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Journal of the American Chemical Society Jan 2020We accidentally found that YM-53601, a known small-molecule inhibitor of squalene synthase (SQS), selectively depletes SQS from mammalian cells upon UV irradiation....
We accidentally found that YM-53601, a known small-molecule inhibitor of squalene synthase (SQS), selectively depletes SQS from mammalian cells upon UV irradiation. Further analyses indicated that the photodepletion of SQS requires its short peptide segment located at the COOH terminus. Remarkably, when the 27 amino acid peptide was fused to green fluorescent protein or unrelated proteins at either the NH or COOH terminus, such fusion proteins were selectively depleted when the cells were treated with both YM-53601 and UV exposure. Product analysis and electron spin resonance experiments suggested that the UV irradiation promotes homolytic C-O bond cleavage of the aryl ether group in YM-53601. It is likely that the radical species generated from UV-activated YM-53601 abstract hydrogen atoms from the SQS peptide, leading to the photolysis of the entire protein. The pair of the SQS peptide and YM-53601 discovered in the present study paves the way for the design of a new small-molecule-controlled optogenetic tool.
Topics: Farnesyl-Diphosphate Farnesyltransferase; HEK293 Cells; Humans; Peptides; Photolysis; Quinuclidines
PubMed: 31899620
DOI: 10.1021/jacs.9b09178 -
Science Advances Jun 2022We combine novel laboratory experiments and exospheric modeling to reveal that "dynamic" Ly-α photolysis of Plutonian methane generates a photolytic refractory...
We combine novel laboratory experiments and exospheric modeling to reveal that "dynamic" Ly-α photolysis of Plutonian methane generates a photolytic refractory distribution on Charon that increases with latitude, consistent with poleward darkening observed in the New Horizons images. The flux ratio of the condensing methane to the interplanetary medium Ly-α photons, φ, controls the distribution and composition of Charon's photoproducts. Mid-latitude regions are likely to host complex refractories emerging from low-φ photolysis, while high-φ photolysis at the polar zones primarily generate ethane. However, ethane being colorless does not contribute to the reddish polar hue. Solar wind radiolysis of Ly-α-cooked polar frost past spring sunrise may synthesize increasingly complex, redder refractories responsible for the unique albedo on this enigmatic moon.
PubMed: 35714189
DOI: 10.1126/sciadv.abq5701 -
Spectrochimica Acta. Part A, Molecular... Mar 2024Conformational space of methoxyacetone (MA) was studied at the MP2/6-311++G(d,p) and DFT(B3LYP)/6-311++G(d,p) levels of theory. Computations predict MA to adopt four...
Conformational space of methoxyacetone (MA) was studied at the MP2/6-311++G(d,p) and DFT(B3LYP)/6-311++G(d,p) levels of theory. Computations predict MA to adopt four conformations, resulting from internal rotations around the O=C-C-O (Trans, Cis) and C-C-O-C (trans, gauche) dihedral angles. The Tt (Trans-trans) conformer is the most stable. The computed energies of two gauche (Tg and Cg) conformers fall in the 3-8 kJ mol range above Tt and should account for 1/3 of the room-temperature gas-phase equilibrium. The energy of Ct form is 11 kJ mol above Tt, and its expected population is negligible (below 1 %). In our earlier work, MA monomers were isolated in cryogenic argon matrices and characterized by infrared spectroscopy. In the experiment, only the most stable Tt conformer was detected in the sample. Signatures of the other conformers were not detected, either in freshly deposited samples, or in samples subjected to different UV irradiations. We rationalize those observations in terms of computed barriers for intramolecular torsions, indicating occurrence of conformational cooling during deposition. The experimental infrared spectrum of the Tt form is now assigned with the aid of anharmonic DFT computations. Exposure of MA to UV irradiation in the 300-260 nm range led to photolysis, according to the Norrish type II mechanism, resulting in dimer between enol acetone and formaldehyde observed as a cage-confined intermediate photoproduct. The subsequent photolysis resulted in the formation of carbon monoxide as the dominating photoproduct, formed in the Norrish type I photoreaction. Mechanistic interpretation of this photo decarbonylation reaction is presented.
PubMed: 38056186
DOI: 10.1016/j.saa.2023.123651 -
Purinergic Signalling Sep 2021Purinergic signaling plays a pivotal role in physiological processes and pathological conditions. Over the past decades, conventional pharmacological, biochemical, and... (Review)
Review
Purinergic signaling plays a pivotal role in physiological processes and pathological conditions. Over the past decades, conventional pharmacological, biochemical, and molecular biology techniques have been utilized to investigate purinergic signaling cascades. However, none of them is capable of spatially and temporally manipulating purinergic signaling cascades. Currently, optical approaches, including optopharmacology and optogenetic, enable controlling purinergic signaling with low invasiveness and high spatiotemporal precision. In this mini-review, we discuss optical approaches for controlling purinergic signaling and their applications in basic and translational science.
Topics: Adenosine Triphosphate; Animals; Humans; Optogenetics; Photolysis; Receptors, Purinergic; Signal Transduction
PubMed: 34156578
DOI: 10.1007/s11302-021-09799-2 -
ACS Omega Mar 2023The photolytic properties of -acyl-7-nitroindolines make these compounds attractive as photocleavable protecting groups and "caged" compounds for the light-induced...
The photolytic properties of -acyl-7-nitroindolines make these compounds attractive as photocleavable protecting groups and "caged" compounds for the light-induced release ("uncaging") of biologically active compounds and as acylating reagents under neutral conditions. However, the synthesis of -acyl-7-nitroindolines usually requires multiple steps, and the direct acylation of 7-nitroindolines can be quite challenging. 7-Nitroindolines with other types of -carbonyl-containing groups may also be photoreactive and could potentially be better accessible. Here we demonstrate the short and efficient synthesis of 5-bromo-7-nitroindoline--thiocarbamates, a new class of photoreactive compounds, and the study of some of their photochemical and photophysical properties. Using 5-bromo-7-nitroindoline--ethylthiocarbamate as a model compound, we show that it can undergo one-photon and two-photon photolysis at 350 and 710 nm, respectively. Our experimental data and quantum chemistry calculations support a photolysis pathway that differs from photolysis pathways previously reported for -acyl-7-nitroindolines. The photolysis with 350 nm light results in 5-bromo-7-nitrosoindoline, which is in equilibrium with its dimeric form(s), as supported by experiment and theory. This study expands the scope of photoreactive 7-nitroindoline derivatives and informs the development of novel photocleavable compounds.
PubMed: 36936343
DOI: 10.1021/acsomega.2c08184 -
Cells Nov 2023Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of... (Review)
Review
Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections, such as herpes and acne lesions, involves the synergistic use of specific light wavelengths and photosensitizers, like methylene blue. Photodynamic therapy, as it is termed, relies on the generation of antimicrobial reactive oxygen species (ROS) through the interaction between light and externally applied photosensitizers. Recent research, however, has highlighted the intrinsic antimicrobial properties of light itself, marking a paradigm shift in focus from exogenous agents to the inherent photosensitivity of molecules found naturally within pathogens. Chemical analyses have identified specific organic molecular structures and systems, including protoporphyrins and conjugated C=C bonds, as pivotal components in molecular photosensitivity. Given the prevalence of these systems in organic life forms, there is an urgent need to investigate the potential impact of phototherapy on individual molecules expressed within pathogens and discern their contributions to the antimicrobial effects of light. This review delves into the recently unveiled key molecular targets of phototherapy, offering insights into their potential downstream implications and therapeutic applications. By shedding light on these fundamental molecular mechanisms, we aim to advance our understanding of phototherapy's broader therapeutic potential and contribute to the development of innovative treatments for a wide array of microbial infections and diseases.
Topics: Humans; Photosensitizing Agents; Phototherapy; Photochemotherapy; Anti-Infective Agents; Acne Vulgaris
PubMed: 37998399
DOI: 10.3390/cells12222664 -
Journal of Personalized Medicine Sep 2022Reactive oxygen species (ROS) and free radicals, which have been implicated in inflammation, pain, carcinogenesis, and aging, are actually used in dental treatments such... (Review)
Review
Reactive oxygen species (ROS) and free radicals, which have been implicated in inflammation, pain, carcinogenesis, and aging, are actually used in dental treatments such as tooth bleaching and composite resin polymerization. Recently, numerous studies have investigated the application of ROS in the medical and dental fields. In previous studies, ROS were generated intentionally through pathways such as photolysis, photocatalytic methods, and photodynamic therapy, which are used in the medical field to target cancer. In the field of dentistry, generated ROS are applied mainly for periodontal treatment and sterilization of the root canal, and its effectiveness as an antibacterial photodynamic therapy has been widely reported.. Given this background, the present article aimed to review the basic effects of ROS in dental medicine, especially endodontic therapy, and to discuss future applications of ROS.
PubMed: 36143315
DOI: 10.3390/jpm12091531 -
ACS ES&T Water Mar 2023Insensitive munitions formulations that include 3-nitro-1,2,4-triazol-5-one (NTO) are replacing traditional explosive compounds. While these new formulations have...
Insensitive munitions formulations that include 3-nitro-1,2,4-triazol-5-one (NTO) are replacing traditional explosive compounds. While these new formulations have superior safety characteristics, the compounds have greater environmental mobility, raising concern over potential contamination and cleanup of training and manufacturing facilities. Here, we examine the mechanisms and products of NTO photolysis in simulated sunlight to further inform NTO degradation in sunlit surface waters. We demonstrate that NTO produces singlet oxygen and that dissolved oxygen increases the NTO photolysis rate in deionized water. The rate of NTO photolysis is independent of concentration and decreases slightly in the presence of Suwannee River Natural Organic Matter. The apparent quantum yield of NTO generally decreases as pH increases, ranging from 2.0 × 10 at pH 12 to 1.3 × 10 at pH 2. Bimolecular reaction rate constants for NTO with singlet oxygen and hydroxyl radical were measured to be (1.95 ± 0.15) × 10 and (3.28 ± 0.23) × 10 M s, respectively. Major photolysis reaction products were ammonium, nitrite, and nitrate, with nitrite produced in nearly stoichiometric yield upon the reaction of NTO with singlet oxygen. Environmental half-lives are predicted to span from 1.1 to 5.7 days. Taken together, these data enhance our understanding of NTO photolysis under environmentally relevant conditions.
PubMed: 36936519
DOI: 10.1021/acsestwater.2c00567 -
ChemistryOpen Aug 2020Bioorthogonal reactions including the bioorthogonal ligations and cleavages have become an active field of research in chemical biology, and they play important roles in... (Review)
Review
Bioorthogonal reactions including the bioorthogonal ligations and cleavages have become an active field of research in chemical biology, and they play important roles in chemical modification and functional regulation of biomolecules. This review summarizes the developments and applications of the representative bioorthogonal reactions including the Staudinger reactions, the metal-mediated bioorthogonal reactions, the strain-promoted cycloadditions, the inverse electron demand Diels-Alder reactions, the light-triggered bioorthogonal reactions, and the reactions of chloroquinoxalines and -dithiophenols.
Topics: Alkynes; Azides; Catalysis; Cycloaddition Reaction; Heterocyclic Compounds, 1-Ring; Light; Metals, Heavy; Phosphines; Photolysis; Quinoxalines; Sulfhydryl Compounds
PubMed: 32817809
DOI: 10.1002/open.202000128 -
Ecotoxicology and Environmental Safety Jun 2023Triclosan (TCS) is omnipresent in the environment and has drawn increasing attention due to its potential adverse effects on human health. Direct photolysis of TCS...
Triclosan (TCS) is omnipresent in the environment and has drawn increasing attention due to its potential adverse effects on human health. Direct photolysis of TCS readily occurs, especially in the surface layers of waters that receive abundant ultraviolet radiation during the daytime. However, biological concerns and the identification of toxic products during TCS photolysis have been explored limitedly. Therefore, in the present work, the structural characterization of the photolysis products by UVC and UVA were performed based on the mass spectra and fragmental ions. The results displayed that TCS was more readily eliminated by UVC than UVA, and the product species were completely different when TCS was degraded by UVC and UVA, respectively. Two products, m/z 235 and m/z 252, were produced via reductive dechlorination and nucleophilic substitution with UVC, while three dioxin-like isomer products were generated by dechlorination, cyclization and hydroxylation. Furthermore, the results of biological concerns suggested that the elimination of TCS did not represent the disappearance of biological risks. Specifically, more hazardous and photolysis products were formed during TCS photolysis with ultraviolets. For instance, the dioxin-like isomer products were highly microtoxic and genotoxic, and mildly antiestrogenic. The positive findings highlighted the biological concerns of TCS photolysis by ultraviolet radiation in the aquatic environment.
Topics: Humans; Triclosan; Ultraviolet Rays; Photolysis; Dioxins; Mass Spectrometry; Water Pollutants, Chemical
PubMed: 37167739
DOI: 10.1016/j.ecoenv.2023.114998