Photoinduced inhibition of DNA repair enzymes and the possible mechanism of photochemical transformations of the ruthenium nitrosyl complex [RuNO(β-Pic)(NO)OH]

Photoinduced inhibition of DNA repair enzymes and the possible mechanism of photochemical transformations of the ruthenium nitrosyl complex [RuNO(β-Pic)(NO)OH]

In this work we have demonstrated that the ruthenium nitrosyl complex [RuNO(β-Pic) 2 (NO 2 ) 2 OH] is suitable for investigation of the inactivation of DNA repair enzymes in vitro . Photoinduced inhibition of DNA glycosylases such as E. coli Endo III, plant NtROS1, mammalian mNEIL1 and hNEIL2 occurs...

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Published in:Metallomics Vol. 11; no. 12; pp. 1999 - 29
Main Authors: Mikhailov, Artem A, Khantakova, Darya V, Nichiporenko, Vladislav A, Glebov, Evgeni M, Grivin, Vjacheslav P, Plyusnin, Victor F, Yanshole, Vadim V, Petrova, Daria V, Kostin, Gennadiy A, Grin, Inga R
Format: Journal Article
Language:English
Published: England Royal Society of Chemistry 11-12-2019
Subjects:
Coordination compounds
Deactivation
Deoxyribonucleic acid
DNA
DNA repair
E coli
Enzymes
Inactivation
Irradiation
Mass spectrometry
Mass spectroscopy
Nitric oxide
Nitrogen dioxide
Photochemicals
Photolysis
Repair
Ruthenium
Ruthenium compounds
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Summary:In this work we have demonstrated that the ruthenium nitrosyl complex [RuNO(β-Pic) 2 (NO 2 ) 2 OH] is suitable for investigation of the inactivation of DNA repair enzymes in vitro . Photoinduced inhibition of DNA glycosylases such as E. coli Endo III, plant NtROS1, mammalian mNEIL1 and hNEIL2 occurs to an extent of ≥90% after irradiation with the ruthenium complex. The photophysical and photochemical processes of [RuNO(β-Pic) 2 (NO 2 ) 2 OH] were investigated using stationary and time-resolved spectroscopy, and mass spectrometry. A possible mechanism of the photo-processes was proposed from the combined spectroscopic study and DTF calculations, which reveal that the photolysis is multistage. The primary and secondary photolysis stages are the photo-induced cleavage of the Ru-NO bond with the formation of a free nitric oxide and Ru III complex followed by ligand exchange with solvent. For E. coli Endo III, covalent interaction with the photolysis product was confirmed by UV-vis and mass spectrometric methods. Inhibition of DNA repair enzymes by the ruthenium nitrosyl complex occurs only after light irradiation and is determined by the interactions between the enzyme and active photolysis products.
Bibliography:10.1039/c9mt00153k
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content type line 23
ISSN:1756-5901
1756-591X
DOI:10.1039/c9mt00153k