Efficient Oxidation and Destabilization of Zn(Cys)4 Zinc Fingers by Singlet Oxygen

Singlet oxygen (¹O₂) plays an important role in oxidative stress in all types of organisms, most of them being able to mount a defense against this oxidant. Recently, zinc finger proteins have been proposed to be involved in its cellular detection but the molecular basis of this process still remains unknown. We have studied the reactivity of a Zn(Cys)₄ zinc finger with ¹O₂ by combinations of spectroscopic and analytical techniques, focusing on the products formed and the kinetics of the reaction. We report that the cysteines of this zinc finger are oxidized to sulfinates by ¹O₂. The reaction of the ZnS₄ core with ¹O₂ is very fast and efficient with almost no physical quenching of ¹O₂. A drastic (ca. five orders of magnitude) decrease of the Zn²⁺ binding constant was observed upon oxidation. This suggests that the Zn(Cys)₄ zinc finger proteins would release their Zn²⁺ ion and unfold upon reaction with ¹O₂ under cellular conditions and that zinc finger sites are likely targets for ¹O₂.     

DNA-Triggered Enhancement of Singlet Oxygen Production by Pyridinium Alkynylanthracenes

There is an ongoing interest in ¹O₂ sensitizers, whose activity is selectively controlled by their interaction with DNA. To this end, we synthesized three isomeric pyridinium alkynylanthracenes 2 o – p and a water-soluble trapping reagent for ¹O₂. In water and in the absence of DNA, these dyes show a poor efficiency to sensitize the photooxygenation of the trapping reagent as they decompose due to electron transfer processes. In contrast, in the presence of DNA ¹O₂ is generated from the excited DNA-bound ligand. The interactions of 2 o – p with DNA were investigated by thermal DNA melting studies, UV/vis and fluorescence spectroscopy, and linear and circular dichroism spectroscopy. Our studies revealed an intercalative binding with an orientation of the long pyridyl-alkynyl axis parallel to the main axis of the DNA base pairs. In the presence of poly(dA : dT), all three isomers show an enhanced formation of singlet oxygen, as indicated by the reaction of the latter with the trapping reagent. With green light irradiation of isomer 2 o in poly(dA : dT), the conversion rate of the trapping reagent is enhanced by a factor >10. The formation of ¹O₂ was confirmed by control experiments under anaerobic conditions, in deuterated solvents, or by addition of ¹O₂ quenchers. When bound to poly(dG : dC), the opposite effect was observed only for isomers 2 o and 2 m , namely the trapping reagent reacted significantly slower. Overall, we showed that pyridinium alkynylanthracenes are very useful intercalators, that exhibit an enhanced photochemical ¹O₂ generation in the DNA-bound state.     

Synthesis,DNA binding mode,singlet oxygen photogeneration and DNA photocleavage activity of ruthenium compounds with porphyrin–imidazo[4,5‐f]phenanthroline conjugated ligand

Using 1,10‐phenanothroline‐5,6‐dione and 10,20‐bis(4‐methylphenyl)porphyrin copper as starting materials, a conjugated porphyrin–imidazo[4,5‐f]‐1,10‐phenanothroline ligand (Por 1 ) was prepared. Subsequently, the copper complex of Por 1 was reacted with Ru(1,10‐phenanothroline)₂Cl₂ to yield ruthenium compound Por 2 . After removal of copper metal under acid condition, the free base porphyrin of Por 2 (Por 3 ) was prepared. The structure of these compounds was confirmed using UV–visible, ¹H NMR, mass and infrared spectroscopies and elemental analysis. Through UV–visible, fluorescence and circular dichroism analyses, the interaction modes between Por 1 – 3 and calf thymus DNA were investigated. Por 1 interacted with DNA via outside groove face, but Por 2 and Por 3 showed intercalative interaction with DNA. Binding constants between Por 1 – 3 and DNA were 7.79 × 10⁵, 1.29 × 10⁶ and 1.32 × 10⁶ M^?1, respectively. With 5,10,15,20‐tetraphenylporphyrin (H₂TPP) as a control, the singlet oxygen (¹O₂) generation of Por 1 – 3 was measured using the 1,3‐diphenylisobenzofuran method. The ¹O₂ generation rate of Por 1 – 3 followed the order: Por 3 >Por 1 >H₂TPPP >Por 2 . Por 1 and Por 3 showed better ¹O₂ quantum yields than Por 2 , which were almost threefold higher than that of H₂TPP. The DNA cleavage ability of Por 1 – 3 was analyzed using gel electrophoresis. Por 3 showed higher DNA photocleavage activity, with more than 50% photocleavage rate at 20 μM. These results suggest that amphipathic (hydrophilic/lipophilic) Por 3 with conjugated Por 1 ligand is a potential photosensitizer in cancer therapy.     

Mechanism of the O2(1Δg) generation from the Cl2/H2O2 basic aqueous solution explored by the combined ab initio calculation and nonadiabatic dynamics simulation

In the present work, mechanism of the O₂(¹Δ_g) generation from the reaction of the dissolved Cl₂ with H₂O₂ in basic aqueous solution has been explored by the combined ab initio calculation and nonadiabatic dynamics simulation, together with different solvent models. Three possible pathways have been determined for the O₂(¹Δ_g) generation, but two of them are sequentially downhill processes until formation of the OOCl⁻ complex with water, which are of high exothermic character. Once the complex is formed, singlet molecular oxygen is easily generated by its decomposition along the singlet-state pathway. However, triplet molecular oxygen of O₂() can be produced with considerable probability through nonadiabatic intersystem crossing in the ¹Δ_g/ intersection region. It has been found that the coupled solvent, heavy-atom, and nonadiabatic effects have an important influence on the quantum yield of the O₂(¹Δ_g) generation. © 2018 Wiley Periodicals, Inc.     

Excitation-Wavelength-Dependent Functionalities of Temporally Controlled Sensing and Generation of Singlet Oxygen by a Photoexcited State Engineered Rhodamine 6G-Anthracene Conjugate

The present study provides design guidance for unique multipotent molecules that sense and generate singlet oxygen (¹O₂). A rhodamine 6G-aminomethylanthracene-linked donor-acceptor molecule ( RA ) is designed and synthesized for demonstrating wavelength-dependent functionalities as follows; (i) RA acts as a conventional fluorogenic ¹O₂ sensor molecule like the commercially available reagent, singlet oxygen sensor green (SOSG), when it absorbs ultraviolet (UV)-visible light and reacts with ¹O₂. (ii) RA acts as a temporally controlled ¹O₂ sensing reagent under the longer wavelength (∼700 nm) photosensitization. RA enters an intermediate state after capturing ¹O₂ and does not become strongly fluorescent until it is exposed to UV, blue, or green light. (iii) RA acts as an efficient photosensitizer to generate ¹O₂ under green light illumination. The spin-orbit charge transfer mediated intersystem crossing (SOCT-ISC) process achieves this function, and RA shows a potential cancer-killing effect on pancreatic cancer cells. The wavelength-switchable functionalities in RA offer to promise molecular tools to apply ¹O₂ in a spatiotemporal manner.     

Synthesis and thermal decomposition of hydrotrioxide obtained by ozonization of <Emphasis Type="Italic">exo</Emphasis>-bicyclo[2.2.1]heptan-2-ol

Low-temperature (−70 °C) ozonization of exo-bicyclo[2.2.1]heptan-2-ol in CCl₃F led to a hydrotrioxide, which was identified by ¹H NMR spectroscopy. Kinetics of decomposition of given hydrotrioxide was studied by analysis of the chemiluminescence fading in the IR range of the spectrum and the activation parameters of the process were calculated. Singlet oxygen (¹Δ_g) served as an emitter of eradiation. Yields of ¹O₂ in a range of temperature from −31.0 to +12.5 °C were determined (at −31 °C the yield was 37.6%). Bicyclo[2.2.1]heptan-2-one was found to be the main product of decomposition of the hydrotrioxide (the yield was 98%). Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 263–266, February, 2007.     

Oxidation of organic compounds by ozone on a surface

Adamantanol was obtained by the ozonization of adamantane, at -78 ° C, adsorbed on silica gel. Ozone does not decompose on silica gel in the absence of a substrate.Ozonization of adamantane on silica gel is accompanied by chemiluntinescence in the IR region. The chemiluminescence quenching is of first-order with the effective rate constantk'. In the range from 0.4 to 5 mmol, k' depends linearly on the amount of adamantane adsorbed on the silica gel. The activation energy E_a = 9.97±1.89 kcal mol^–1 and the pre-exponential factorA = (2.76±0.52) - 10⁶ were calculated from the temperature dependence ofk'.Translated from Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 375–378, February, 1996.     

Gadolinium(III) Porpholactones as Efficient and Robust Singlet Oxygen Photosensitizers

Construction of Gd^III photosensitizers is important for designing theranostic agents owing to the unique properties arising from seven unpaired f electrons of the Gd³⁺ ion. Combining these with the advantages of porpholactones with tunable NIR absorption, we herein report the synthesis of Gd^III complexes Gd‐1 – 4 ( 1 , porphyrin; 2 , porpholactone; 3 and 4 , cis‐ and trans‐porphodilactone, respectively) and investigated their function as singlet oxygen (¹O₂) photosensitizers. These Gd complexes displayed ¹O₂ quantum yields (Φ_Δs) from 0.64–0.99 with the order Gd‐1 < Gd‐2 < Gd‐3 < Gd‐4 . The gradually enhanced ¹O₂ sensitization after β‐oxazolone moiety replacement was ascribed to the narrowing of the energy gap (ΔE) between the lowest triplet states (T₁) of the ligand and the energy level of the ¹Δ_g→³Σ_g transition of ¹O₂. In particular, Gd‐4 is capable of excitation in the visible to NIR region (400–700 nm) with a quantum yield near unity. These Gd complexes were first demonstrated as efficient photosensitizers in photocatalysis such as oxidative C?H bond functionalization of secondary or tertiary amines, and the oxygenation of the natural product cholesterol. Finally, after glycosylation, these water‐soluble Gd complexes showed potential applications in photodynamic therapy (PDT) in HeLa cells. This work revealed that Gd^III complexes of “bioinspired” β‐modified porpholactones are efficient NIR photosensitizers and form a chemical basis to construct appealing photocatalysts and theranostic agents based on lanthanides.     

Switching the Mechanism of NADH Photooxidation by Supramolecular Interactions

A series of three Ru(II) polypyridine complexes was investigated for the selective photocatalytic oxidation of NAD(P)H to NAD(P)⁺ in water. A combination of (time-resolved) spectroscopic studies and photocatalysis experiments revealed that ligand design can be used to control the mechanism of the photooxidation: For prototypical Ru(II) complexes a ¹O₂ pathway was found. Rudppz ([(tbbpy)₂Ru(dppz)]Cl₂, tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine, dppz=dipyrido[3,2-a:2′,3′-c]phenazine), instead, initiated the cofactor oxidation by electron transfer from NAD(P)H enabled by supramolecular binding between substrate and catalyst. Expulsion of the photoproduct NAD(P)⁺ from the supramolecular binding site in Rudppz allowed very efficient turnover. Therefore, Rudppz permits repetitive selective assembly and oxidative conversion of reduced naturally occurring nicotinamides by recognizing the redox state of the cofactor under formation of H₂O₂ as additional product. This photocatalytic process can fuel discontinuous photobiocatalysis.     

Dimeric Sandwich‐like Ion Pairs in the Crystal Structure of Tetrabutylammonium Ozonide Ammoniate

The novel ionic ozonide {[N(C₄H₉)₄](O₃)}₄·4.75NH₃ was synthesized by ion‐exchange reaction in liquid ammonia. The crystal structure was determined by single crystal diffraction at 100 K (monoclinic space group P2₁, a = 15.014(11) Å, b = 13.696(10) Å, c = 19.890(15) Å, β = 105.407(12)°, V = 3943(5) ų, Z = 2). The structure consists of a packing of sandwich‐like dimeric ion pairs in which two ozonide anions are interspersed between two tetrabutylammonium cations. Ammonia molecules from the solvent are localized in cavities in the structure. They are involved in hydrogen bonding with the ozonide ions. The desolvated tetrabutylammonium ozonide forms stable solutions in dichloromethane which may open up novel possibilities of tapping into the synthetic potential of the ozonide ion.     

Chemiluminescence during decomposition of 1,4-dimethylnaphthalene endoperoxide on the silica gel and alumina surface

Decomposition of 1,4-dimethylnaphthalene endoperoxide supported on the silica gel and alumina surface is accompanied by chemiluminescence (CL) in the IR and visible spectral regions. The CL emitter in the IR region is singlet oxygen. The ¹O₂ dimol contributes mainly to the emission at λ_max = 630 and 700 nm. It was shown by the IR-CL method that endoperoxide decomposition on the sorbent surface follows the first-order kinetics. The activation parameters of the process were determined. On the Al₂O₃ and silica gel surfaces a substantial acceleration of the decomposition of 1,4-dimethylnaphthalene endoperoxide is observed compared to the solution. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 199–204, February, 2007.     

Kinetic model of a DC oxygen glow discharge

A simple kinetic model predicting the concentration of oxygen atoms, metastable singlet molecules O₂(a ¹) and negative ions O — in the positive column of a DC glow discharge is developed. The calculated O and O₂(a ¹) concentrations are compared to previously reported measurements for pressuresp=0.2–2 Torr and discharge currentsI=10–80 mA. The electron density calculated from the continuity equationj=n _e e v _d agrees well with experiment. The rate coefficients for electron impact processes used in the balance equations of O, O₂(a ¹), and O^– were taken from the literature as a function of the reduced electric fieldE/N forE/N=40–80 Td. A reasonable agreement is obtained between the model and the experiment with a set of 10 reactions for the production and destruction of the above-mentioned species     

Non-emissive RuII Polypyridyl Complexes as Efficient and Selective Photosensitizers for the Photooxidation of Benzylamines

Five new Ru^II polypyridyl complexes bearing N-(arylsulfonyl)-8-amidoquinolate ligands and three of their biscyclometalated Ir^III congeners have been prepared and employed as photocatalysts ( PC s) in the photooxidation of benzylamines with O₂. In particular, the new Ru^II complexes do not exhibit photoluminescence, rather they harvest visible light efficiently and are very stable in solution under irradiation with blue light. Their non-emissive behavior has been related to the low electrochemical energy gaps and rationalized on the basis of theoretical calculations (DFT analysis) that predict low S₀←T₁ energy values. Moreover, the Ru^II complexes, despite being non-emissive, display excellent activities in the selective photocatalytic transformation of benzylamines into the corresponding imines. The presence of an electron-withdrawing group (-CF3) on the arene ring of the N-(arylsulfonyl)-8-amidoquinolate ligand improves the photocatalytic activity of the corresponding photocatalyst. Furthermore, all the experimental evidence, including transient absorption spectroscopy measurements suggest that singlet oxygen is the actual oxidant. The Ir^III analogues are considerably more photosensitive and consequently less efficient photosensitizers ( PS s).     

Singlet oxygen quenching by Co(SacSac)2 complexes

Conclusion The quenching of the luminescence of¹O₂ by the Co (SasSac)₂ complex proceeds mainly by radiationless energy transfer to the low-lying electronic level of the quencher.Translated from Izvestiya Nauk SSSR, Seriya Khimicheskaya, No, 10, pp. 2361–2364, October, 1986.     

Involvement of Singlet Oxygen in the Solid‐State Photochemistry of P3HT

We studied the role that singlet oxygen plays in the solid‐state photochemistry of poly(3‐hexylthiophene) (P3HT). The photosensitized formation of singlet oxygen by solid‐state P3HT and its subsequent reactivity on the polymer were investigated. Using a fluorescent probe, it was found that singlet oxygen (¹O₂) could be produced by irradiation of P3HT by photosensitization, with no oxidation of the polymer. In addition, ¹O₂ was directly formed on P3HT via a chemical reaction, again with no oxidation of the polymer. These results give strong evidence that ¹O₂ is not the principal photo‐oxidative degradation intermediate of P3HT, which conflicts with previous reports.

     

Quenching of singlet oxygen by phenols

The rate constants for the quenching of singlet oxygen by sterically hindered phenols were determined. It was observed that the rate constant for the quenching increases with a decrease in the ionization potential of phenols.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2132–2134, December, 1993.This work was supported by the Russian Foundation for Basic Research (Grant 93-03-5231).     

Singlet oxygen‐induced protein aggregation: Lysozyme crosslink formation and nLC‐MS/MS characterization

Singlet molecular oxygen (¹O₂) has been associated with a number of physiological processes. Despite the recognized importance of ¹O₂‐mediated protein modifications, little is known about the role of this oxidant in crosslink formation and protein aggregation. Thus, using lysozyme as a model, the present study sought to investigate the involvement of ¹O₂ in crosslink formation. Lysozyme was photochemically oxidized in the presence of rose bengal or chemically oxidized using [¹⁸O]‐labeled ¹O₂ released from thermolabile endoperoxides. It was concluded that both ¹O₂ generating systems induce lysozyme crosslinking and aggregation. Using SDS‐PAGE and nano‐scale liquid chromatography coupled to electrospray ionization mass spectrometry, the results clearly demonstrated that ¹O₂ is directly involved in the formation of covalent crosslinks involving the amino acids histidine, lysine, and tryptophan.     

Metallophthalocyanine‐Based Conjugated Microporous Polymers as Highly Efficient Photosensitizers for Singlet Oxygen Generation

Singlet oxygen (¹O₂) is of great interest because of its potential applications in photodynamic therapy, photooxidation of toxic molecules, and photochemical synthesis. Herein, we report novel metallophthalocyanine (MPc) based conjugated microporous polymers (MPc‐CMPs) as photosensitizers for the generation of ¹O₂. The rigid microporous structure efficiently improves the exposure of the majority of the MPc units to oxygen. The MPc‐CMPs also exhibit an enhanced light‐harvesting capability in the far‐red region through their extended π‐conjugation systems. Their microporous structure and excellent absorption capability for long‐wavelength photons result in the MPc‐CMPs showing high efficiency for ¹O₂ generation upon irradiation with 700 nm light, as evident by using 1,3‐diphenylisobenzofuran as an ¹O₂ trap. These results indicate that MPc‐CMPs can be considered as promising photosensitizers for the generation of ¹O₂.     

Photochemical properties of carotenoids: what can we get from the VB model?

Photo-isomerization and anti-oxidation of carotenoids have been studied for many years be-cause of their diverse roles in photobiology, photochemistry and photomedicine[1—6]. The experi-mental works revealed that the changes in the geometry between S0 (the ground state) and T1 (the first triplet state) states are very important for the two processes. Meanwhile, theoretical studies have also been carried out to investigate these processes. The polyenes have usually been used as the models for…