Light‐sensitive Intelligent Drug Delivery Systems†

Drug delivery systems (DDS) capable of releasing an active molecule at the appropriate site and at a rate that adjusts in response to the progression of the disease or to certain functions/biorhythms of the organism are particularly appealing. Biocompatible materials sensitive to certain physiological variables or external physicochemical stimuli (intelligent materials) can be used for achieving this aim. Light‐responsiveness is receiving increasing attention owing to the possibility of developing materials sensitive to innocuous electromagnetic radiation (mainly in the UV, visible and near‐infrared range), which can be applied on demand at well delimited sites of the body. Some light‐responsive DDS are of a single use (i.e. the light triggers an irreversible structural change that provokes the delivery of the entire dose) while others able to undergo reversible structural changes when cycles of light/dark are applied, behave as multi‐switchable carriers (releasing the drug in a pulsatile manner). In this review, the mechanisms used to develop polymeric micelles, gels, liposomes and nanocomposites with light‐sensitiveness are analyzed. Examples of the capability of some polymeric, lipidic and inorganic structures to regulate the release of small solutes and biomacromolecules are presented and the potential of light‐sensitive carriers as functional components of intelligent DDS is discussed.     

Engineering a Chemical Switch into the Light‐driven Proton Pump Proteorhodopsin by Cysteine Mutagenesis and Thiol Modification

For applications in synthetic biology, for example, the bottom‐up assembly of biomolecular nanofactories, modules of specific and controllable functionalities are essential. Of fundamental importance in such systems are energizing modules, which are able to establish an electrochemical gradient across a vesicular membrane as an energy source for powering other modules. Light‐driven proton pumps like proteorhodopsin (PR) are excellent candidates for efficient energy conversion. We have extended the versatility of PR by implementing an on/off switch based on reversible chemical modification of a site‐specifically introduced cysteine residue. The position of this cysteine residue in PR was identified by structure‐based cysteine mutagenesis combined with a proton‐pumping assay using E. coli cells overexpressing PR and PR proteoliposomes. The identified PR mutant represents the first light‐driven proton pump that can be chemically switched on/off depending on the requirements of the molecular system.     

Light‐driven and aggregation‐induced emission from side‐chain azoindazole polymers

The well‐defined azoindazole‐containing homopolymer, poly(6‐{6‐[(4‐dimethylamino) phenylazo]‐indazole}‐hexyl methacrylate) (PDHMA), and amphiphilic diblock copolymer, poly({6‐[6‐(4‐dimethylamino)phenylazo]‐indazole}‐hexyl methacrylate)‐b‐poly(2‐(dimethylamino)ethylmethacrylate) (PDHMA_m‐b‐PDMAEMA_n), were successfully prepared via reversible addition‐fragmentation chain transfer polymerization technique. The homopolymer and amphiphilic diblock copolymer in CH₂Cl₂ exhibited intense fluorescence emission accompanied by trans–cis photoisomerization of azoindazole group under UV irradiation. The experiment results indicated that the intense fluorescence emission may be attributed to an inhibition of photoinduced electron transfer of the cis form of azoindazole. On the other hand, the intense fluorescence emission of amphiphilic diblock copolymers in water‐tetrahydrofuran mixture was observed, which increased with the volume ratio of water in the mixed solvent. The self‐aggregation behaviors of three amphiphilic diblock copolymers were examined by transmission electron microscopy, laser light scattering, and UV–vis spectra. The restriction of intramolecular rotation of the azoindazole groups in aggregates was considered as the main cause of aggregation‐induced fluorescence emission. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.     

All‐Trans Retinal Mediates Light‐Induced Oxidation in Single Living Rod Photoreceptors†

All‐trans retinal is a potent photosensitizer that is released in photoreceptor outer segments by the photoactivated visual pigment following the detection of light. Photoreceptor outer segments also contain high concentrations of polyunsaturated fatty acids, and are thus particularly susceptible to oxidative damage such as that initiated by light via a photosensitizer. Upon its release, all‐trans retinal is reduced within the outer segment to all‐trans retinol, through a reaction requiring metabolic input in the form of NADPH. The phototoxic potential of physiologically generated all‐trans retinal was examined in single living rod photoreceptors obtained from frog (Rana pipiens) retinas. Light‐induced oxidation was measured with fluorescence imaging using an oxidation‐sensitive indicator dye from the shift in fluorescence between the intact and oxidized forms. Light‐induced oxidation was highest in metabolically compromised rod outer segments following photoactivation of the visual pigment rhodopsin, and after a time interval, sufficiently long to ensure the release of all‐trans retinal. Furthermore, light‐induced oxidation increased with the concentration of exogenously added all‐trans retinal. The results show that the all‐trans retinal generated during the detection of light can mediate light‐induced oxidation. Its removal through reduction to all‐trans retinol protects photoreceptor outer segments against light‐induced oxidative damage.     

Light‐induced Modulation of Protein Dynamics During the Photocycle of Bacteriorhodopsin†

Knowledge about the dynamical properties of a protein is of essential importance for understanding the structure–dynamics–function relationship at the atomic level. So far, however, the correlation between internal protein dynamics and functionality has only been studied indirectly in steady‐state experiments by variation of external parameters like temperature and hydration. In the present study we describe a novel type of (laser‐neutron) pump‐probe experiment, which combines in situ optical activation of the biological function of a membrane protein with a time‐dependent monitoring of the protein dynamics using quasielastic neutron scattering. As a first successful application we present data obtained selectively in the ground state and in the M‐intermediate of bacteriorhodopsin (BR). Temporary alterations in both localized reorientational protein motions and harmonic vibrational dynamics have been observed during the photocycle of BR. This observation is a direct proof for the functional significance of protein structural flexibility, which is correlated with the large‐scale structural changes in the protein structure occurring during the M‐intermediate. We anticipate that functionally important modulations of protein dynamics as observed here are of relevance for most other proteins exhibiting conformational transitions in the time course of functional operation.     

Initial Electrode Kinetics of Anion Intercalation and De‐intercalation in Nonaqueous Al‐Graphite Batteries†

Graphitic materials with intercalated sites are considered as the mostly used positive electrode materials in nonaqueous Al batteries. Unlike the small‐size cations, the intercalation/de‐intercalation of large‐size anions into/out of graphite would induce large volume expansion and micro‐structure reconfiguration, leading to unexpected coulombic efficiency in the full cells (<95% within initial several cycles). For understanding the irreversible processes induced by anion intercalation/de‐intercalation (AlCl₄^–), here the kinetics of first two cycles for the Al‐graphite batteries have been systematically studied. To study kinetics behaviors at representative states, a combined method upon galvanostatic intermittent titration technique and electrochemical impedance spectroscopy has been carried out. The achieved diffusion coefficients of the positive electrodes assembled with different graphite sizes suggest that size effect also plays a critical role in determining the electrochemical kinetics in the mass transport in both electrolyte and graphitic layers as well as in interface reaction. The morphologies and micro‐structures of the post‐cycled graphite electrodes have been also experimentally studied, which also well supports the irreversible intercalation/de‐intercalation behaviors in graphite electrodes. The results offer a significant platform to well understand the essential factors in tailoring coulombic efficiency from a kinetic view, which would be helpful in promoting the graphite electrodes in Al batteries.     

Light‐driven atom transfer radical polymerization on supramolecular complexes of conjugated polymers and single‐walled carbon nanotubes

Previous approaches used to decorate latently reactive conjugated polymer‐coated carbon nanotube complexes have utilized “grafting‐to” strategies. Here, we coat the carbon nanotube surface with a conjugated polymer whose side chains contain the radical initiator, α‐bromoisobutyrate, which enables atom transfer radical polymerization (ATRP) from the polymer–nanotube surface. Using light to generate Cu(I) in situ, ATRP is used to grow narrow dispersity polymer chains from the polymer–nanotube surface. We confirm the successful polymerization of (meth)acrylates from the polymer–nanotube surface using a combination of gel permeation chromatography and infrared spectroscopy. Strikingly, we demonstrate that nanotube optoelectronic properties are preserved after radical‐mediated polymer grafting using Raman spectroscopy and photoluminescence mapping. Overall, this work elucidates a method to grow narrow dispersity polymer chains from the polymer–nanotube surface using light‐driven radical chemistry, with concurrent preservation of nanotube optoelectronic properties. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2015–2020     

Individual‐Molecule Perspective Analysis of Chemical Reaction Networks: The Case of a Light‐Driven Supramolecular Pump

The first study in which stochastic simulations of a two‐component molecular machine are performed in the mass‐action regime is presented. This system is an autonomous molecular pump consisting of a photoactive axle that creates a directed flow of rings through it by exploiting light energy away from equilibrium. The investigation demonstrates that the pump can operate in two regimes, both experimentally accessible, in which light‐driven steps can be rate‐determining or not. The number of photons exploited by an individual molecular pump, as well as the precision of cycling and the overall efficiency, critically rely on the operating regime of the machine. This approach provides useful information not only to guide the chemical design of a self‐assembling molecular device with desired features, but also to elucidate the effect of the environment on its performance, thus facilitating its experimental investigation.     

Preparation of Silver Carbonate and its Application as Visible Light‐driven Photocatalyst Without Sacrificial Reagent

Visible light‐driven photocatalyst is the current research focus and silver oxyacid salts with p‐block elements are the promising candidates. In this research, Ag₂CO₃ was prepared by a facile precipitation method and used to degrade the pollutants from waters. The results revealed that the silver carbonate with monoclinic structure quickly decomposed methyl orange and rhodamine B in less than 15 min under visible light irradiation. When it was recycled six times, the degradation of methyl orange still can reach 87% after 30 min. The calculated band gap of Ag₂CO₃ was 2.312 eV with Valence band edge potential of 2.685 eV and Conduction band 0.373 eV vs NHE, which endowed the excellent photo‐oxidation ability of silver carbonate. Photogenerated holes and ozone anion radicals were the primary active species in the photo‐oxidization degradation of dye. The generation of metallic silver resulted from photocorrosion and the consequent reduction in the ozone anion radical amount led to the performance degradation of Ag₂CO₃. The simple preparation method and high photocatalytic performance of Ag₂CO₃ increases its prospect of application in future.     

Light‐Induced Retinal Degeneration Is Prevented by Zinc,a Component in the Age‐related Eye Disease Study Formulation†

Mineral supplements are often included in multivitamin preparations because of their beneficial effects on metabolism. In this study, we used an animal model of light‐induced retinal degeneration to test for photoreceptor cell protection by the essential trace element zinc. Rats were treated with various doses of zinc oxide and then exposed to intense visible light for as long as 8 h. Zinc treatment effectively prevented retinal light damage as determined by rhodopsin and retinal DNA recovery, histology and electrophoretic analysis of DNA damage and oxidized retinal proteins. Zinc oxide was particularly effective when given before light exposure and at doses two‐ to four‐fold higher than recommended by the age‐related eye disease study group. Treated rats exhibited higher serum and retinal pigment epithelial zinc levels and an altered retinal gene expression profile. Using an Ingenuity database, 512 genes with known functional annotations were found to be responsive to zinc supplementation, with 45% of these falling into a network related to cellular growth, proliferation, cell cycle and death. Although these data suggest an integrated and extensive regulatory response, zinc induced changes in gene expression also appear to enhance antioxidative capacity in retina and reduce oxidative damage arising from intense light exposure.     

Visible‐Light‐Promoted Polycyclizations of Dienynes

A variety of linear dienynes can deliver complex tetracyclic frameworks in the presence of an Ir^III complex and visible light. Product formation involves the generation of four new C?C bonds and six contiguous stereocenters, which decorate two [3.1.0] bicyclic units tethered through their bridging quaternary carbon atoms. The internal alkyne acts as a formal dicarbenoid for the generation of two cyclopropanes in these radical cation cascades. This behavior has not been previously observed for organic reactive intermediates and can be extended to intermolecular reactions and diendiynes.     

Functional and Photochemical Characterization of a Light‐Driven Proton Pump from the Gammaproteobacterium Pantoea vagans

Photoactive retinal proteins are widely distributed throughout the domains of the microbial world (i.e., bacteria, archaea, and eukarya). Here we describe three retinal proteins belonging to a phylogenetic clade with a unique DTG motif. Light‐induced decrease in the environmental pH and its inhibition by carbonyl cyanide m‐chlorophenylhydrazone revealed that these retinal proteins function as light‐driven outward electrogenic proton pumps. We further characterized one of these proteins, Pantoea vagans rhodopsin (PvR), spectroscopically. Visible spectroscopy and high‐performance liquid chromatography revealed that PvR has an absorption maximum at 538 nm with the retinal chromophore predominantly in the all‐trans form (>90%) under both dark and light conditions. We estimated the pK_a values of the protonated Schiff base of the retinal chromophore and its counterion as approximately 13.5 and 2.1, respectively, by using pH titration experiments, and the photochemical reaction cycle of PvR was measured by time‐resolved flash‐photolysis in the millisecond timeframe. We observed a blue‐shifted and a red‐shifted intermediate, which we assigned as M‐like and O‐like intermediates, respectively. Decay of the M‐like intermediate was highly sensitive to environmental pH, suggesting that proton uptake is coupled to decay of the M‐like intermediate. From these results, we propose a putative model for the photoreaction of PvR.     

Visible‐Light‐Driven Janus Microvehicles in Biological Media

A light‐driven multifunctional Janus micromotor for the removal of bacterial endotoxins and heavy metals is described. The micromotor was assembled by using the biocompatible polymer polycaprolactone for the encapsulation of CdTe or CdSe@ZnS quantum dots (QDs) as photoactive materials and an asymmetric Fe₃O₄ patch for propulsion. The micromotors can be activated with visible light (470–490 nm) to propel in peroxide or glucose media by a diffusiophoretic mechanism. Efficient propulsion was observed for the first time in complex samples such as human blood serum. These properties were exploited for efficient endotoxin removal using lipopolysaccharides from Escherichia coli O111:B4 as a model toxin. The micromotors were also used for mercury removal by cationic exchange with the CdSe@ZnS core–shell QDs. Cytotoxicity assays in HeLa cell lines demonstrated the high biocompatibility of the micromotors for future detoxification applications.     

Light‐Driven Self‐Healing of Nanoparticle‐Based Metamolecules

Metamolecules and crystals consisting of nanoscale building blocks offer rich models to study colloidal chemistry, materials science, and photonics. Herein we demonstrate the self‐assembly of colloidal Ag nanoparticles into quasi‐one‐dimensional metamolecules with an intriguing self‐healing ability in a linearly polarized optical field. By investigating the spatial stability of the metamolecules, we found that the origin of self‐healing is the inhomogeneous interparticle electrodynamic interactions enhanced by the formation of unusual nanoparticle dimers, which minimize the free energy of the whole structure. The equilibrium configuration and self‐healing behavior can be further tuned by modifying the electrical double layers surrounding the nanoparticles. Our results reveal a unique route to build self‐healing colloidal structures assembled from simple metal nanoparticles. This approach could potentially lead to reconfigurable plasmonic devices for photonic and sensing applications.     

Insights into Light‐driven DNA Repair by Photolyases: Challenges and Opportunities for Electronic Structure Theory

Ultraviolet radiation causes two of the most abundant mutagenic and cytotoxic DNA lesions: cyclobutane pyrimidine dimers and 6‐4 photoproducts. (6‐4) Photolyases are light‐activated enzymes that selectively bind to DNA and trigger repair of mutagenic 6‐4 photoproducts via photoinduced electron transfer from flavin adenine dinucleotide anion (FADH^?) to the lesion triggering repair. This review provides an overview of the sequential steps of the repair process, that is light absorption and resonance energy transfer, photoinduced electron transfer and electron‐induced splitting mechanisms, with an emphasis on the role of theory and computation. In addition, theoretical calculations and physical properties that can be used to classify specific mechanism are discussed in an effort to trace the fundamental aspects of each individual step and assist the interpretation of experimental data. The current challenges and suggested future directions are outlined for each step, concluding with a view on the future.     

Visible‐Light‐Assisted Gold‐Catalyzed Fluoroarylation of Allenoates

A strategically novel synthetic method for the fluoroarylation of allenic ester was developed that enables the expedient construction of a host of β‐fluoroalkyl‐containing cinnamate derivatives. The reaction proceeds through visible‐light‐promoted gold redox catalysis, occurs smoothly under very mild reaction conditions, accommodates a large variety of functional groups, and more importantly allows the incorporation of fluorine and aryl groups with excellent regio‐ and stereoselectivity. The concomitant activation mode for both the allene motif and the hydrogen fluoride is key for the success of the reaction.