Hypochlorous acid (HClO) is produced by white blood cells to defend against injury and bacteria. However, as one of the reactive oxygen species, high intracellular HClO concentration could lead to chronic diseases that affect the cardiovascular and nervous systems. To monitor HClO concentrations in bio-samples, the fluorescent probe is preferred to have: a) absorbability in the far-red window with reduced light-toxicity and improved tissue penetration depth, b) ratiometric feature for accurate analysis. In this study, we reported a far-red ratiometric HClO fluorescence probe based on BODIPY chromophore and aldoxime sensing group. Not only the color change of the probe solution can be detected by naked eyes, but also the emission ratios (I/I) showed a significant increase upon the introduction of HClO. More importantly, the feasibility of HClO monitoring in bio-samples was demonstrated in vitro using a confocal microscope.

Light activation is an effective way to impart spatiotemporal control over oligonucleotide probes that are widely applied for gene expression regulation and target function investigation. Among the major oligonucleotide caging strategies, cyclization with a photocleavable linker is an elegant design, which affords both atom efficiency and stability in many biological environments. Here, we introduce an improved protocol for circular oligonucleotide synthesis requiring only one round of HPLC purification. With a series of poly-U oligonucleotide strands of different sizes and backbone modifications, the pre-photolysis caging stability and post-photolysis target binding affinity were studied through a denaturing gel assay and melting temperature measurements. A 14U 2'-OMe RNA probe was selected, with strong potential application in transcriptome analysis (TIVA) for mRNA isolation.

Creation of a flavylium polymethine dye set enabled selection of two fluorophores that match common lasers for exciting in the near-IR II region. Using these, researchers cast a broad net to catch any wavelength emission in the near-IR II region, and relied on selective to multiplex; this is a paradigm shift away from multiplexing via discrimination of wavelengths. Excitation multiplexing with flavylium dyes is a new and exciting strategy, but not yet a perfect one; it requires discrete water soluble fluorophores, including one that is turned on at 808 nm.

With the growing development of new contrast agents for optical imaging using near-infrared and shortwave infrared (SWIR) wavelengths, it is essential to have consistent bench-marks for emitters in these regions. Indocyanine green (ICG), a ubiquitous and FDA-approved organic dye and optical imaging agent, is commonly employed as a standard for photophysical properties and biological performance for imaging experiments at these wavelengths. Yet, its reported photophysical properties across organic and aqueous solvents vary greatly in the literature, which hinders its ability to be used as a consistent benchmark. Herein, we measure photophysical properties in organic and aqueous solvents using InGaAs detection (~950-1,700 nm), providing particular relevance for SWIR imaging.

Ifenprodil is an important negative allosteric modulator of the N-methyl-D-aspartate (NMDA) receptors. We have synthesized caged and photoswitchable derivatives of this small molecule drug. Caged ifenprodil was biologically inert before photolysis, UV irradiation efficiently released the drug allowing selective inhibition of GluN2B-containing NMDA receptors. Azobenzene-modified ifenprodil, on the other hand, is inert in both its and configurations, although modeling predicted the s form to be able to bind to the receptor. The disparity in effectiveness between the two compounds reflects, in part, the inherent ability of each method in manipulating the binding properties of drugs. With appropriate structure-activity relationship uncaging enables binary control of effector binding, whereas photoswitching using feely diffusable chromophores shifts the dose-response curve of drug-receptor interaction. Our data suggest that the efficacy of pharmacophores having a confined binding site such as ifenprodil can be controlled more easily by uncaging in comparison to photoswitching.

TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally-related Ru(II)-imidozo[4,5-f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter- or quaterthiophene changes the nature of the long-lived triplet state from metal-to-ligand charge-transfer to ππ* character. The addition of the third thiophene thus presents a critical juncture which not only determines the photophysics of the complex but most importantly its capacity for O generation and hence the potential of the complex to be used as a photocytotoxic agent.

Acid-sensing ion channels (ASICs), present in both central and peripheral neurons, respond to changes in extracellular protons. They play important roles in many symptoms and diseases, such as pain, ischemic stroke and neurodegenerative diseases. Herein, we report a novel approach to activate ASICs with the precision of light using organic photoacid generators (PAGs), which are molecules that release H upon light illumination, and have been recently used in biomedical studies. The PAGs showed low toxicity in dark conditions. Under LED light illumination, ASICs activation and consequent calcium ion influx was monitored and analysed by fluorescence microscopy, and showed a strong light-dependent response. This approach allows the activation of ASICs with the precision of light, and may be valuable to help better elucidate the molecular mechanism of ASICs and unveil their roles in physiology, pathophysiology, and behaviour.

We report that an NMR spectrometer equipped with a high-power LED light source can be used to study a fast enantioselective photocatalytic [2+2] cycloaddition. While traditional applications of NMR provide considerable information on reaction mechanisms, they are often ineffective for observing fast reactions. Recently, motivated by renewed interest in organic photochemistry, several approaches have been reported for monitoring of photochemical reactions. These previously disclosed methods, however, have rarely been applied to rapid (<5 min) photochemical reactions. Furthermore, these approaches have not previously been used to interrogate the mechanisms of photocatalytic energy-transfer reactions. In the present work, we describe our experimental setup and demonstrate its utility by determining a phenomenological rate law for a model photocatalytic energy-transfer cycloaddition reaction.

Previous time-resolved spectroscopic experiments and static quantum-chemical calculations attributed nitronaphthalene derivatives one of the fastest time scales for intersystem crossing within organic molecules, reaching the 100 fs mark. Nonadiabatic dynamics simulations on three nitronaphthalene derivatives challenge this view, showing that the experimentally observed ∼100 fs process corresponds to internal conversion in the singlet manifolds. Intersystem crossing, instead, takes place on a longer time scale of ∼1 ps. The dynamics simulations further reveal that the spin transitions occur via two distinct pathways with different contribution for the three systems, which are determined by electronic factors and the torsion of the nitro group. This study, therefore, indicates that the existence of sub-picosecond intersystem crossing in other nitroaromatic molecules should be questioned.

Photo-controlled affinity reagents seek to provide modular spatiotemporal control of bioactivity by conferring photo-switchability of function on an affinity reagent scaffold. Here we used Rosetta-based computational methods to screen for sites on the Fynomer affinity reagent structure for attachment of photoswitchable cross-linkers. Both established UV-based cross-linkers (azobenzene-iodoacetamide (IAC)) and an azonium-based efficient red light switchable cross-linker, piperazino-tetra--methoxy azobenzene (PIP), were then tested experimentally. Several sites compatible with Fynomer function were identified, including sites showing rapid (<10s) red light (633 nm) modulation of function. While a range of overall target binding affinities were observed, the degree of photo-switchability of Fynomer function was generally small (<2-fold). Computational models suggest that local flexibility limits the degree of switching seen in these designs.

Cyclobutene lactones hold great potential as synthetic building blocks, yet their preparation by photochemical rearrangement in batch can often be a bottleneck in synthetic studies. We report the use of flow photochemistry as a tool to enable a higher-throughput approach to the synthesis of 2-oxabicyclo[2.2.0]hex-5-en-3-one, which reduces reaction times from 24 h to 10 min. Accordingly, a significantly improved throughput of 144 mg/h (vs 14-21 mg/h in batch) was achieved. Scale-out experiments showed problematic reactor fouling and steps were taken to explore and minimize this effect.

Adsorption of organic molecules at ZnO nanoparticle surfaces enables the transfer of energy or charge across resulting organic-inorganic interfaces and, consequently, determines the optoelectronic performance of ZnO based hybrids. We investigated on aqueous colloidal ZnO dispersions adsorption-induced changes with photoluminescence (PL) and electron paramagnetic resonance (EPR) spectroscopy. Citrate and acetate ion adsorption increases or decreases radiative exciton annihilation at hν = 3.3 eV and at room temperature, respectively. Searching for a correspondence between PL emission and the yield of trapped charge carriers originating from exciton separation - using photon energies of hν = 4.6 eV and fluxes of = 10 cm s for excitation - we found that there is a negligible fraction of paramagnetic products that originate from exciton separation. Upon polychromatic excitation with significantly higher photon fluxes (Ṅ = 10 cm·s), ZnO specific shallow defects trap unpaired electrons in citrate and acetate functionalized samples. The adsorption dependent PL intensity changes and the excitation parameter dependent yield of separated charges (EPR) in colloidal ZnO nanoparticles underline that the distribution over the different exciton annihilation channels sensitively depends on interface composition and the intensity of the photoexcitation light.

The use of a modified prototype continuous flow reactor (CFR) as a pivotal part of a number of versatile singlet oxygen-mediated reaction sequences is presented herein. These sequences target rapid access to structural complexity and diversity. The prototype reactor achieves high conversions and productivities by attaining large specific surface areas for these biphasic reactions. In the reactor, the reaction solution is nebulized (using either oxygen or air) and the resulting aerosol is irradiated by an LED jacket that surrounds the Pyrex reaction chamber. The one pot procedures developed herein are, according to many different criteria, both highly efficient and green. The key common intermediates and the source of both the complexity and variety of the final products are -acyl imminium ions (NAI; protonated -acyl enamines). The initial substrates are simple and readily accessible furans and the diverse array of products is composed of different complex γ-lactams. Many of the products are of particular interest due to their close relationships to known biologically active molecules.

Tanaka et al. (., , , 1718) recently reported the three-dimensional (3D) structure of the oxygen evolving complex (OEC) of photosystem II (PSII) by X-ray diffraction (XRD) using extremely low X-ray doses of 0.03 and 0.12 MGy. They observed two different 3D structures of the CaMnO cluster with different hydrogen-bonding interactions in the S state of OEC keeping the surrounding polypeptide frameworks of PSII the same. Our Jahn-Teller (JT) deformation formula based on large-scale quantum mechanics/molecular mechanics (QM/MM) was applied for these low-dose XRD structures, elucidating important roles of JT effects of the Mn ion for subtle geometric distortions of the CaMnO cluster in OEC of PSII. The JT deformation formula revealed the similarity between the low-dose XRD and damage-free serial femtosecond X-ray diffraction (SFX) structures of the CaMnO cluster in the dark stable state. The extremely low-dose XRD structures were not damaged by X-ray irradiation. Implications of the present results are discussed in relation to recent SFX results and a blue print for the design of artificial photocatalysts for water oxidation.

A novel acid-responsive single trichromatic luminescent dye capable of emitting pure white light (WL) is reported. A newly designed -phenylene-bridged bipyrrole bearing -alkylimino groups () specifically provides WL emission upon mixing with trifluoroacetic acid (TFA) in a CHCl solution. The emission originates from the trichromatic luminescent behavior of upon protonation of the imino groups. The blue-light-emitting exhibits dramatic color changes in fluorescence to orange and green upon mono- and diprotonation, respectively, providing a wide emission band in the range of =400-800 nm that provide WL when the compound is in a dynamic equilibrium between the three states. The sample also exhibits low self-absorption of the emitted light and a high fluorescence quantum yield upon excitation with UV light.

Exposure to low-intensity radiation in the near-infrared (NIR) spectral region matching the optically transparent "phototherapeutic window" of biological tissues can be applied to directly populate spin-restricted excited states of light-responsive compounds. This unconventional and unprecedented approach is introduced herein as a new strategy to overcome some of the major unresolved problems observed in the rapidly emerging fields of photopharmacology and molecular photomedicine, where practical applications in living cells and organisms are still limited by undesired side reactions and insufficient light penetration. Water-soluble and biocompatible metal complexes with a significant degree of spin-orbit coupling were identified as target candidates for testing our new hypothesis. As a first example, a dark-stable manganese carbonyl complex acting as a visible-light-triggered CO-releasing molecule (Photo-CORM) is shown to be photoactivated by NIR radiation, although apparently no spectroscopically evident absorption bands are detectable in this low-energy region. This quite remarkable effect is ascribed to a strongly restricted, but obviously not completely forbidden optical population of the lowest triplet excited state manifold of the diamagnetic complex from the singlet ground state.

Vitamin A based bisretinoid accumulation is a major focus in the study of macular degeneration. Whether specific endogenous lysosomal proteins can bind A2E, a pronounced bisretinoid in lipofuscin granules in retinal pigment epithelial cells, and interfere with enzymatic or photoinduced oxidation of such, has not been explored. Herein, using fluorescence and electronic absorption spectroscopy and mass spectrometry, we demonstrate that Saposin B, a critical protein in the degradation of sulfatides and "flushing" of lipids, can bind A2E, preventing its HO-dependent enzymatic oxidation by horseradish peroxidase and photooxidation by blue light (=450-460 nm).

Long-distance biological electron transfer occurs through a hopping mechanism and often involves tyrosine as a high potential intermediate, for example in the early charge separation steps during photosynthesis. Protein design allows for the development of minimal systems to study the underlying principles of complex systems. Herein, we report the development of the first ruthenium-linked designed protein for the photogeneration of a tyrosine radical by intramolecular electron transfer.