В журнале Journal of Photochemistry and Photobiology B: Biology   (IF=4.383) опубликована статья  с участием сотрудников Института: к.х.н. И.А. Кирилюка (завлаб ЛАС) и д.ф.-м.н., проф. Е.Г. Багрянской (директор НИОХ, завлаб ЛМР)

Application of EPR to porphyrin-protein agents for photodynamic therapy

Natalya E.Sannikova, Ivan O. Timofeev, Alexey S. Chubarov, Natalya Sh. Lebedeva, Aleksandr S. Semeikin, Igor A. Kirilyuk, Yuri P. Tsentalovich, Matvey V. Fedin, Elena G. Bagryanskaya, Olesya A.Krumkacheva

Journal of Photochemistry and Photobiology B: Biology, 2020, V. 211, 112008

Abstract

Recently, a new type of spin labels based on photoexcited triplet molecules was proposed for nanometer scale distance measurements by pulsed dipolar electron paramagnetic resonance (PD EPR). However, such molecules are also actively used within biological complexes as photosensitizers for photodynamic therapy (PDT) of cancer. Up to date, the idea of using the photoexcited triplets simultaneously as PDT agents and as spin labels for PD EPR has never been employed. In this work, we demonstrate that PD EPR in conjunction with other methods provides valuable information on the structure and function of PDT candidate complexes, exemplified here with porphyrins bound to human serum albumin (HSA). Two distinct porphyrins with different properties were used: amphiphilic meso-tetrakis(4-hydroxyphenyl)porphyrin (mTHPP) and water soluble cationic meso-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4); HSA was singly nitroxide-labeled to provide a second tag for PD EPR measurements. We found that TMPyP4 locates in a cavity at the center of the four-helix bundle of HSA subdomain IB, close to the interface with solvent, thus being readily accessible to oxygen. As a result, the photolysis of the complex leads to photooxidation of HSA by generated singlet oxygen and causes structural perturbation of the protein. Contrary, in case of mTHPP porphyrin, the binding occurs at the proton-rich pocket of HSA subdomain IIIA, where the access of oxygen to a photosensitizer is hindered. Structural data of PD EPR were supported by other EPR techniques, laser flash photolysis and protein photocleavage studies. Therefore, pulsed EPR on complexes of proteins with photoexcited triplets is a promising approach for gaining structural and functional insights into such PDT agents.

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В журнале Applied Catalysis A: General   (IF=5.006) опубликована статья  с участием сотрудников Института: Е.С. Можайцева (мнс, ЛНТПС), к.х.н. Е.В. Суслова (зам.директора по науке, завлаб ЛНТПС), д.х.н., проф. РАН К.П. Волчо (гнс, ЛФАВ) и  чл.-корр. РАН, д.х.н., проф.  Н. Ф. Салахутдинова (рук. отдела ОМХ, завлаб ЛФАВ)

Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process

Yu.S.Demidova, E.S.Mozhaitsev, E.V.Suslov, A.A.Nefedov, A.A.Saraev, K.P.Volcho, N.F.Salakhutdinov, A.Simakov, I.L.Simakova, D.Yu.Murzine

Applied Catalysis A: General

Available online 21 August 2020, 
Volume 605, 5 September 2020, 117799

Abstract

In the current work gold nanoparticles supported on oxides (MgO, Al₂O₃, ZrO₂, TiO₂) were used for menthylamine synthesis via menthone oxime hydrogenation. An increase of the gold nanoparticles size and application of metal oxides with a strong basic character such as magnesia favored deoximation to menthone. Au/Al₂O₃ catalyst with the gold nanoparticles size of 2.0 nm afforded high catalytic activity and selectivity to menthylamine. The reaction kinetics including stereoselectivity to the reaction products and recyclability of the catalyst was studied using Au/Al₂O₃ in the temperature range 90-110 °C under hydrogen pressure of 5.5-7.5 bar. The catalytic behavior was influenced by the solvent nature, with higher selectivity to desired amine achieved using methanol. The reaction rate was pressure independent, while has first order with respect to menthone oxime concentration. Stereoselectivity to menthylamines and menthones was independent on the reaction temperature and the hydrogen pressure.

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В журнале European Journal of Medicinal Chemistry   (IF=5.572) опубликована статья  с участием сотрудников Института: к.х.н. А.С. Соколовой (снс, ЛФАВ), д.х.н.О.И. Яровой (внс, ЛФАВ), Е.Б. Мордвиновой (лаборантк, ЛФАВ), к.б.н. Д.С. Баева (снс, ЛФИ), д.б.н., проф. Т.Г. Толстиковой (завлаб ЛФИ) и  чл.-корр. РАН, д.х.н., проф.  Н. Ф. Салахутдинова (рук. отдела ОМХ, завлаб ЛФАВ)

Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process

European Journal of Medicinal Chemistry

Available online 20 August 2020,
Volume 207, 1 December 2020, 112726

Abstract

In this study, we screened a large library of (+)-camphor and (−)-borneol derivatives to assess their filovirus entry inhibition activities using pseudotype systems. Structure-activity relationship studies revealed several compounds exhibiting submicromolar IC₅₀ values. These compounds were evaluated for their effect against natural Ebola virus (EBOV) and Marburg virus. Compound 3b (As-358) exhibited the good antiviral potency (IC₅₀ = 3.7 μM, SI = 118) against Marburg virus, while the hydrochloride salt of this compound 3b·HCl had a strong inhibitory effect against Ebola virus (IC₅₀ = 9.1 μM, SI = 31) and good in vivo safety (LD₅₀ > 1000 mg/kg). The results of molecular docking and in vitro mutagenesis analyses suggest that the synthesized compounds bind to the active binding site of EBOV glycoprotein similar to the known inhibitor toremifene.

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В журнале Journal of Natural Products   (IF=3.779) опубликована статья  с участием сотрудников Института:  чл.-корр. РАН, д.х.н., проф.  Н. Ф. Салахутдинова (рук. отдела ОМХ, завлаб ЛФАВ),  д.х.н. О.И.  Лузиной (внс, ЛФАВ), А.С. Филимонова (мнс, ЛНТПС)

Usnic Acid Conjugates with Monoterpenoids as Potent Tyrosyl-DNA Phosphodiesterase 1 Inhibitors

J. Nat. Prod. 2020, 83,8,2320-2329
Publication Date:July 28, 2020

Abstract

Hybrid molecules created from different pharmacophores of natural and synthetic equivalents are successfully used in pharmaceutical practice. One promising target for anticancer therapy is tyrosyl-DNA phosphodiesterase 1 (Tdp1) because it can repair DNA lesions caused by DNA-topoisomerase 1 (Top1) inhibitors, resulting in drug resistance. In this study, new hybrid compounds were synthesized by combining the pharmacophoric moiety of a set of natural compounds with inhibitory properties against Tdp1, particularly, phenolic usnic acid and a set of different monoterpenoid fragments. These fragments were connected through a hydrazinothiazole linker. The inhibitory properties of the new compounds mainly depended on the structure of the terpenoid moieties. The two most potent compounds, 9a and 9b, were synthesized from citral and citronellal, which contain acyclic fragments with IC₅₀ values in the range of 10–16 nM. Some synthesized derivatives showed low cytotoxicity against HeLa cells and increased the effect of the Top1 inhibitor topotecan in vitro by three to seven times. These derivatives may be considered as potential agents for the development of anticancer therapies when combined with Top1 inhibitors.

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В  журнале Angewandte Chemie Int. Ed.   (IF=12.959) опубликована статья  с участием сотрудников Института:  д.х.н. Е. В. Третьякова(завлаб ЛИНИРР), к.х.н. С. И. Живетьевой (снс, ЛИНИРР),  д.х.н. И. Ю. Багрянской (внс, рук. ГРСА), к.х.н. М.С. Казанцева (завлаб, ЛОЭ), к.х.н. И.К. Шундриной (снс, ЛЭАСМ), к.х.н. Е.В. Зайцевой (нс, ЛМР), к.ф.-м.н. Д.А. Пархоменко (нс, ЛМР) и д.ф.-м.н., проф. Е.Г. Багрянской

Ferromagnetically Coupled S = 1 Chains in Crystals of Verdazyl‐Nitronyl Nitroxide Diradicals

Angewandte Chemie International Edition

Volume 59, Issue 46, November 9, 2020, Pages 20704-20710

Publication Date:July 27, 2020

Abstract

Thermally stable organic diradicals with a triplet ground state along with large singlet‐triplet energy gap have significant potential for advanced technological applications. A series of phenylene‐bridged diradicals with oxoverdazyl and nitronyl nitroxide units were synthesized via a palladium‐catalyzed cross‐coupling reaction of the corresponding iodoverdazyls with a nitronyl nitroxide‐2‐ide gold(I) complex with high yields (up to 82%). The synthesized diradicals exhibit high stability and do not decompose in an inert atmosphere up to 180 °C. The magnetic properties of prepared phenylene‐coupled diradicals were investigated and magneto‐structural correlations were established. For the studied diradicals, both substantial antiferromagnetic (D E ST » ‐64 cm –1 ) and ferromagnetic (D E ST ³ 25 and 100 cm –1 ) intramolecular exchange interactions were observed. The sign of the exchange interaction is determined both by the bridging moiety ( para ‐ or meta ‐phenylene) and by the type of oxoverdazyl block ( C ‐linked or N ‐linked). Upon crystallization, diradicals with the triplet ground state form unique one‐dimensional exchange‐coupled chains with strong intra‐ and weak inter‐diradical ferromagnetic coupling.

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В журнале International Journal of Molecular Sciences   (IF=4,556) опубликована статья  с участием сотрудников Института: чл.-корр. РАН, проф. д.х.н. Н.Ф. Салахутдинова (зав.отделом ЛФАВ), проф. РАН, д.х.н. К. П. Волчо (гнс, ЛФАВ),  к.х.н. Т. М. Хоменко (снс, ЛФАВ)

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

Int. J. Mol. Sci. 2020, 21(15), 5182
Publication Date:July 22, 2020

 (This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD) 2.0)

Abstract

Tyrosine phosphatase STEP (striatal-enriched tyrosine protein phosphatase) is a brain-specific protein phosphatase and is involved in the pathogenesis of many neurodegenerative diseases. Here, we examined the impact of STEP on the development of age-related macular degeneration (AMD)-like pathology in senescence-accelerated OXYS rats. Using OXYS and Wistar rats (control), we for the first time demonstrated age-dependent changes in Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the retina. The increases in STEP protein levels and the decrease of total and STEP phosphatase activities in the retina (as compared with Wistar rats) preceded the manifestation of clinical signs of AMD in OXYS rats (age 20 days). There were no differences in these retinal parameters between 13-month-old Wistar rats and OXYS rats with pronounced signs of AMD. Inhibition of STEP with TC-2153 during progressive AMD-like retinopathy (from 9 to 13 months of age) reduced the thickness of the retinal inner nuclear layer, as evidenced by a decreased amount of parvalbumin-positive amacrine neurons. Prolonged treatment with TC-2153 had no effect on Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the OXYS retina. Thus, TC-2153 may negatively affect the retina through mechanisms unrelated to STEP. View Full-Text

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В журнале The Journal of Physical Chemistry Letters   (IF=6,71) опубликована статья  с участием сотрудников Института к.х.н. О.И. Рогожниковой (с.н.с, ГИТР), Д.В. Трухина (снс, ГИТР),  к.х.н. А.А. Кужелева (нс, ЛОЭ), д.ф.-м.н., проф. Е.Г. Багрянской (Директор НИОХ), к.х.н. В.М. Тормышева (снс, рук. группы ГИТР)

Multiquantum Counting of Trityl Radicals

J. Phys. Chem. Lett. 2020, 11, 15, 6286–6290
Publication Date:July 15, 2020

Abstract

We demonstrate a series of multitrityl radical compounds where accurate spin-counting by pulsed electron paramagnetic resonance (EPR) can be achieved at X-band (9 GHz) frequencies, even for molecules with very short and flexible linkers. Multiquantum filter experiments, well-known from NMR, were used to count the number of coupled electron spins in these compounds. The six pulse double quantum filter sequence used in EPR for distance determinations in biradicals was used. Precise phase settings to separate higher quantum coherences were achieved by an arbitrary waveform generator. The trityl radicals have narrow spectral width so that homogeneous excitation of all spins by the pulses is possible. The transversal relaxation times of higher quantum coherences of trityl radicals are sufficiently long to allow their detection. Our results on model compounds show the potential of this approach to determine oligomeric states in protein complexes in their native environment using functionalized trityl spin labels.

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В  журнале Crystal Growth & Design   (IF=4,089) опубликована статья  с участием сотрудников Института к.х.н. Е.А. Чулановой н.с, ЛГеТС), Е.А. Радюш (мнс, ЛОЭ),  к.х.н. И.К. Шундриной (снс, ЛЭАСМ), д.х.н. И.Ю. Багрянской (внс, рук. группы ГРСА), к.х.н. Н.А. Семёнова (снс, ЛГеТС) и д.х.н. А.В. Зибарева (завлаб, ЛГеТС) 

Lewis Ambiphilicity of 1,2,5-Chalcogenadiazoles for Crystal Engineering: Complexes with Crown Ethers

Cryst. Growth Des. 2020, 20, 9, 5868–5879
Publication Date:July 13, 2020

Abstract

The cocrystallization of 1,2,5-chalcogenadiazoles (chalcogen E = S, Se, and Te) with cyclic polyethers 18-crown-6 (18-c-6) and dibenzo-18-crown-6 (db-18-c-6) yielded the molecular complexes characterized by X-ray diffraction and thermogravimetry/differential scanning calorimetry techniques together with density functional theory (DFT) calculations and quantum theory of atoms in molecule and natural bond orbitals analysis. The complexes are bound by multiple secondary bonding interactions, the most important of which reflects the Lewis ambiphilicity of 1,2,5-chalcogenadiazoles and includes charge transfer from O atoms of the ethers onto E atoms of the chalcogenadiazoles (i.e., chalcogen bonding), and the back-donation from E to O. For complexes of 18-c-6, the DFT-calculated energies of bonding interactions correlate with the melting temperatures of the complexes, as well as with the atomic number of E and the size of the E-associated σ-holes but not with the maximum of molecular electrostatic potential at the σ-holes. Taking into account the previous results, the Lewis ambiphilicity of 1,2,5-chalcogenadiazoles may be used for applications in crystal engineering.

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В журнале Applied Organometallic Chemistry   (IF=3,14) опубликована статья  с участием сотрудников Института д.х.н. И.И. Олейника (в.н.с, ЛЭАСМ) и  к.х.н. И.В. Олейник (с.н.с, ЛЭАСМ) 

Achieving strictly linear polyethylenes by the NNN‐Fe precatalysts finely tuned with different sizes of ortho‐cycloalkyl substituents

Applied Organometallic Chemistry 
Volume34, Issue11, November 2020, e5937

Abstract

Six examples of newly synthesized α,α’‐bis (aryl)‐2,3:5,6‐bis (pentame thylene)pyridyliron complexes [2,3:5,6‐{C₄H₈C(NAr)}₂C₅HN]FeCl₂ (Ar = 2‐(c‐C₅H₉)‐6‐MeC₆H₃ Fe1 , 2‐(c‐C₆H₁₁)‐6‐MeC₆H₃ Fe2 , 2‐(c‐C₈H₁₅)‐6‐MeC₆H₃ Fe3 , 2‐(c‐C₅H₉)‐4,6‐Me₂C₆H₂ Fe4 , 2‐(c‐C₆H₁₁)‐4,6‐Me₂C₆H₂ Fe5 , 2‐(c‐C₈H₁₅)‐4,6‐Me₂C₆H₂ Fe6 ; c refers as cyclic), on activation with methylalumoxane (MAO) or modified MAO (MMAO), exhibit high activities towards ethylene polymerization, producing strictly linear polyethylenes with terminal vinyl groups. The catalytic performances are systematically investigated along with various polymerization parameters as well as the microstructures of resultant polyethylenes. The steric hindrances of ortho‐cycloalkyl substituents of N_imino‐aryl groups significantly affect the activities of the corresponding iron precatalysts as well as the microstructures of resultant polyethylenes: higher steric hindrance the ortho‐cycloalkyl substituents, higher activity the iron precatalyst, lower molecular weight the resultant polyethylenes. Experimental observations are additionally supported by the computational study. The resultant polyethylenes exhibited excellent hydrophobicity.

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Funding Information

• Bureau of International Cooperation of Chinese Academy of Sciences. Grant Numbers: 121111KYSB20190005, No. 121111KYSB20190005
• Russian Foundation for Basic Research. Grant Numbers: 18‐53‐80031, No. 18‐53‐80031
• Russian State funded budget project. Grant Numbers: 0302‐2019‐0007, No. 0302‐2019‐0007
• National Natural Science Foundation of China. Grant Number: No. 21871275 and 51861145303

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В журнале Polymers   (IF=3,426) опубликован обзор  с участием  д.х.н., проф. Е.Г. Багрянской

Gérard Audran , Elena G. Bagryanskaya , Sylvain R. A. Marque and Pavel Postnikov

Polymers, 2020, 12 (7), 1481;

https://doi.org/10.3390/polym12071481

 

Abstract

Nitroxide-mediated polymerization is now a mature technique, at 35 years of age. During this time, several variants have been developed: electron spin capture polymerization (ESCP), photoNMP (NMP2), chemically initiated NMP (CI-NMP), spin label NMP (SL-NMP), and plasmon-initiated NMP (PI-NMP). This mini-review is devoted to the features and applications of these variants. 
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Keywords: nitroxide mediated polymerization; CI-NMP; SLNMP; PI-NMP; NMP2; ESCP

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New Variants of Nitroxide Mediated Polymerization   

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В журналк Dyes and Pigments (IF 4,018) опубликована статья с участием сотрудников
Института: к.х.н. А.Д. Куимова (мнс, ЛОЭ), к.х.н. К.С. Беккер (снс, ЛОЭ), И.Р. Коскина (мнс ЛОЭ), А.С. Сониной (нс, ЛОЭ), к.х.н. И.К. Шундриной (снс, ЛЭАСМ), к.х.н. М.С. Казанцева (зав.лаб, с.н.с ЛОЭ)

2-((9H-fluoren-9-ylidene)methyl)pyridine as a new functional block for aggregation induced emissive and stimuli-responsive materials

Abstract

Highly-emissive mechanofluorochromic (MFC) organic solids changing their emission colors upon exposure to mechanical stimuli are highly demanded for various practical applications. In this work we introduced a planarizable by intramolecular N⋯H bond 2-((9H-fluoren-9-ylidene)methyl)pyridine fragment featuring an Aggregation-Induced Emission Enhancement and, particularly, MFC property for its bithiophene derivative. A two compounds, 2-((9H-fluoren-9-ylidene)methyl)-5-(5-phenylthiophen-2-yl)pyridine (FTP) and 2-((9H-fluoren-9-ylidene)methyl)-5-([2,2′-bithiophen]-5-yl)pyridine (FTT) were synthesized and fully characterized. In liquid solution both compounds are low emissive, however in the solid state they exhibit the photoluminescence quantum yield of 33% and 13% for FTP and FTT, respectively. Remarkably, the powder of FTT demonstrates a self-reversible mechanofluorochromism: the emission spectrum red-shifts after the grinding or pressurization and it recovers during one-day of storage without any treatment. The powder X-ray diffraction and differential scanning calorimetry revealed the reversible phase transition under temperature and mechanic stimuli. Analysis of molecular structure shows that in the gas phase FTT has a planar geometry while in the solid state it loses the flatness due to the crystal environment. Our results speak in favor of the increase of FTT planarity under the pressure to be responsible for the observed mechanofluorochromism.

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В журнале Chemistry - A European Journal   (IF=5,16) опубликована статья  с участием сотрудника Института к.х.н. А.М. Агафонцева (с.н.с, ЛТС)

Ratiometric detection of ATP by fluorescent cyclophanes with bellows‐type sensing mechanism

Aleksandr M. Agafontsev, Tatiana A. Shumilova, Aleksandr S. Oshchepkov, Frank Hampel, Evgeny A Kataev

Chemistry - A European Journal, 

Volume 26 , Issue 44 Special Issue: Young Chemists 2020

August 6, 2020, Pages 9991-9997

This article also appears in:

• Young Chemists 2020

Abstract

Pyrene‐based cyclophanes have been synthesized with the aim to realize a bellows‐type sensing mechanism for the ratiometric detection of nucleotide concentrations in a buffered aqueous solution. The sensing mechanism involves the encapsulation of a nucleobase between two pyrene rings, which affects the monomer‐excimer equilibrium of the receptor in the excited state. The nature of the spacer and its connection pattern to pyrene rings have been varied to achieve high selectivity for ATP. The 1,8‐substituted pyrene‐based cyclophane with the 2,2′‐diaminodiethylamine spacer demonstrates the best selectivity for ATP showing a 50‐fold increase in the monomer‐excimer emission ratio upon saturation with the nucleotide. The receptor can detect ATP within the biological concentrations range over a wide pH range. NMR and spectroscopic studies have revealed the importance of hydrogen bonding and stacking interactions for achieving a required receptor selectivity. The probe has been successfully applied for the real‐time monitoring of creatine kinase activity.

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