Synthesis of 1H-isoindolin-1-ones via a simple photodecarboxylative addition of carboxylates to phthalimides and evaluation of their antibiotic activity.

A variety of 3-hydroxy-isoindolin-1-one derivatives were synthesized using the photodecarboxylative addition of carboxylates to phthalimide derivatives in aqueous media. Subsequent acid-catalyzed dehydration furnished 3-(alkyl and aryl)methyleneisoindolin-1-ones with variable E-diastereoselectivity in good to excellent overall yields. Noteworthy, the parent 3-phenylmethyleneisoindolin-1-one underwent isomerization and oxidative decomposition when exposed to light and air. Selected 3-hydroxy-isoindolin-1-one and 3-(alkyl and aryl)methyleneisoindolin-1-one derivatives showed moderate antibacterial activity that justifies future elaboration and study of these important bioactive scaffolds.

Synthesis and Investigation of Flavanone Derivatives as Potential New Anti-Inflammatory Agents.

Flavonoids are polyphenols with broad known pharmacological properties. A series of 2,3-dihydroflavanone derivatives were thus synthesized and investigated for their anti-inflammatory activities. The target flavanones were prepared through cyclization of 2'-hydroxychalcone derivatives, the later obtained by Claisen-Schmidt condensation. Since nitric oxide (NO) represents an important inflammatory mediator, the effects of various flavanones on the NO production in the LPS-induced RAW 264.7 macrophage were assessed in vitro using the Griess test. The most active compounds were flavanone (4G), 2'-carboxy-5,7-dimethoxy-flavanone (4F), 4'-bromo-5,7-dimethoxy-flavanone (4D), and 2'-carboxyflavanone (4J), with IC50 values of 0.603, 0.906, 1.030, and 1.830 µg/mL, respectively. In comparison, pinocembrin achieved an IC50 value of 203.60 µg/mL. Thus, the derivatives synthesized in this work had a higher NO inhibition capacity compared to pinocembrin, demonstrating the importance of pharmacomodulation to improve the biological potential of natural molecules. SARs suggested that the use of a carboxyl-group in the meta-position of the B-ring increases biological activity, whereas compounds carrying halogen substituents in the para-position were less active. The addition of methoxy-groups in the meta-position of the A-ring somewhat decreased the activity. This study successfully identified new bioactive flavanones as promising candidates for the development of new anti-inflammatory agents.

Solar Photooxygenations for the Manufacturing of Fine Chemicals-Technologies and Applications.

Photooxygenation reactions involving singlet oxygen (1O2) are utilized industrially as a mild and sustainable access to oxygenated products. Due to the usage of organic dyes as photosensitizers, these transformations can be successfully conducted using natural sunlight. Modern solar chemical reactors enable outdoor operations on the demonstration (multigram) to technical (multikilogram) scales and have subsequently been employed for the manufacturing of fine chemicals such as fragrances or biologically active compounds. This review will highlight examples of solar photooxygenations for the manufacturing of industrially relevant target compounds and will discuss current challenges and opportunities of this sustainable methodology.

Continuous Flow Photochemical and Thermal Multi-Step Synthesis of Bioactive 3-Arylmethylene-2,3-Dihydro-1H-Isoindolin-1-Ones.

An effective multi-step continuous flow approach towards N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones, including the local anesthetic compound AL-12, has been realized. Compared to the traditional decoupled batch processes, the combined photochemical-thermal-thermal flow setup rapidly provides the desired target compounds in superior yields and significantly shorter reaction times.

Solar Photochemical Synthesis: From the Beginnings of Organic Photochemistry to the Solar Manufacturing of Commodity Chemicals.

Natural sunlight offers a cost-efficient and sustainable energy source for photochemical reactions. In contrast to the lengthy and small-scale "flask in the sun" procedures of the past, modern solar concentrator systems nowadays significantly shorten reaction times and enable technical-scale operations. After a brief historical introduction, this review presents the most important solar reactor types and their successful application in preparative solar syntheses. The examples demonstrate that solar manufacturing of fine chemicals is technically feasible and environmentally sustainable. After over 100 years, Ciamician's prophetic vision of "the photochemistry of the future" as a clean and green manufacturing methodology has yet to be realized. At the same time, his warning "for nature is not in a hurry but mankind is" is still valid today. It is hoped that this review will lead to a renewed interest in this truly enlightening technology, that it will stimulate photochemists and photochemical engineers to "go back to the roots onto the roofs" and that it will ultimately result in industrial applications in the foreseeable future.

Advanced oxidation process-mediated removal of pharmaceuticals from water: A review.

Pharmaceuticals, which are frequently detected in natural and wastewater bodies as well as drinking water have attracted considerable attention, because they do not readily biodegrade and may persist and remain toxic. As a result, pharmaceutical residues pose on-going and potential health and environmental risks. To tackle these emerging contaminants, advanced oxidation processes (AOPs) such as photo-Fenton, sonolysis, electrochemical oxidation, radiation and ozonation etc. have been applied to remove pharmaceuticals. These processes utilize the high reactivity of hydroxyl radicals to progressively oxidize organic compounds to innocuous products. This review provides an overview of the findings from recent studies, which have applied AOPs to degrade pharmaceutical compounds. Included is a discussion that links various factors of TiO2-mediated photocatalytic treatment to its effectiveness in degrading pharmaceutical residues. This review furthermore highlights the success of AOPs in the removal of pharmaceuticals from different water matrices and recommendations for future studies are outlined.

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones.

The synthesis of various 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones was realized following a simple three-step process. The protocol utilized the photodecarboxylative addition of readily available carboxylates to N-(bromoalkyl)phthalimides as a versatile and efficient key step. The initially obtained hydroxyphthalimidines were readily converted to the desired N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms.

Studies in organic and physical photochemistry - an interdisciplinary approach.

Traditionally, organic photochemistry when applied to synthesis strongly interacts with physical chemistry. The aim of this review is to illustrate this very fruitful interdisciplinary approach and cooperation. A profound understanding of the photochemical reactivity and reaction mechanisms is particularly helpful for optimization and application of these reactions. Some typical reactions and particular aspects are reported such as the Norrish-Type II reaction and the Yang cyclization and related transformations, the [2 + 2] photocycloadditions, particularly the Paternò-Büchi reaction, photochemical electron transfer induced transformations, different kinds of catalytic reactions such as photoredox catalysis for organic synthesis and photooxygenation are discussed. Particular aspects such as the structure and reactivity of aryl cations, photochemical reactions in the crystalline state, chiral memory, different mechanisms of hydrogen transfer in photochemical reactions or fundamental aspects of stereoselectivity are discussed. Photochemical reactions are also investigated in the context of chemical engineering. Particularly, continuous flow reactors are of interest. Novel reactor systems are developed and modeling of photochemical transformations and different reactors play a key role in such studies. This research domain builds a bridge between fundamental studies of organic photochemical reactions and their industrial application.

The In Vitro Antioxidant and Anti-Inflammatory Activities of Selected Australian Seagrasses.

Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (Zostera muelleri, Halodule uninervis, Cymodocea rotundata, Syringodium isoetifolium, and Thalassia hemprichii) from the Great Barrier Reef (QLD, Australia) were thus collected, and their preliminary antioxidant and anti-inflammatory activities were evaluated. From the acetone extracts of five seagrass species subjected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging antioxidant assay, the extract of Z. muelleri had the highest activity (half minimal concentration of inhibition (IC50) = 138 µg/mL), with the aerial parts (IC50 = 119 µg/mL) possessing significantly higher antioxidant activity than the roots (IC50 ≥ 500 µg/mL). A human peripheral blood mononuclear cells (PBMCs) assay with bacterial lipopolysaccharide (LPS) activation and LEGENDplex cytokine analysis showed that the aerial extract of Z. muelleri significantly reduced the levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 by 29%, 74%, and 90%, respectively, relative to the LPS treatment group. The aerial extract was thus fractionated with methanol (MeOH) and hexane fraction, and purification of the MeOH fraction by HPLC led to the isolation of 4-hydroxybenzoic acid (1), luteolin (2), and apigenin (3) as its major constituents. These compounds have been previously shown to reduce levels of TNF-α, IL-1ß, and IL-6 and represent some of the major bioactive components of Z. muelleri aerial parts. This investigation represents the first study of the antioxidant and anti-inflammatory properties of Z. muelleri and the first isolation of small molecules from this species. These results highlight the potential for using seagrasses in treating inflammation and the need for further investigation.

Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor.

[2 + 2]-Cycloadditions of cyclopentene and 2,3-dimethylbut-2-ene to furanone were investigated under continuous-flow conditions. Irradiations were conducted in a FEP-microcapillary module which was placed in a Rayonet chamber photoreactor equipped with low wattage UVC-lamps. Conversion rates and isolated yields were compared to analogue batch reactions in a quartz test tube. In all cases examined, the microcapillary reactor furnished faster conversions and improved product qualities.

Effects of aromatic hydrocarbons and evaluation of oil toxicity modelling for larvae of a tropical coral.

Application of oil toxicity modelling for assessing the risk of spills to coral reefs remains uncertain due to a lack of data for key tropical species and environmental conditions. In this study, larvae of the coral Acropora millepora were exposed to six aromatic hydrocarbons individually to generate critical target lipid body burdens (CTLBBs). Larval metamorphosis was inhibited by all six aromatic hydrocarbons, while larval survival was only affected at concentrations >2000 µg L-1. The derived metamorphosis CTLBB of 9.7 µmol g-1 octanol indicates larvae are more sensitive than adult corals, and places A. millepora larvae among the most sensitive organisms in the target lipid model (TLM) databases. Larvae were also more sensitive to anthracene and pyrene when co-exposed to ecologically relevant levels of ultraviolet radiation. The results suggest that the application of the phototoxic TLM would be protective of A. millepora larvae, provided adequate chemical and light data are available.

On the adsorption/photodegradation of amoxicillin in aqueous solutions by an integrated photocatalytic adsorbent (IPCA): experimental studies and kinetics analysis.

Activated carbon-supported TiO(2) nanoparticles, termed integrated photocatalytic adsorbents (IPCAs), were prepared using an ultrasonic impregnation technique and investigated for the photocatalytic degradation of amoxicillin (AMO), a ß-lactam antibiotic. The IPCAs had high adsorption affinity for AMO with the amount adsorbed proportional to the TiO(2) loading and the highest adsorption was at 10 wt% TiO(2) loading. A pseudo-second-order model was found to fit the experimental data and consistently predicted the amount of AMO adsorbed over the adsorption period. Equilibrium isotherm studies showed that the adsorption followed the Redlich-Peterson model with maximum adsorption capacity of 441.3 mg g(-1) for 10% IPCA, 23% higher than the pure activated carbon (AC). Kinetic studies on the photocatalytic degradation of AMO using non-linear regression analysis suggest that the degradation followed Langmuir-Hinshelwood (L-H) kinetics. The adsorption rate constant (K(ad)) was considerably higher than the photocatalytic rate constant (k(L-H)), indicating that the photocatalysis of AMO is the rate-determining step during the adsorption/photocatalysis process. The 10% IPCA exhibited excellent stability and reusability over four photodegradation cycles.

Microphotochemistry: a reactor comparison study using the photosensitized addition of isopropanol to furanones as a model reaction.

Three types of micro-photoreactor setups were investigated using DMBP-sensitized additions of isopropanol to furanones as model reactions. The results were compared to experiments using a conventional batch reactor. Based on conversion rates, reactor geometries and energy efficiency calculations the microsystems showed superior performances over the batch process. Of the three micro setups examined, the LED-driven microchip gave the best overall results.

Direct photooxidation and xanthene-sensitized oxidation of naphthols: quantum yields and mechanism.

The photoinduced oxidation of 1-naphthol to 1,4-naphthoquinone and of 5-hydroxy-1-naphthol to 5-hydroxy-1,4-naphthoquinone was studied by steady-state and time-resolved techniques. The direct photooxidation of naphthols in methanol or water takes place by reaction of the naphoxyl radical ((•)ONaph) with the superoxide ion radical (O(2)(•-)), the latter of which results from the reaction of the solvated electron with oxygen after photoionization. The sensitized oxidation takes place by energy transfer from the xanthene triplet state to oxygen. From the two oxygen atoms, which are consumed, one is incorporated into the naphthol molecule giving naphthoquinone and the second gives rise to water. The effects of eosin, erythrosin, and rose bengal in aqueous solution, pH, and the oxygen and naphthol concentrations were studied. The quantum yield of the photosensitized transformation was determined, which increases with the naphthol concentration and is largest at pH > 10. The quantum yield of oxygen uptake is similar. The pathway involving singlet molecular oxygen is suggested to operate for the three sensitizers. The alternative pathway via electron transfer from the naphthol to the xanthene triplet state and subsequent reaction of (•)ONaph with O(2)(•-), the latter of which is formed by scavenging of the xanthene radical anion by oxygen, does also contribute.

Recent advances in microflow photochemistry.

This review summarizes recent advances in microflow photochemical technologies and transformations. The portfolio of reactions comprises homogeneous and heterogeneous types, among them photoadditions, photorearrangements, photoreductions, photodecarboxylations, photooxygenations and photochlorinations. While microflow photochemistry is most commonly employed as a micro-scale synthesis tool, scale-up and technical production processes have already been developed.

Microphotochemistry: 4,4'-Dimethoxybenzophenone mediated photodecarboxylation reactions involving phthalimides.

A series of 4,4'-dimethoxybenzophenone mediated intra- and intermolecular photodecarboxylation reactions involving phthalimides have been examined under microflow conditions. Conversion rates, isolated yields and chemoselectivities were compared to analogous reactions in a batch photoreactor. In all cases investigated, the microreactions gave superior results thus proving the superiority of microphotochemistry over conventional technologies.

Photosensitized addition of isopropanol to furanones in a 365 nm UV-LED microchip.

The DMBP-sensitized addition of isopropanol to furanones was studied in a novel LED-driven microchip reactor. Complete conversions were achieved after just 2.5 to 5 min of irradiation with 6 × 365 nm high-power LEDs. The results were compared to analogous experiments using a conventional batch reactor.

The effects of ultraviolet radiation and climate on oil toxicity to coral reef organisms - A review.

Oil pollution remains a significant local threat to shallow tropical coral reef environments, but the environmental conditions typical of coral reefs are rarely considered in oil toxicity testing and risk assessments. Here we review the effects of three environmental co-factors on petroleum oil toxicity towards coral reef organisms, and show that the impacts of oil pollution on coral reef taxa can be exacerbated by environmental conditions commonly encountered in tropical reef environments. Shallow reefs are routinely exposed to high levels of ultraviolet radiation (UVR), which can substantially increase the toxicity of some oil components through phototoxicity. Exposure to UVR represents the most likely and harmful environmental co-factor reviewed here, leading to an average toxicity increase of 7.2-fold across all tests reviewed. The clear relevance of UVR co-exposure and its strong influence on tropical reef oil toxicity highlights the need to account for UVR as a standard practice in future oil toxicity studies. Indeed, quantifying the influence of UVR on toxic thresholds of oil to coral reef species is essential to develop credible oil spill risk models required for oil extraction developments, shipping management and spill responses in the tropics. The few studies available indicate that co-exposure to elevated temperature and low pH, both within the range of current daily and seasonal fluctuations and/or projected under continued climate change, can increase oil toxicity on average by 3.0- and 1.3-fold, respectively. While all three of the reviewed environmental co-factors have the potential to substantially increase the impacts of oil pollution in shallow reef environments, their simultaneous effects have not been investigated. Assessments of the combined effects of oil pollution, UVR, temperature and low pH will become increasingly important to identify realistic hazard thresholds suitable for future risk assessments over the coming century.

Use of Ca-alginate as a novel support for TiO2 immobilization in methylene blue decolorisation.

This study provides a preliminary contribution to the development of an industrial process for the UV/TiO(2) water treatment by introducing a novel support for TiO(2) immobilization. For the following study, Methylene Blue (MB) was chosen as the model dye to evaluate this novel immobilization system. The results showed that TiO(2) immobilized in a Ca-alginate bead retained its photoactivity during all of the experiments and the TiO(2)-gel beads presented good stability in water for maintaining its shape after several uses. When a proportion of 10% (v/v) of these beads was used, the configuration system demonstrated an improved mass transfer and consequently enhanced degradation efficiency. Experiments were also performed using 'recycled' beads. The results showed an increase in the degradation efficiency when the beads were reused, with an eventual 'self-destructive' effect. These studies showed great promise regarding the recyclable reagents with a reduction in waste at no greater cost or reduction in efficiency. Therefore, the potential of TiO(2)-gel beads as a simple and environmentally friendly catalyst for continuous use was developed.