Hemithioindigos for Cellular Photopharmacology: Desymmetrised Molecular Switch Scaffolds Enabling Design Control over the Isomer-Dependency of Potent Antimitotic Bioactivity.

Druglike small molecules with photoswitchable bioactivity-photopharmaceuticals-allow biologists to perform studies with exquisitely precise and reversible, spatial and temporal control over critical biological systems inaccessible to genetic manipulation. The photoresponsive pharmacophores disclosed have been almost exclusively azobenzenes, which has limited the structural and substituent scope of photopharmacology. More detrimentally, for azobenzene reagents, it is not researchers' needs for adapted experimental tools, but rather protein binding site sterics, that typically force whether the trans (dark) or cis (lit) isomer is the more bioactive. We now present the rational design of HOTubs, the first hemithioindigo-based pharmacophores enabling photoswitchable control over endogenous biological activity in cellulo. HOTubs optically control microtubule depolymerisation and cell death in unmodified mammalian cells. Notably, we show how the asymmetry of hemithioindigos allows a priori design of either Z- or E- (dark- or lit)-toxic antimitotics, whereas the corresponding azobenzenes are exclusively lit-toxic. We thus demonstrate that hemithioindigos enable an important expansion of the substituent and design scope of photopharmacological interventions for biological systems.

Hemiindigo: Highly Bistable Photoswitching at the Biooptical Window.

Hemiindigo is a long known chromophore that absorbs in the blue part of the spectrum but has almost completely been ignored as potential photoswitch. Herein we show how the absorption of hemiindigo is shifted to the red part of the visible spectrum and how nearly perfect photoswitching can be achieved using blue or green and red light. Five derivatives were investigated giving very high isomeric yields in both switching directions, i.e. >90% E isomer after irradiation with 470 to 530 nm light and 99% Z isomer with 590 up to 680 nm light. At the same time the thermal bistability is extraordinarily high leading to half-lives of the pure isomeric states of up to 83 years at 25 °C. The herein developed photoswitches show photochromism in the visible enabling the two isomeric states to be distinguished by the naked eye. Substituted hemiindigos therefore constitute extremely promising new photoswitches with excellent properties for applications in biology, chemistry, or material sciences.

Lethal and sub-lethal evaluation of Indigo Carmine dye and byproducts after TiO2 photocatalysis in the immune system of Eisenia andrei earthworms.

The Indigo carmine (IC) dye has been widely used in textile industries, even though it has been considered toxic for rats, pigs and humans. Owing to its toxicity, wastes containing this compound should be treated to minimize or eliminate their toxic effects on the biota. As an alternative to wastewater treatment, advanced oxidative processes (AOPs) have been highlighted due to their high capacity to destruct organic molecules. In this context, this study aimed to evaluate Indigo Carmine toxicity to soil organisms using the earthworm Eisenia andrei as a model-organism and also verify the efficiency of AOP in reducing its toxicity to these organisms. To this end, lethal (mortality) and sub-lethal (loss or gain of biomass, reproduction, behavior, morphological changes and immune system cells) effects caused by this substance and its degradation products in these annelids were evaluated. Morphological changes were observed even in organisms exposed to low concentrations, while mortality was the major effect observed in individuals exposed to high levels of indigo carmine dye. The organisms exposed to the IC during the contact test showed mortality after 72h of exposure (LC50 = 75.79mgcm-2), while those exposed to photoproducts showed mortality after 48h (LC50 = 243min). In the chronic study, the organisms displayed a mortality rate of 14%, while those exposed to the photoproduct reached up to 32.7%. A negative influence of the dye on the reproduction rate was observed, while by-products affected juvenile survival. A loss of viability and alterations in the cellular proportion was verified during the chronic test. However, the compounds did not alter the behavior of the annelids in the leak test (RL ranged from 20% to 30%). Although photocatalysis has been presented as an alternative technology for the treatment of waste containing the indigo carmine dye, this process produced byproducts even more toxic than the original compounds to E. andrei.

Composite nanofibers for highly efficient photocatalytic degradation of organic dyes from contaminated water.

In this study highly efficient photocatalyst based on composite nanofibers containing polyacrylonitrile (PAN), carbon nanotubes (CNT), and surface functionalized TiO2 nanoparticles was developed. The composite nanofibers were fabricated using electrospinning technique followed by chemical crosslinking. The surface modification and morphology changes of the fabricated composite nanofibers were examined through SEM, TEM, and FTIR analysis. The photocatalytic performance of the composite nanofibers for the degradation of model molecules, methylene blue and indigo carmine, under UV irradiation in aqueous solutions was investigated. The results demonstrated that high photodegradation efficiency was obtained in a short time and at low power intensity compared to other reported studies. The effective factors on the degradation of the dyes, such as the amount of catalyst, solution pH and irradiation time were investigated. The experimental kinetic data were fitted using pseudo-first order model. The effect of the composite nanofibers as individual components on the degradation efficiency of MB and IC was evaluated in order to understand the overall photodegradation mechanism. The results obtained showed that all the components possess significant effect on the photodegradation activity of the composite nanofibers. The stability studies demonstrated that the photodegradation efficiency can remain constant at the level of 99% after five consecutive cycles.

Photostability of 4,4'-dihydroxythioindigo, a mimetic of indigo.

The photochemical properties of indigo, a widely used industrial dye, has attracted both experimentalists and theoreticians from the beginning. Especially the high photostability of indigo has been the subject of intensive research. Recently, it was proposed that after photoexcitation an intramolecular proton transfer followed by a nonradiative relaxation to the ground state promote photostability. In indigo the hydrogen bond and the proton transfer occur between the opposing hemiindigo parts. Here, we provide experimental and theoretical evidence that a hydrogen transfer within one hemiindigo or hemithioindigo part is sufficient to attain photostability. This concept can serve as an interesting strategy towards new photostable dyes for the visible part of the spectrum.

Development of colorimetric ozone detection papers with high ultraviolet resistance using ultraviolet absorbers.

Two types of colorimetric ozone detection paper with high resistance to ultraviolet (UV) light have been developed for outdoor ozone detection. These detection papers incorporate indigo carmine and UV absorbers (UVAs). When exposed to ozone, the papers change color from blue to white, and the ozone concentration can be determined by measuring the reflectance of the papers. However, indigo carmine is strongly affected by UV light, thus making the papers unsuitable for outdoor ozone detection. The authors succeeded in sufficiently improving the resistance of the papers to UV light for them to be used outdoors. This was achieved by using hydrophilic UVAs, namely sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate and ferulic acid. Without a UVA, the maximum measurement error of the papers derived from UV effect is approximately 290 parts per billion (ppb) x hr when one assumes 8 hr of UV exposure at low- to mid-latitudes (approximately 60 Wh/m2), and this error is too great for accurate ozone measurement. In contrast, the measurement errors of the papers with UVAs are only approximately 60-70 ppb x hr under the same conditions. Ozone measurement accuracies of these detection papers with UVAs are +/- 4.3-4.5% (coefficient of variation [CV]) at 25 degrees C and 60% relative humidity without UV effect. As a result, the improved ozone detection paper with high resistance to UV rays is suitable for outdoor ozone measurements (e.g., for detecting photochemical oxidants).

Photolysis of Indigo Carmine solution by planar vacuum-ultraviolet (147 nm) light source.

Advanced oxidation processes (AOPs) are an attractive method to decompose dye-containing wastewaters, because they avoid issues of secondary pollution. In particular, a vacuum-ultraviolet (VUV) process is the simplest method, because an oxidation accelerator or a catalyst is not required. Conventional VUV sources with wavelengths of 185 nm or 172 nm have been used. We predicted that a shorter wavelength VUV process would have a higher ability to decompose dyes in wastewater. We developed a new planar light source that could emit a resonance line at 147 nm and a broad molecular line at 172 nm. The irradiance was 8.7 mW/cm2 at a distance of 20 mm from the emission surface to the UV power meter. We then conducted photocatalytic experiments of an Indigo Carmine solution at 3.33 × 10-4 mol/L to confirm the decomposition abilities of the developed light source, an excimer lamp of 172 nm and a Hg lamp of 254 nm. From the HPLC results, changes in Indigo Carmine concentration with the developed light source were equivalent to those with the excimer lamp. However, the residual ratio of total organic carbon (TOC) with the developed light source was lower than those with the other lamps. Therefore, a wavelength of 147 nm is superior to the conventional wavelength of 172 nm for Indigo Carmine decomposition. In addition, the developed light source emits VUV from only one side, which is a flat emitting surface. Consequently, the developed light source would have reduced manufacturing and maintenance costs compared to current VUV processing equipment.