Water-Soluble Organic Nanoparticles with Programable Intermolecular Charge Transfer for NIR-II Photothermal Anti-Bacterial Therapy.

Extensive recent efforts have been put on the design of high-performance organic near-infrared (NIR) photothermal agents (PTAs), especially over NIR-II bio-window (1000-1350 nm). So far, the development is mainly limited by the rarity of molecules with good NIR-II response. Here, we report organic nanoparticles of intermolecular charge-transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR-I to NIR-II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red-shifted absorption peak at 1040 nm and achieves a good photothermal conversion efficiency of 42 % under 1064 nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram-negative and Gram-positive bacteria. This work opens a new avenue into the development of efficient PTAs.

Two-photon uncaging of bioactive thiols in live cells at wavelengths above 800 nm.

Photoactivatable protecting groups (PPGs) are useful for a broad range of applications ranging from biology to materials science. In chemical biology, induction of biological processes via photoactivation is a powerful strategy for achieving spatiotemporal control. The importance of cysteine, glutathione, and other bioactive thiols in regulating protein structure/activity and cell redox homeostasis makes modulation of thiol activity particularly useful. One major objective for enhancing the utility of photoactivatable protecting groups (PPGs) in living systems is creating PPGs with longer wavelength absorption maxima and efficient two-photon (TP) absorption. Toward these objectives, we developed a carboxyl- and dimethylamine-functionalized nitrodibenzofuran PPG scaffold (cDMA-NDBF) for thiol photoactivation, which has a bathochromic shift in the one-photon absorption maximum from λmax = 315 nm with the unfunctionalized NDBF scaffold to λmax = 445 nm. While cDMA-NDBF-protected thiols are stable in the presence of UV irradiation, they undergo efficient broad-spectrum TP photolysis at wavelengths as long as 900 nm. To demonstrate the wavelength orthogonality of cDMA-NDBF and NDBF photolysis in a biological setting, caged farnesyltransferase enzyme inhibitors (FTI) were prepared and selectively photoactivated in live cells using 850-900 nm TP light for cDMA-NDBF-FTI and 300 nm UV light for NDBF-FTI. These experiments represent the first demonstration of thiol photoactivation at wavelengths above 800 nm. Consequently, cDMA-NDBF-caged thiols should have broad applicability in a wide range of experiments in chemical biology and materials science.

Emergence of light-driven protometabolism on recruitment of a photocatalytic cofactor by a self-replicator.

Establishing how life can emerge from inanimate matter is among the grand challenges of contemporary science. Chemical systems that capture life's essential characteristics-replication, metabolism and compartmentalization-offer a route to understanding this momentous process. The synthesis of life, whether based on canonical biomolecules or fully synthetic molecules, requires the functional integration of these three characteristics. Here we show how a system of fully synthetic self-replicating molecules, on recruiting a cofactor, acquires the ability to transform thiols in its environment into disulfide precursors from which the molecules can replicate. The binding of replicator and cofactor enhances the activity of the latter in oxidizing thiols into disulfides through photoredox catalysis and thereby accelerates replication by increasing the availability of the disulfide precursors. This positive feedback marks the emergence of light-driven protometabolism in a system that bears no resemblance to canonical biochemistry and constitutes a major step towards the highly challenging aim of creating a new and completely synthetic form of life.

[The effect of low dose ionizing radiation exposure on dynamic thiol-disulfide homeostasis and ischemia modified albumin levels: an observational study]. / Efeito da exposição à radiação ionizante de baixa dose na homeostase dinâmica de tiol­dissulfeto e níveis de albumina modificada por isquemia: estudo observacional.

BACKGROUND: The primary objective of this study was to investigate the effect of low dose ionizing radiation exposure on thiol/disulfide homeostasis and ischemia modified albumin levels. The secondary objective is to compare thiol/disulfide homeostasis and ischemia modified albumin levels among the personnel exposed to low dose ionizing radiation in anesthesia application areas, in and out of the Operation room. METHODS: The study included a total of 90 volunteers aged between 18 and 65 years old, with 45 personnel working in a setting with potential for radiation exposure (Exposed Group) and 45 personnel in a setting without radiation exposure (Control Group). Their native thiol, total thiol, disulphide, albumine and IMA levels were measured. Exposed group included personnel who were exposed to radiation outside the operating room - Operation room (-) Group and inside the Operating room - Operation room (+) Group. RESULTS: Albumin, native and total thiol levels were significantly lower in the participants exposed to radiation in the anesthesia application area, no statistically significant difference was found in terms of disulfide and ischemia modified albumin levels. In the Operation room (-) group exposed to radiation, native thiol and total thiol values were significantly lower compared to the Operation room (+) groups. CONCLUSION: Awareness of being in danger of oxidative stress should be established in personnel exposed to radiation in the anesthesia application area following low dose ionizing radiation exposure, and the necessary measures should be taken.

The effect of low dose ionizing radiation exposure on dynamic thiol-disulfide homeostasis and ischemia modified albumin levels: an observational study / Efeito da exposição à radiação ionizante de baixa dose na homeostase dinâmica de tiol-dissulfeto e níveis de albumina modificada por isquemia: estudo observacional

Abstract Background: The primary objective of this study was to investigate the effect of low dose ionizing radiation exposure on thiol/disulfide homeostasis and ischemia modified albumin levels. The secondary objective is to compare thiol/disulfide homeostasis and ischemia modified albumin levels among the personnel exposed to low dose ionizing radiation in anesthesia application areas, in and out of the operation room. Methods: The study included a total of 90 volunteers aged between 18 and 65 years old, with 45 personnel working in a setting with potential for radiation exposure (Exposed Group) and 45 personnel in a setting without radiation exposure (Control Group). Their native thiol, total thiol, disulphide, albumine and IMA levels were measured. Exposed group included personnel who were exposed to radiation outside the operating room - Operation room (−) Group and inside the operating room - Operation room (+) Group. Results: Albumin, native and total thiol levels were significantly lower in the participants exposed to radiation in the anesthesia application area; no statistically significant difference was found in terms of disulfide and ischemia modified albumin levels. In the Operation room (−) Group exposed to radiation, native thiol and total thiol values were significantly lower compared to the Operation room (+) Group. Conclusion: Awareness of being in danger of oxidative stress should be established in personnel exposed to radiation in the anesthesia application area following low dose ionizing radiation exposure, and the necessary measures should be taken.

Resumo Justificativa: O objetivo principal do estudo foi investigar o efeito de exposição à radiação ionizante de baixa dose nos níveis de homeostase tiol/dissulfeto e de albumina modificada por isquemia. O objetivo secundário foi comparar os níveis de homeostase tiol/dissulfeto e albumina modificada por isquemia entre indivíduos expostos à radiação ionizante de baixa dose nas áreas de procedimentos anestésicos, dentro e fora da sala de cirurgia. Método: O estudo incluiu um total de 90 voluntários com idades entre 18 e 65 anos, 45 profissionais que trabalhavam em ambiente de exposição potencial a radiação (Grupo Exposto) e 45 profissionais que trabalhavam em ambiente sem exposição à radiação (Grupo Controle). Foram medidos os níveis de tiol nativo, tiol total, dissulfeto, albumina e albumina modificada por isquemia. O Grupo Exposto era constituído por profissionais expostos a radiação fora da sala de cirurgia - Grupo sala de cirurgia (-) e na sala de cirurgia - Grupo sala de cirurgia (+). Resultados: Os níveis de albumina, tiol nativo e total foram significantemente mais baixos nos participantes expostos à radiação em área de realização de anestesia, e nenhuma diferença estatisticamente significante foi encontrada para os níveis de dissulfeto e albumina modificada por isquemia. No Grupo exposto sala de cirurgia (-), os valores de tiol nativo e tiol total foram significantemente mais baixos quando comparados ao Grupo sala de cirurgia (+). Conclusões: Os profissionais expostos à radiação em área de realização de anestesia devem ser conscientizados quanto ao perigo do estresse oxidativo após exposição à radiação ionizante de baixa dose e medidas cabíveis devem ser instituídas.

Rapid Buildup Arrays with Orthogonal Biochemistry Gradients via Light-Induced Thiol-Ene "Click" Chemistry for High-Throughput Screening of Peptide Combinations.

The concept of high-throughput screening sheds new light on fabrication and analysis of materials. Herein, a combinatorial surface-modified platform with biochemical gradients was developed through thiol-ene "click" chemistry by adjusting the intensity of ultraviolet (UV) irradiation. Contact angle, X-ray photoelectron spectroscopy, and ellipsometry measurement results demonstrated that the sulfhydryl molecules including polyethylene glycol and RGD (arginine-glycine-aspartic acid) and REDV (arginine-glutamic acid-aspartic acid-valine) peptides can be directly attached onto alkene-modified substrates, in which the graft density can be well controlled by the intensity of UV irradiation. The multistep attachment of different molecules onto substrates is archived via the multistep UV-initiated thiol-ene "click" reaction. The high-throughput arrays with the gradient density of single ligand and the orthogonal gradient density of two ligands were rapidly fabricated via the one-step UV gradient irradiation and the two-step orthogonal UV gradient-initiated thiol-ene "click" reaction. Endothelial cells (ECs) and smooth muscle cells (SMCs) were cocultured on the array with the orthogonal gradient density of RGD and REDV to screen the peptide combination with high EC selectivity, which is essential for in situ endothelialization during stent implant. From 64, 8 × 8, combinations investigated, a special combinatorial surface representing the really high competitiveness of ECs over SMCs was screened. This platform puts forward a facile, high-throughput method to study the combinatorial variation of biochemical signals to cell behavior.

Metal-free synthesis of imino-disaccharides and calix-iminosugars by photoinduced radical thiol-ene coupling (TEC).

Radical thiol-ene coupling was exploited for the first time to prepare imino-disaccharides and multivalent iminosugars starting from sugar thiols and iminosugar alkenes or iminosugar thiols and tetra-allylated calixarene, respectively.

Direct monitoring of light mediated hyperthermia induced within mammalian tissues using surface enhanced spatially offset Raman spectroscopy (T-SESORS).

Here we demonstrate light mediated heating of nanoparticles confined deep inside mammalian tissue, whilst directly monitoring their temperature non-invasively using a form of deep Raman spectroscopy, T-SESORS. One of the main barriers to the introduction of photo-thermal therapies (PTT) has been recognised as the inability to directly monitor the local temperature deep within the tissue at the point of therapy. Here Au nanoparticles with a Raman reporter molecule (temperature reporters) are used in combination with Au nanoshells (heat mediators) to provide simultaneously heating under NIR illumination and direct spectroscopic monitoring of local temperature deep within mammalian tissues. The surface enhanced Raman signal was read out at the tissue surface using a transmission geometry in this example and the temperature of the tissue was ascertained from the anti-Stokes to Stokes Raman reporter. This approach opens the prospect of non-invasive hyperthermia treatments with direct temperature feedback from deep inside within tissue, where nanoparticles can be used to both provide localised heating and accurately monitor the local temperature.

The impact of postharvest ultra-violet light irradiation on the thiol content of Sauvignon blanc grapes.

Sauvignon blanc grapes were exposed to an ultra-violet (UV) light source post-hand harvest (whole bunches) or post-machine harvest. The thiol precursors S-3-(hexan-1-ol)-l-cysteine (Cys-3MH) and S-3-(hexan-1-ol)-l-glutathione (GSH-3MH) were quantified in the juices before and after UV treatment. Results showed that irradiation of the grapes with UV light had little to no effect on the thiol precursors. Wines were fermented from the corresponding juices and 18 aroma compounds were quantified. Differences were found between UV treatments of the wines for 3-mercaptohexanol, hexan-1-ol, ethyl butanoate, ethyl hexanoate, ethyl octanoate and phenylethyl alcohol. However, these changes were not significant (p < 0.05) for both grape media trialled. Future studies involving larger sample sizes and replicate numbers should be completed in order to ascertain any changes in aroma chemistry as a result of UV light application to grapes postharvest.

Thiol-ene click chemistry towards easy microarraying of half-antibodies.

A UV light-induced thiol-ene coupling reaction (TEC) between half-antibodies (hIgG) and vinyl functionalized glass surfaces was run for biosensing in the microarray format. The accomplished performance improved that obtained with whole antibodies.

Probing the DOM-mediated photodegradation of methylmercury by using organic ligands with different molecular structures as the DOM model.

Photodegradation is the main depletion pathway for methylmercury (MeHg) in surface water. The formation of MeHg-dissolved organic matter (DOM) complexes has been found to be a key step in MeHg photodegradation. However, the major functional groups involved in the DOM-mediated process have yet to be clearly resolved. In this work, we systematically investigated the effects of DOM molecular structures on MeHg photodegradation by using a variety of organic ligands with different functional groups (e.g., thiosalicylate, thiophenol, and thioaniline). The results showed that thiol and phenyl groups may be the major functional groups governing DOM-mediated MeHg photodegradation, with photodegradation rates also dependent on the type (carboxyl, hydroxyl, and amino group) and position (ortho-, meta-, and para-) of other chemical substituents. The addition of "non-photochemically active" thiol ligands (e.g., mercaptoethanol and dithiothreitol) and high concentrations of Cl- can significantly inhibit the o-thiosalicylate-induced MeHg photodegradation, indicating that complexation of MeHg with these ligands is necessary for MeHg photodegradation. Sparging with O2 had a negligible effect on MeHg photodegradation, while sparging with N2 significantly enhanced MeHg photodegradation. This finding suggests that MeHg photodegradation may be a reductive process, which was further supported by identification of the degradation products of MeHg. A possible protonolysis mechanism of MeHg photodegradation in the presence of o-thiosalicylate was then proposed based on the findings of this study.

A near-infrared fluorescent probe for sensitive detection and imaging of sulfane sulfur in living cells and in vivo.

Sulfane sulfur refers to ionized sulfur that is reversibly attached to other sulfur atoms in the form of 6-valence electrons (S0). Sulfane sulfur possesses stronger nucleophilicity and reducibility than hydrogen sulfide in a series of physiological reactions, which probably makes sulfane sulfur the actual signal molecule in cells. Herein, we designed and synthesized a near-infrared (NIR) fluorescent probe BD-diSH for sensitive detection and imaging of sulfane sulfur in living cells and in vivo. The probe BD-diSH is composed of two moieties: the fluorophore azo-BODIPY and the sulfane sulfur recognition unit, viz., 2-mercapto benzoate. BD-diSH displayed high sensitivity and selectivity towards sulfane sulfur. The mercapto group (-SH) of 2-mercapto benzoic acid can nucleophilically capture the sulfur atom of thiosulfoxide tautomers in sulfane sulfur to form -SSH. The group -SSH will immediately induce intramolecular cyclization reaction and release the azo-BODIPY fluorophore to emit NIR fluorescence. The probe BD-diSH was successfully applied to detect and image sulfane sulfur in the cytoplasm of the living cells. The results illustrated that the endogenous and exogenous sulfane sulfur level changed depending on different cell lines. BD-diSH was also capable of imaging the level changes of sulfane sulfur in mice. The above applications make our new probe a potential chemical tool for the study of physiological and pathological functions of sulfur sulfide in living cells and in vivo.

Microdosimetric Modeling of Biological Effectiveness for Boron Neutron Capture Therapy Considering Intra- and Intercellular Heterogeneity in 10B Distribution.

We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in 10B distribution. The new model was developed from our previously established stochastic microdosimetric kinetic model that determines the surviving fraction of cells irradiated with any radiations. In the model, the probability density of the absorbed doses in microscopic scales is the fundamental physical index for characterizing the radiation fields. A new computational method was established to determine the probability density for application to BNCT using the Particle and Heavy Ion Transport code System PHITS. The parameters used in the model were determined from the measured surviving fraction of tumor cells administrated with two kinds of 10B compounds. The model quantitatively highlighted the indispensable need to consider the synergetic effect and the dose dependence of the biological effectiveness in the estimate of the therapeutic effect of BNCT. The model can predict the biological effectiveness of newly developed 10B compounds based on their intra- and intercellular distributions, and thus, it can play important roles not only in treatment planning but also in drug discovery research for future BNCT.

Aquatic indirect photochemical transformations of natural peptidic thiols: impact of thiol properties, solution pH, solution salinity and metal ions.

Natural peptidic thiols play numerous important roles in aquatic systems. While thiols are known to be susceptible to sensitized photoreaction, the photochemical transformation of thiols in surface waters remains largely unknown. This study systematically assessed the photochemical transformation of naturally occurring thiols, including arginylcysteine (RC), γ-glutamylcysteine (γEC), glutathione (GSH), and phytochelatin (PC) in solutions containing dissolved organic matter (DOM). The results show that all thiols underwent rapid indirect photochemical transformation. The transformation rates of thiols were highly pH-dependent and increased with increasing solution pH. γEC and GSH show lower transformation rates than free Cys, which was ascribed to their higher thiol pKa values. In comparison, PC and RC show much higher transformation rates than γEC and GSH, due to more reactive thiol groups contained in the PC molecule and sorption of RC to DOM macromolecules, respectively. While all investigated pathways contributed to thiol transformation, hydroxyl radical-mediated oxidation dominated at low solution pH and singlet oxygen-mediated oxidation dominated at high solution pH in the DOM-sensitized phototransformations of γEC, GSH, and PC. Furthermore, the effects of metal complexation and solution salinity on thiol transformation rates were examined. Thiol reactivity was not affected by Fe3+ and Ag+, slightly enhanced in the presence of Zn2+, Cd2+ and Hg2+, and significantly enhanced by Cu2+. Additionally, enhanced thiol transformation rates were observed in solutions with high salinity.

Photocrosslinking of styrene-butadiene-styrene (SBS) networks formed by thiol-ene reactions and their influence on cell survival.

Styrene-butadiene-styrene (SBS) triblock copolymer has been conventionally used as synthetic rubber. However, the potential of SBS for biomedical applications has only been considered in limited earlier reports. Here, we demonstrate an effective approach to designing a photocrosslinked SBS network. Rheological analysis has been conducted for the investigation of the storage modulus of the resultant network. Crosslinked SBS networks were synthesized and characterized through optical and electron microscope imaging. The crosslink density of the network, calculated from swelling experiments, was 643 mol m(-3), where higher swelling in a hydrophobic medium was observed compared to the swelling measured in water. Cell survival analysis with HeLa cells and NIH/3T3 fibroblasts revealed that these networks are non-toxic, and that they could be considered for a variety of biomedical applications.

Modular modification of xylan with UV-initiated thiol-ene reaction.

Birch xylan was functionalized with various thiols through UV initiated radical thiol-ene reaction under mild conditions. Xylan was allylated through etherification with allyl glycidyl ether under alkaline conditions. The allylated xylan was then reacted with thiols containing varying functional groups: trimethylbenzyl mercaptan, dodecanethiol, thioglycolic acid, L-cysteine and cysteamine hydrochloride. The reactions were conducted under homogeneous conditions at room temperature, either in water (hydrophilic thiols) or in DMF (hydrophobic thiols). The effect of reaction parameters to the functionalization efficiency was studied, including, for example, thiol excess, thiol character, initiator amount and reaction mixture concentration. The reactions were fast and 100% conversion of allyl groups was reached in most cases, sometimes already within 10 min. Water as solvent resulted generally in faster reactions when compared to DMF, and it was possible to conduct the aqueous reaction even without added UV initiator. It was also possible to incorporate two functionalities simultaneously during one reaction into the xylan structure.

Visible-light-initiated thiol-acrylate photopolymerization of heparin-based hydrogels.

An in situ heparin-based forming hydrogel that cures under visible-light is formulated using eosin Y as a photoinitiator with triethanolamine as an electron donor to initiate reaction of thiolated-heparin with acrylate-ended poly(ethylene glycol). Formulations and irradiation conditions are presented for control of heparin content (1.6 to 3.3% w/v), modulus (100-10,000 Pa), and gelation time (30-600 s). Encapsulation of 3T3 fibroblasts in the hydrogel gave over 96% viability for all conditions examined. In vitro characterization of epidermal growth factor released from the hydrogel confirmed that the growth factor remains bioactive. The ability to deliver growth factors, fast gelation kinetics under visible light, and independent control of physical and biochemical properties makes this system a promising candidate for use in regenerative medicine. In particular, irradiation conditions that achieve gelation in 150s are compatible with the stringent light exposure limits of the retina, which affords a wide safety margin for use with other tissues.

Surfactant-free coating of thiols on gold nanoparticles using sonochemistry: a study of competing processes.

A method for the surfactant-free coating of gold nanoparticles with thiols using sonochemistry is presented. The gold nanoparticles were prepared by a modified Zsigmondy method, affording good control over the particle-size distribution, and the thiol coating was performed by the sonication of a biphasic system consisting of a nanoparticle suspension in water and thiols in toluene. The effects of two important reaction parameters on the particle morphology, viz. sonication time and thiol concentration, were investigated in detail using transmission electron microscopy. The effect of the thiol chain length was also studied. We show that the morphology of the coated particles is determined through a competition between two opposing effects: particle fusion, due to the sonication conditions, and digestive ripening, due to the action of the thiols. Additionally, we illustrate the utility of our technique for various applications, including surface-enhanced Raman scattering from bound molecules, and further functionalization using a thiol-exchange reaction. Our technique paves the way for an efficient synthesis of thiol-coated AuNPs of different shapes and sizes, suitable for a range of diverse applications.

[Influence of extremely low frequency magnetic field on total protein and -sh groups concentrations in liver homogenates]. / Wplyw pola magnetycznego ekstremalnie niskiej czestotliwosci na zawartosc bialka calkowitego oraz grup-SH w homogenatach watroby.

BACKGROUND: Free radicals are atoms, molecules or their fragments, whose excess leads to the development of oxidative stress, the cause of many neoplastic, neurodegenerative and inflammatory diseases, as well as aging of organisms. Industrial pollution, tobacco smoke, ionizing radiation, ultrasound and magnetic fields are the major exogenous sources of free radicals. The low frequency mag- netic field is commonly applied in physiotherapy. The aim of the present study was to evaluate the effect of extremely low frequency magnetic field (1L.F-MF) on the concentration ofsullhydryl groups (-SH) and proteins in liver tissues of experimental animals de- pending on the time of exposure to the field. MATERIAL AND METHODS: Twenty one Sprague-D)awley male rats, aged 3-4 months were randomly divided into 3 experimental groups (each containing 7 animals): controls (group I), the rats exposed to IEI.F-MF of 40 Hz, 7 mT (this kind of the ELF-MF is mostly used in magnetotherapy), 30 min/day for 2 weeks (group II) and the rats exposed to 40 Hz, 7 mT for 60 min/day for 2 weeks (group III). The concentrations of proteins and sulfhydryl groups in the liver tissues were determined after exposure to magnetic fields. RESULTS: Exposure to low magnetic field: 40 Hz, 7 mT for 30 min/day and 60 min/day for 2 weeks caused a significant increase in the concentration of-SH groups and total protein levels in the liver tissues. CONCLUSIONS: The study results suggest that exposure to magnetic fields leads to the development of adaptive mechanisms to maintain the balance in the body oxidation-reduction and in the case of the studied parameters does not depend on the time of exposure.