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Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions

Targeted and enantioselective delivery of chiral diagnostic-probes and therapeutics into specific compartments inside cells is of utmost importance in the improvement of disease detection and treatment. The classical DNA ‘light-switch’ ruthenium(II)-polypyridyl complex, [Ru(DIP)(2)(dppz)]Cl(2) (DIP ...

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Autores principales: Chao, Xi-Juan, Huang, Chun-Hua, Tang, Miao, Yan, Zhu-Ying, Huang, Rong, Li, Yan, Zhu, Ben-Zhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123113/
https://www.ncbi.nlm.nih.gov/pubmed/36938880
http://dx.doi.org/10.1093/nar/gkad155
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author Chao, Xi-Juan
Huang, Chun-Hua
Tang, Miao
Yan, Zhu-Ying
Huang, Rong
Li, Yan
Zhu, Ben-Zhan
author_facet Chao, Xi-Juan
Huang, Chun-Hua
Tang, Miao
Yan, Zhu-Ying
Huang, Rong
Li, Yan
Zhu, Ben-Zhan
author_sort Chao, Xi-Juan
collection PubMed
description Targeted and enantioselective delivery of chiral diagnostic-probes and therapeutics into specific compartments inside cells is of utmost importance in the improvement of disease detection and treatment. The classical DNA ‘light-switch’ ruthenium(II)-polypyridyl complex, [Ru(DIP)(2)(dppz)]Cl(2) (DIP = 4,7-diphenyl-1,10-phenanthroline, dppz = dipyridophenazine) has been shown to be accumulated only in the cytoplasm and membrane, but excluded from its intended nuclear DNA target. In this study, the cationic [Ru(DIP)(2)(dppz)](2+) is found to be redirected into live-cell nucleus in the presence of lipophilic 3,5-dichlorophenolate or flufenamate counter-anions via ion-pairing mechanism, while maintaining its original DNA recognition characteristics. Interestingly and unexpectedly, further studies show that only the Δ-enantiomer is selectively translocated into nucleus while the Λ-enantiomer remains trapped in cytoplasm, which is found to be mainly due to their differential enantioselective binding affinities with cytoplasmic proteins and nuclear DNA. More importantly, only the nucleus-relocalized Δ-enantiomer can induce obvious DNA damage and cell apoptosis upon prolonged visible-light irradiation. Thus, the use of Δ-enantiomer can significantly reduce the dosage needed for maximal treatment effect. This represents the first report of enantioselective targeting and photosensitization of classical Ru(II) complex via simple ion-pairing with suitable weak acid counter-anions, which opens new opportunities for more effective enantioselective cancer treatment.
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spelling pubmed-101231132023-04-25 Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions Chao, Xi-Juan Huang, Chun-Hua Tang, Miao Yan, Zhu-Ying Huang, Rong Li, Yan Zhu, Ben-Zhan Nucleic Acids Res Chemical Biology and Nucleic Acid Chemistry Targeted and enantioselective delivery of chiral diagnostic-probes and therapeutics into specific compartments inside cells is of utmost importance in the improvement of disease detection and treatment. The classical DNA ‘light-switch’ ruthenium(II)-polypyridyl complex, [Ru(DIP)(2)(dppz)]Cl(2) (DIP = 4,7-diphenyl-1,10-phenanthroline, dppz = dipyridophenazine) has been shown to be accumulated only in the cytoplasm and membrane, but excluded from its intended nuclear DNA target. In this study, the cationic [Ru(DIP)(2)(dppz)](2+) is found to be redirected into live-cell nucleus in the presence of lipophilic 3,5-dichlorophenolate or flufenamate counter-anions via ion-pairing mechanism, while maintaining its original DNA recognition characteristics. Interestingly and unexpectedly, further studies show that only the Δ-enantiomer is selectively translocated into nucleus while the Λ-enantiomer remains trapped in cytoplasm, which is found to be mainly due to their differential enantioselective binding affinities with cytoplasmic proteins and nuclear DNA. More importantly, only the nucleus-relocalized Δ-enantiomer can induce obvious DNA damage and cell apoptosis upon prolonged visible-light irradiation. Thus, the use of Δ-enantiomer can significantly reduce the dosage needed for maximal treatment effect. This represents the first report of enantioselective targeting and photosensitization of classical Ru(II) complex via simple ion-pairing with suitable weak acid counter-anions, which opens new opportunities for more effective enantioselective cancer treatment. Oxford University Press 2023-03-20 /pmc/articles/PMC10123113/ /pubmed/36938880 http://dx.doi.org/10.1093/nar/gkad155 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Chemical Biology and Nucleic Acid Chemistry
Chao, Xi-Juan
Huang, Chun-Hua
Tang, Miao
Yan, Zhu-Ying
Huang, Rong
Li, Yan
Zhu, Ben-Zhan
Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions
title Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions
title_full Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions
title_fullStr Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions
title_full_unstemmed Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions
title_short Unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral Ru(II) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions
title_sort unusual enantioselective cytoplasm-to-nucleus translocation and photosensitization of the chiral ru(ii) cationic complex via simple ion-pairing with lipophilic weak acid counter-anions
topic Chemical Biology and Nucleic Acid Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123113/
https://www.ncbi.nlm.nih.gov/pubmed/36938880
http://dx.doi.org/10.1093/nar/gkad155
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