O-nitrobenzyl Group Research Articles

Nanocomplexes of Photolabile Polyelectrolyte and Upconversion Nanoparticles for Near-Infrared Light-Triggered Payload Release.

A new approach to encapsulating charged cargo molecules into a nanovector and subsequently using near-infrared (NIR) light to trigger the release is demonstrated. NIR light-responsive nanovector was prepared through electrostatic interaction-driven complexation between negatively charged silica-coated upconversion nanoparticles (UCNP@silica, 87 nm hydrodynamic diameter, polydispersity index ∼0.05) and a positively charged UV-labile polyelectrolyte bearing pendants of poly(ethylene glycol) and o-nitrobenzyl side groups; whereas charged fluorescein (FLU) was loaded through a co-complexation process. By controlling the amount of polyelectrolyte, UCNP@silica can be covered by the polymer, whereas remaining dispersed in aqueous solution. Under 980 nm laser excitation, UV light emitted by UCNP is absorbed by photolytic side groups within polyelectrolyte, which results in cleavage of o-nitrobenzyl groups and formation of carboxylic acid groups. Such NIR light-induced partial reversal of positive charge to negative charge on the polyelectrolyte layer disrupts the equilibrium among UCNP@silica, polyelectrolyte, and FLU and, consequently, leads to release of FLU molecules.

Family of BODIPY Photocages Cleaved by Single Photons of Visible/Near-Infrared Light.

Photocages are light-sensitive chemical protecting groups that provide external control over when, where, and how much of a biological substrate is activated in cells using targeted light irradiation. Regrettably, most popular photocages (e.g., o-nitrobenzyl groups) absorb cell-damaging ultraviolet wavelengths. A challenge with achieving longer wavelength bond-breaking photochemistry is that long-wavelength-absorbing chromophores have shorter excited-state lifetimes and diminished excited-state energies. However, here we report the synthesis of a family of BODIPY-derived photocages with tunable absorptions across the visible/near-infrared that release chemical cargo under irradiation. Derivatives with appended styryl groups feature absorptions above 700 nm, yielding photocages cleaved with the highest known wavelengths of light via a direct single-photon-release mechanism. Photorelease with red light is demonstrated in living HeLa cells, Drosophila S2 cells, and bovine GM07373 cells upon ∼5 min irradiation. No cytotoxicity is observed at 20 μM photocage concentration using the trypan blue exclusion assay. Improved B-alkylated derivatives feature improved quantum efficiencies of photorelease ∼20-fold larger, on par with the popular o-nitrobenzyl photocages (εΦ = 50-100 M-1 cm-1), but absorbing red/near-IR light in the biological window instead of UV light.

Using the 3-Diethylaminobenzyl Group as a Photocage in Aqueous Solution.

We have demonstrated that the 3-diethylaminobenzyl (DEABn) photolabile protecting group (PPG) is an effective and structurally simple PPG for releasing molecules in aqueous environment. In general, the photoreaction is clean, and the released substrate and the PPG product, i.e., 3-diethylaminobenzyl alcohol, are obtained in high yield. The clean photoreaction can also be achieved under mild ambient conditions with sunlight, while the reactant is stable under indoor lighting. Release of two substrates from one PPG chromophore in aqueous solution has been demonstrated to be feasible. We have also compared the uncaging properties of the DEABn and the widely used o-nitrobenzyl ( o-NB) group, given their comparable structural simplicity. With its clean and efficient photochemical reaction, DEABn should find wide applications, including in the basic and applied research areas where o-NB and its various derivatives are widely used.

Effects of Bulky End-Groups on the Crystallization Kinetics of Poly(ε-caprolactone) Homopolymers Confined in a Cylindrical Nanodomain

We examined the isothermal crystallization kinetics of poly(e-caprolactone) (PCL) homopolymers confined in a cylindrical nanodomain (nanocylinder) with 12.9 nm in diameter. The confined PCL homopolymers were prepared using the microphase separation of PCL-block-polystyrene (PCL-b-PS) diblock copolymers with a photocleavable o-nitrobenzyl group (ONB) at block junctions and the subsequent cleavage of ONB with UV light. Several PCL homopolymers with different end-groups, acetyl group (molecular weight MEG = 43 g/mol, original PCL homopolymer), adamantane (MEG = 163), cholesterol (MEG = 386), methyl 2,3,6-tri-o-benzoyl-α-d-galactopyranoside (MEG = 506), and vitrified PS (MEG = ∞, i.e., PCL blocks in PCL-b-PS), were prepared to gradually change their chain mobility in the nanocylinder. The crystallization rate of corresponding bulk PCL homopolymers (i.e., no spatial confinement imposed) decreased steadily with increasing MEG, suggesting that these end-groups had no extra effect on the crystallization but simpl...

NIR light and enzyme dual stimuli-responsive amphiphilic diblock copolymer assemblies

Using atom transfer radical polymerization (ATRP) and macromolecular azo coupling reaction, both o-nitrobenzyl (ONB) group and azobenzene group were efficiently incorporated into the center of the amphiphilic diblock copolymer chain. The prepared diblock copolymer was well characterized by UV–vis, 1H NMR, and GPC methods. Self-assembly of the amphiphilic copolymer in selected solvents can result in uniform self-assembly aggregates. In the presence of external stimuli [upconversion nanoparticles (UCNPs)/NIR light or enzyme], the amphiphilic diblock copolymer chain could be broken by the cleavage of ONB or azobenzene group, which would lead to the disruption of the self-assembly aggregates. This photo- and enzyme-triggered disruption process was proved by using transmission electron microscopy (TEM) and GPC method. Fluorescence emission spectra measurements indicated that the release of Nile red, a hydrophobic dye, encapsulated by the self-assembly aggregates, could be successfully realized under the NIR light and enzyme stimuli. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2450–2457

Light-Activated COS/H2S Donation from Photocaged Thiocarbamates.

Hydrogen sulfide (H2S) is an important biomolecule, and responsive chemical tools for its delivery are needed. Here, we utilize the photocleavable o-nitrobenzyl group to unmask caged thiocarbamates and to access photoactivated H2S releasing molecules. These donors function by the initial release of carbonyl sulfide (COS), which is quickly hydrolyzed to H2S by carbonic anhydrase (CA). Our investigations demonstrate that o-nitrobenzyl-caged thiocarbamates can serve as a donor platform for the bio-orthogonal stimulated release of COS/H2S.

Crystal orientation of poly(ε-caprolactone) chains confined in lamellar nanodomains: Effects of chain-ends tethering to nanodomain interfaces

We have examined the crystal orientation of poly (ε-caprolactone) (PCL) chains covalently tethered to nanodomain interfaces at both chain-ends (T2-PCL), one chain-end (T1-PCL), and no chain-end (PCL homopolymers, T0-PCL) all confined in an identical lamellar nanodomain (nanolamella). In order to prepare these PCL chains, we synthesized two kinds of lamella-forming polystyrene-block-PCL-block-polystyrene (PS-b-PCL-b-PS) triblock copolymers with photocleavable o-nitrobenzyl groups (ONB) at either or both of block junctions. The chain-ends tethering significantly affected the tilt angle φ between the c axis of PCL crystals and the normal of nanolamella interfaces (ND). That is, the c axis of T2-PCL crystals oriented almost perpendicular to ND (φ ≥ 70°), whereas that of T0-PCL crystals took completely parallel orientation against ND (φ ∼ 0°) at high crystallization temperatures (>32 °C). The T1-PCL crystal showed an intermediate orientation between T2-PCL and T0-PCL crystals (35° < φ < 55°), which depended moderately on the crystallization temperature. The difference in crystal orientation was discussed in terms of a delicate balance between the heterogeneous nucleation rate and subsequent crystal growth rate by considering the difference in chain mobility based on the state of chain-ends tethering.

Synthesis of Photo- and pH Dual-Sensitive Amphiphilic Copolymer PEG43-b-P(AA76-co-NBA35-co-tBA9) and Its Micellization as Leakage-Free Drug Delivery System for UV-Triggered Intracellular Delivery of Doxorubicin.

Novel photo- and pH dual-sensitive amphiphilic copolymers containing photolabile o-nitrobenzyl (NB) groups were designed via combination of ATRP, hydrolyzation, and simple esterification reaction and self-assembled into stimuli-regulated amphiphilic micelles in aqueous solution. On the basis of the optimization of the morphology and particle size of the micelles via modulating the number of the photocleavable o-nitrobenzyl acrylate (NBA) units, the unique ones assembled from PEG43-b-P(AA76-co-NBA35-co-tBA9) with an average hydrodynamic diameter (Dh) of 163 nm was selected as a potential drug delivery system (DDS) for UV-triggered delivery of doxorubicin (DOX). The micelles possessed a favorable drug-loading capacity (DLC) of 27.5%, with the hydrodynamic diameter of 213 nm after DOX-loading. Most importantly, the DOX-loaded PEG43-b-P(AA76-co-NBA35-co-tBA9) micelles exhibited a cumulative DOX release ratio of only 3.69% in the simulated physiological medium within 6 days without UV-irradiation, indicating their potential as leakage-free DDS. As in the acidic media mimicking the tumor microenvironment, a high cumulative DOX release ratio of 74.70% was achieved within 6 days after UV-irradiation for 20 min, showing a sustained release behavior. Under UV-irradiation, the photolabile o-nitrobenzyl moieties were cleaved off, the amphiphilic copolymer transformed into a water-soluble polymer, favoring the metabolism of drug carriers, and the micelles were demicellized to accelerate the drug release in a triggered or on-demand manner.

Synthesis of block copolymer with photo-decomposable polyurethane and its photo-initiated domino decomposition

A block copolymer consisting of a photo-decomposable polyurethane and poly(methyl methacrylate) (PMMA) was developed. The end-functionalized polyurethane (P2) was synthesized by polycondensation with the end-functionalization reagents. P2 possesses the photosensitive o-nitrobenzyl group and the 2-bromoisobutyryl group as the initiator of the atom transfer radical polymerization (ATRP). The block copolymer (P2-b-PMMA) was synthesized by the ATRP of methyl methacrylate (MMA) with P2 as the macroinitiator. The P2 block in P2-b-PMMA was decomposed by photo-irradiation at 365nm by the initiation of the photo-fries rearrangement of the urethane linkage and the subsequent domino reaction consistent with the elimination of the aza-quinone methide and decarboxylation. The photo-initiated decomposition of the P2 segment in the thin-film state was accomplished.

A dual-responsive nanocapsule via disulfide-induced self-assembly for therapeutic agent delivery.

One-step synthesis of fluorescent molecules (SNBDP) containing one disulfide bond and two o-nitrobenzyl groups was demonstrated via multi-component Passerini reaction. This hydrophobic SNBDP could self-assemble into nanocapsules (SNBDP NCs) in aqueous solution via disulfide-induced assembly. The obtained nanocapsules were stable in aqueous solution for several weeks and exhibited enhanced fluorescence when nanocapsules were destroyed due to disaggregation-induced emission. The nanocapsules not only were reduction-sensitive and light-responsive, but also could be endocytosed by HeLa cells for cellular imaging. The enhanced fluorescence in the glutathione (GSH) pretreated HeLa cells showed that the compound was reduction-sensitive in living cells. In vitro WST-8 assays showed the nanocapsules were biocompatible and could further be used as drug delivery carriers. Indocyanine green (ICG), a clinically approved NIR dye, was loaded into the nanocapsules (ICG@SNBDP NCs). ICG@SNBDP NCs showed enhanced photothermal efficacy compared with same concentration of free ICG under 808-nm laser irradiation. Consequently, ICG@SNBDP NCs upon NIR irradiation can effectively kill cancer cells through local hyperthermia. These results highlight the potential of disulfide-induced nanocapsules as smart nanoparticles for cellular imaging and therapeutic agent delivery.

Photodegradable self-assembling PAMAM dendrons for gene delivery involving dendriplex formation and phototriggered circular DNA release

Photoresponsive amphiphilic dendron bearing a photolabile o-nitrobenzyl group possesses self-assembly, DNA binding and photo-induced release.

Latent pH-responsive ratiometric fluorescent cluster based on self-assembled photoactivated SNARF derivatives

We have developed a self-assembled fluorescent cluster comprising a seminaphthorhodafluor (SNARF) derivative protected by a photoremovable o-nitrobenzyl group. Prior to UV irradiation, a colorless and nonfluorescent cluster was spontaneously assembled in aqueous solution. After UV irradiation, the self-assembled cluster remained intact and showed a large enhancement in pH-responsive fluorescence. The unique pH responsive fluorescent cluster could be used as a dual-emissive ratiometric fluorescent pH probe not only in the test tube but also in HeLa cell cultures.

Photocleavage of Poly(methyl acrylate) with Centrally Located o-Nitrobenzyl Moiety: Influence of Environment on Kinetics

We characterized the kinetics of a photocleavable o-nitrobenzyl (ONB)-modified poly(methyl acrylate) in solution and in film. Using atom transfer radical polymerization, a single photolabile ONB group was incorporated into the center of the polymer chain, resulting in a clearly defined photoresponse. The photocleavage behavior was characterized in three difference solvents and in film, and it was fit to an exponential model. The dependence of the reaction rate constants and quantum efficiency on the interaction parameter between the solvent and the polymer (χ12) and the molecular weight was investigated. Interestingly, as χ12 decreased, the reaction rate increased and the quantum efficiency increased.

Photo-Activatable Substrates for Site-Specific Differentiation of Stem Cells.

In this report, a UV sensitive, PEGylated PFSSTKTC (Pro-Phe-Ser-Ser-Thr-Lys-Thr-Cys) peptide was modified on quartz substrate to investigate the spatial controlled differentiation of stem cells. This substrate could restrict the cell adhesion due to the steric hindrance of PEG shell. With UV irradiation, PFSSTKTC became exposed owing to the breakage of o-nitrobenzyl group with the detachment of PEG shell. The irradiation boundary on substrate was stable in the long term. The in vitro osteogenic differentiation results revealed that under the site-specific irradiation, the mesenchymal stem cells (MSCs) could specifically differentiate into osteoblast under the induction of PFSSTKTC peptide. This photoactivatable biomaterial shows great potential for region controllable and precise MSCs differentiation.

Effects of Chain-Ends Tethering on the Crystallization Behavior of Poly(ε-caprolactone) Confined in Lamellar Nanodomains

We have investigated the effects of chain-ends tethering at nanodomain interfaces on the crystallization behavior of poly(e-caprolactone) (PCL) chains spatially confined in lamellar nanodomains. The PCL chains tethered at both chain-ends (T2-PCL), one chain-end (T1-PCL), and no chain-end (i.e., PCL homopolymers) (T0-PCL) were prepared from polystyrene-block-PCL-block-polystyrene (PS-b-PCL-b-PS) triblock copolymers having a photocleavable o-nitrobenzyl (ONB) group at either or both of block junctions. The lamellar nanodomain was provided by the microphase separation of PS-b-PCL-b-PS copolymers, in which T2-PCL was inherently confined. Subsequently, the ONB group was cleaved by the irradiation of ultraviolet light to yield T1-PCL or T0-PCL from T2-PCL without perturbing the lamellar nanodomain. T2-PCL showed an extremely low melting temperature and crystallinity as compared with T1-PCL and T0-PCL, indicating that the crystallization was significantly affected by chain mobility imposed by chain tethering at ...

Synthesis and characterization of methacrylate matrix resin bearing o-nitrobenzyl group

The matrix polymer PTBCHNB bearing o-nitrobenzyl group was successfully synthesized by copolymerization of tertiary-butyl methacrylate (TBMA), cyclohexyl methacrylate (CHMA) and o-nitrobenzyl methacrylate (NBMA) via reversible addition fragmentation chain transfer (RAFT) polymerization method. PTBCHNB was characterized by FTIR, 1HNMR, GPC and DSC. After UV irradiation, the o-nitrobenzyl groups of PTBCHNB were photocleaved and the resulting carboxyl groups were highly alkali soluble, and PTBCHNB was converted to PCHIBMA bearing carboxyl groups. So, the matrix polymer could be etched by mild alkali solution with no requirements of photoacid generators and other diverse additives. The photocleavable behaviors of PTBCHNB were determined by FTIR, 1H NMR and TGA analysis. The resist formulated with PTBCHNB and cast in THF solution showed square pattern of 10 μm×10 μm using a mercury-xenon lamp in a contact printing mode and tetramethyl-ammonium hydroxide aqueous solution as a developer.

Development of a photolabile protecting group for phosphodiesters in oligonucleotides.

A photolabile protecting group, consisting of an o-nitrobenzyl group and a 3-(2'-hydroxy-3',6'-dimethylphenyl)-2,2-dimethylpropyl moiety, was developed for phosphodiesters in oligodeoxyribonucleotides. Deprotection was triggered by photoirradiation and subsequent spontaneous cyclization to release the naked oligonucleotide.

Synthesis of nucleosides containing a photolabile 2-(2-nitrophenyl)propoxycarbonyl group

At present, DNA biochips are widely used in medicine as diagnostic systems [1, 2]. Oligonucleotide biochips are often obtained with the aid of photolabile protecting groups [3–7]. The latter should be stable under the conditions of oligonucleotide synthesis but should be readily removed by photolysis without involving the protected moiety. A widely used photolabile protecting group is the o-nitrobenzyl group [3, 8–10]. The goal of the present work was to extend the series of nucleosides protected by the photolabile 2-(2-nitrophenyl)propoxycarbonyl group and containing readily removable protecting groups in the aromatic heteroring, which can subsequently be used in the design of oligonucleotide biochips. We have synthesized previously unknown nucleosides 4–7. Compounds 4 and 5 were obtained by acylation of 2′-deoxyguanosine and 2′-deoxyadenosine with phenoxyacetyl chlorides 1 and 2, respectively. Nucleosides 6 and 7 protected by photolabile 2-(2-nitrophenyl)propoxycarbonyl groups were synthesized by treatment of compounds 4 and 5, respectively, with 2-(2-nitrophenyl)propyl chloroformate (3) which was prepared as described in [10]. Compounds 6 and 7 were isolated as mixtures of diastereoisomers. ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 1, pp. 141–144. © Pleiades Publishing, Ltd., 2015. Original Russian Text © E.B. Nikolaenkova, I.A. Os’kina, V.A. Savel’ev, A.Ya. Tikhonov, V.A. Ryabinin, A.N. Sinyakov, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 1, pp. 142–144.

Photoactivable heterocyclic cages in a comparative release study of butyric acid as a model drug

ng at the improvement of the photorelease of butyric acid – a model carboxylic acid drug, a set of heteroaromatic compounds based on acridine, naphtho[2,1-b]pyran, 3H-benzopyran fused julolidine and thioxo-naphtho[2,1-b]pyran were evaluated as benzyl-type phototriggers, in comparison with the well-known o-nitrobenzyl group. The corresponding ester cages were irradiated in a photochemical reactor at 254, 300, 350 and 419 nm, in two solvent systems (methanol or acetonitrile in 80:20 mixtures with HEPES buffer). Photolysis studies showed that, for some of the cages, the release of the active molecule occurred with short irradiation times using 419 nm. Time-resolved fluorescence was used to elucidate their photophysical properties and determine the decay kinetics. Studies were also carried out to assess the suitability of using two-photon excitation to address these compounds, which is advantageous if their use in biological systems is to be considered.

Multi-responsive polypeptidosome: characterization, morphology transformation, and triggered drug delivery.

The biodegradable polymeric nanomedicines that may be integrated with multi-stimuli-sensitivity to achieve triggered or on-demand drug release kinetics are challenging for polymer therapeutics and drug delivery systems. By controlling the structure transformation of one polypeptide-b-PEO copolymer, a novel multi-responsive polypeptide-based vesicle (polypeptidosome) presents the combined sensitivity of multiple physiological and clinic-related stimuli, and both morphology and size of the polypeptidosome are changed during the triggered process. The designer polypeptide has unique structures composed of 1) light-responsive o-nitrobenzyl groups, 2) oxidizable thioether linkers, 3) photo-caged redox thiol groups on parent poly(L-cysteine), and 4) tunable conformation, which enable the polypeptidosome to have a peculiar multi-response. The anticancer drug doxorubicin can be released in a controlled or on-off manner. The combination stimuli of UV irradiation and H2 O2 oxidation induces a large effect and a lower IC50 of 3.80 μg doxorubicin (DOX) equiv/mL compared to 5.28 μg DOX equiv/mL of individual H2 O2 trigger.