoparticles for programmed siRNA and doxorubicin delivery.

Dual and multi-stimuli responsive polymeric nanoparticles that respond to two or more signals can further improve drug release performance compared with nanoparticles that respond to a single stimulus. However, usage of such nanoparticles to deliver siRNA and chemotherapeutic drugs in a sequential manner are currently very rare; meanwhile, this technology is vital to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. By loading o-nitrobenzyl ester derivative caged DOX (DOC) into the inner poly(lactic-co-glycolic acid) (PLGA) core and adsorbing siRNA of P-gp protein onto the cationic polymeric shell derived from a disulfide-containing alkyl modified polyethylenimine (C16-S-S-PEI), here, a reduction/photo dual responsive device (RPDRD) is successfully designed for programmed P-gp siRNA and doxorubicin delivery. The dual-stimuli design of the RPDRD allows tumor microenvironment-specific and rapid release of P-gp siRNA triggered by the enrichment of reducing agent glutathione (GSH, up to 10 mM) for reversal of drug resistance by initially suppressing P-gp protein expression in MCF/ADR cells and then selectively triggering drug release by external light for chemotherapy afterwards. The sequential release behavior of P-gp siRNA and DOX can be demonstrated both in vitro and in vivo, thus enhancing the intracellular drug retention and optimizing the chemotherapy efficacy of DOX by silencing P-gp; this strategy may have extensive application prospects in MDR cancer treatment in future.

One-pot strategy for preparation of photo- and chemo-cleavable polystyrene containing o-nitrobenzyl ester moieties

A new strategy have been developed for preparation of photo- and chemo-cleavable polystyrene by incorporating o-nitrobenzyl ester moiety as a photosensitive linking unit into the main chain of the polymer. The strategy is based on the highly efficient esterification reaction of dicarboxylic acid, 4,4′-azobis(4-cyanovaleric acid), with organic dihalide, 2-nitro-1,3-phenylene bis(methylene-2-chloroacetate) and free radical polymerization of styrene. Multiblock polystyrenes were successfully synthesized by a combination of the esterification reaction and the radical polymerization of styrene by one-pot approach. Moreover, the photocleavage behavior of the multiblock PS in THF solution and in solid state was examined under UV irradiation at room temperature in air atmosphere. The results demonstrated that the multiblock polystyrenes could be cleaved into separate PS blocks not only by UV light, but also by hydrolysis of the ester groups. In addition, the incorporation of o-nitrobenzyl units into the backbone of PS has no obvious influence on the thermal stability.

Light triggered formation of photo-responsive epoxy based networks

Taking advantage of versatile o-nitrobenzyl chemistry, the present study highlights the design of photocurable epoxy networks that undergo spatially controlled bond cleavage in response to UV irradiation. The synthetic strategy involves the preparation of epoxy monomers with photolabile o-nitrobenzyl ester (o-NBE) links that are cured via photoinduced cationic ring opening reaction. Two different photoinitiation systems are employed which do not interfere with the absorbance of the o-NBE groups. The first initiation mechanism exploits the direct photolysis of N-hydroxynaphthalimide triflate upon deep UV exposure and the second mechanism follows a free radical promoted cationic polymerization upon visible light illumination. The crosslinking and cleavage kinetics of the photodegradable epoxy networks are characterized by spectroscopic techniques. In thin films, the UV induced increase in solubility is confirmed by sol-gel analysis and used for the fabrication of positive tone photoresists. Patterned films are obtained by photolithographic processes and microscopic analyses reveal that the resists provide a resolution of 4 μm and a good contrast behavior.

Photocleavage of Covalently Immobilized Amphiphilic Block Copolymer: From Bilayer to Monolayer

We developed and verified a method to create a photocleavable smart surface. Using the grafting to approach, we covalently attached an intelligently designed tailor-made diblock copolymer to a silicon wafer. The photocleavable moiety, o-nitrobenzyl (ONB) ester, was integrated into the copolymer at the junction point between the hydrophilic poly(ethylene oxide) (PEO) and the hydrophobic polystyrene (PS) chains. The well-defined azide bearing amphiphilic block copolymer was synthesized via a general stepwise strategy that combines atom transfer radical polymerization (ATRP) and copper(I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC), ending with azidation. The azide end-functionalized copolymer chains were covalently bound to the alkyne-immobilized silicon wafer by CuAAC. The smart surface was exposed to UV irradiation, resulting in photocleavage of the grafted ONB linker. As a result of the photocleavage and subsequent removal of the o-nitrosobenzaldehyde bearing PEO, the PS layer remained on the surface. To confirm the behavior, film thickness and wettability changes were investigated before and after UV irradiation using AFM and contact angle measurements. Integration of photocleavable polymers through covalent grafting to solid surfaces contributes responsiveness to such materials that can find a wide array of applications in advanced devices.

Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery.

In this study, pH, reduction and light triple-responsive nanocarriers based on hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated atom transfer radical polymerization. Both reduction-cleavable disulfide bond and light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and final nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers with a high loading capacity, and quickly released in response to the stimuli of reducing agent, acid environment or UV light irradiation. In addition, flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies indicated that the nanocarriers were efficiently internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into the cytoplasm under external UV light irradiation, (ii) better cytotoxicity against HeLa cells, and (iii) superior control over drug delivery and release. Thus, the triple-responsive nanocarriers present highly promising potentials as a drug delivery platform for cancer therapy.

Photocleavable epoxy based materials

The present study aims at the development of photodegradable epoxy based materials comprising o-nitrobenzyl ester links that undergo well defined bond cleavage in response to UV irradiation. New bi-functional epoxy based monomers bearing o-nitrobenzyl ester groups are synthesized and thermally cured with an anhydride hardener to yield photosensitive polymers and duromers. The UV induced changes in solubility are exploited for the preparation of positive-type photoresists. Thin patterned films are obtained by photolithographic processes and characterized by microscopic techniques. The results evidence that sensitive resist materials with good resolution and high contrast behavior can be accomplished. Along with resist technology, the applicability of o-nitrobenzyl chemistry in the design of recyclable polymer materials with thicknesses in the millimeter range is evaluated. By monitoring the thermo-mechanical properties upon UV illumination, a distinctive depletion of storage modulus and glass transition temperature is observed with increasing exposure dose. Additionally, single fiber pull-out tests are carried out revealing a significant decrease of the interfacial adhesion at the fiber-matrix interface due to the phototriggered cleavage reaction.

A facile approach to catechol containing UV dismantlable adhesives

We report a facile synthetic approach to a new type of catechol containing UV dimantlable adhesive. A series of linear polymers containing pendent catechol moieties and main chain o-nitrobenzyl ester groups were synthesized by the Passerini multicomponent polymerization (MCP) of a di-o-nitrobenzaldehyde, 1,6-diisocyanohexane, 3-(3,4-dihydroxyphenyl) propionic acid, and undecanoic acid. The content of the catechol moieties was adjusted by varying the molar ratio of 3-(3,4-dihydroxyphenyl) propionic acid to undecanoic acid. The thermal properties of these polymers were investigated, they are stable up to 250 °C, and the glass transition temperatures (Tg) are in the range of 17–70 °C. Increasing the catechol content will increase the Tg and slightly decrease the thermal stability. The pendent catechol groups and the in situ formed o-nitrobenzyl ester linkages in the polymer main chain endow the polymer with dual functions, substrate adhesiveness and UV degradation. The UV degradation process was monitored by 1H NMR, GPC, UV–Vis and FTIR. Lap shear strength tests revealed that the adhesion performance of these polymers could be tuned by varying the catechol contents. UV irradiation could cleave the polymer chains, thus decreasing the adhesion strength.

Photocleavage of the Corona Chains of Rigid-Rod Block Copolymer Micelles

A polyferrocenyldimethylsilane-block-poly(2-vinylpyridine) sample with a photocleavable o-nitrobenzyl ester (ONB) group at the junction (PFS35-hv-P2VP400) was synthesized by copper-catalyzed coupling of a P2VP-ONB-alkyne with a PFS-azide. Rodlike core-crystalline micelles of uniform length and uniform width were prepared in 2-propanol, a selective solvent for P2VP. Samples of these micelles were photoirradiated with UV-A light (peak emission 360 nm), which induced cleavage at the core–corona junction. Prolonged irradiation (24 h) led to aggregation and precipitation of the corona-cleaved micelles. One could see by TEM that the width of the micelles in the aggregates was significantly reduced (from 49 to 21 nm) because of the loss of the P2VP block, while the PFS core length (L) remained unchanged. For one micelle sample with Lw = 320 nm (650 polymer molecules per micelle), the time course of the irradiation was monitored by GPC, TEM, and multiangle light scattering. After 1 h irradiation, 60% of the coron...

Thiophene-Based Conjugated Polymers with Photolabile Solubilizing Side Chains

This paper describes a series of thiophene-based conjugated polymers that become insoluble upon irradiation with ultraviolet light. Stille or Suzuki reactions of appropriately substituted 2,5-bromothiophene derivatives yielded terthiophene and polythiophene derivatives with either o-nitrobenzyl (ONB) ester or ONB ether photolabile side chains with n-octyl substituents. Light-induced cleavage of these ONB side chains with ultraviolet light at 365 nm cleaves the octyl chains responsible for solubilization of the polymers away from the conjugated main chains, rendering them insoluble. Consistent with the accepted mechanism of ONB photolysis, those structural modifications that would yield a more stable benzylic radical—methyl substitution on the benzylic position, replacement of the ester with an ether, or both—yielded more efficient photolyses as determined by (i) quantum yields of photolysis of ONB-substituted terthiophenes, and (ii) the percentage of polymer that persists in UV-irradiated thin films upon ...

Synthesis, self-assembly, and degradation of amphiphilic triblock copolymers with fully photodegradable hydrophobic blocks

The development of stimuli-responsive materials is of significant interest for many applications including drug delivery, medical imaging, sensors, and microfluidic devices. Among the available stimuli, light is particularly attractive as it can be applied with high spatial and temporal resolution. We describe here the synthesis of amphiphilic triblock copolymers composed of poly(ethylene glycol) and a hydrophobic block containing o-nitrobenzyl esters throughout the backbone using copper-catalyzed azide–alkyne cycloaddition chemistry. These materials were designed to have a high weight fraction of the hydrophobic block to favour nonmicellar aggregates. The self-assembly in water was studied using nanoprecipitation and the resulting assemblies were characterized by dynamic light scattering and transmission electron microscopy. Under optimized conditions, it was possible to prepare polymer vesicles, commonly referred to as polymersomes, with diameters of approximately 100 nm. The degradation of these materials in response to UV light was studied by spectroscopy, light scattering, and electron microscopy, demonstrating that the vesicles were broken down. These results suggest the potential of these materials for applications such as encapsulation and release.

Facile One-step Micropatterning Using Photodegradable Methacrylated Gelatin Hydrogels for Improved Cardiomyocyte Organization and Alignment.

Hydrogels are often employed as temporary platforms for cell proliferation and tissue organization in vitro. Researchers have incorporated photodegradable moieties into synthetic polymeric hydrogels as a means of achieving spatiotemporal control over material properties. In this study protein-based photodegradable hydrogels composed of methacrylated gelatin (GelMA) and a crosslinker containing o-nitrobenzyl ester groups have been developed. The hydrogels are able to degrade rapidly and specifically in response to UV light and can be photopatterned to a variety of shapes and dimensions in a one-step process. Micropatterned photodegradable hydrogels are shown to improve cell distribution, alignment and beating regularity of cultured neonatal rat cardiomyocytes. Overall this work introduces a new class of photodegradable hydrogel based on natural and biofunctional polymers as cell culture substrates for improving cellular organization and function.