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Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril

The toxicity (IC(50)) of a series of mononuclear ruthenium complexes containing bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (bb(n)) as a tetradentate ligand against three eukaryotic cell lines—BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (li...

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Autores principales: Sun, Biyun, Musgrave, Ian F., Day, Anthony I., Heimann, Kirsten, Keene, F. Richard, Collins, J. Grant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287197/
https://www.ncbi.nlm.nih.gov/pubmed/30560120
http://dx.doi.org/10.3389/fchem.2018.00595
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author Sun, Biyun
Musgrave, Ian F.
Day, Anthony I.
Heimann, Kirsten
Keene, F. Richard
Collins, J. Grant
author_facet Sun, Biyun
Musgrave, Ian F.
Day, Anthony I.
Heimann, Kirsten
Keene, F. Richard
Collins, J. Grant
author_sort Sun, Biyun
collection PubMed
description The toxicity (IC(50)) of a series of mononuclear ruthenium complexes containing bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (bb(n)) as a tetradentate ligand against three eukaryotic cell lines—BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (liver carcinoma)—have been determined. The results demonstrate that cis-α-[Ru(Me(4)phen)(bb(7))](2+) (designated as α-Me(4)phen-bb(7), where Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline) showed little toxicity toward the three cell lines, and was considerably less toxic than cis-α-[Ru(phen)(bb(12))](2+) (α-phen-bb(12)) and the dinuclear complex [{Ru(phen)(2)}(2){μ-bb(12)}](4+). Fluorescence spectroscopy was used to study the binding of the ruthenium complexes with human serum albumin (HSA). The binding of α-Me(4)phen-bb(7) to the macrocyclic host molecule cucurbit[10]uril (Q[10]) was examined by NMR spectroscopy. Large upfield (1)H NMR chemical shift changes observed for the methylene protons in the bb(7) ligand upon addition of Q[10], coupled with the observation of several intermolecular ROEs in ROESY spectra, indicated that α-Me(4)phen-bb(7) bound Q[10] with the bb(7) methylene carbons within the cavity and the metal center positioned outside one of the portals. Simple molecular modeling confirmed the feasibility of the binding model. An α-Me(4)phen-bb(7)-Q[10] binding constant of 9.9 ± 0.2 × 10(6) M(−1) was determined by luminescence spectroscopy. Q[10]-encapsulation decreased the toxicity of α-Me(4)phen-bb(7) against the three eukaryotic cell lines and increased the binding affinity of the ruthenium complex for HSA. Confocal microscopy experiments indicated that the level of accumulation of α-Me(4)phen-7 in BHK cells is not significantly affected by Q[10]-encapsulation. Taken together, the combined results suggest that α-Me(4)phen-7 could be a good candidate as a new antimicrobial agent, and Q[10]-encapsulation could be a method to improve the pharmacokinetics of the ruthenium complex.
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spelling pubmed-62871972018-12-17 Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril Sun, Biyun Musgrave, Ian F. Day, Anthony I. Heimann, Kirsten Keene, F. Richard Collins, J. Grant Front Chem Chemistry The toxicity (IC(50)) of a series of mononuclear ruthenium complexes containing bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (bb(n)) as a tetradentate ligand against three eukaryotic cell lines—BHK (baby hamster kidney), Caco-2 (heterogeneous human epithelial colorectal adenocarcinoma) and Hep-G2 (liver carcinoma)—have been determined. The results demonstrate that cis-α-[Ru(Me(4)phen)(bb(7))](2+) (designated as α-Me(4)phen-bb(7), where Me(4)phen = 3,4,7,8-tetramethyl-1,10-phenanthroline) showed little toxicity toward the three cell lines, and was considerably less toxic than cis-α-[Ru(phen)(bb(12))](2+) (α-phen-bb(12)) and the dinuclear complex [{Ru(phen)(2)}(2){μ-bb(12)}](4+). Fluorescence spectroscopy was used to study the binding of the ruthenium complexes with human serum albumin (HSA). The binding of α-Me(4)phen-bb(7) to the macrocyclic host molecule cucurbit[10]uril (Q[10]) was examined by NMR spectroscopy. Large upfield (1)H NMR chemical shift changes observed for the methylene protons in the bb(7) ligand upon addition of Q[10], coupled with the observation of several intermolecular ROEs in ROESY spectra, indicated that α-Me(4)phen-bb(7) bound Q[10] with the bb(7) methylene carbons within the cavity and the metal center positioned outside one of the portals. Simple molecular modeling confirmed the feasibility of the binding model. An α-Me(4)phen-bb(7)-Q[10] binding constant of 9.9 ± 0.2 × 10(6) M(−1) was determined by luminescence spectroscopy. Q[10]-encapsulation decreased the toxicity of α-Me(4)phen-bb(7) against the three eukaryotic cell lines and increased the binding affinity of the ruthenium complex for HSA. Confocal microscopy experiments indicated that the level of accumulation of α-Me(4)phen-7 in BHK cells is not significantly affected by Q[10]-encapsulation. Taken together, the combined results suggest that α-Me(4)phen-7 could be a good candidate as a new antimicrobial agent, and Q[10]-encapsulation could be a method to improve the pharmacokinetics of the ruthenium complex. Frontiers Media S.A. 2018-11-30 /pmc/articles/PMC6287197/ /pubmed/30560120 http://dx.doi.org/10.3389/fchem.2018.00595 Text en Copyright © 2018 Sun, Musgrave, Day, Heimann, Keene and Collins. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Sun, Biyun
Musgrave, Ian F.
Day, Anthony I.
Heimann, Kirsten
Keene, F. Richard
Collins, J. Grant
Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril
title Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril
title_full Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril
title_fullStr Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril
title_full_unstemmed Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril
title_short Eukaryotic Cell Toxicity and HSA Binding of [Ru(Me(4)phen)(bb(7))](2+) and the Effect of Encapsulation in Cucurbit[10]uril
title_sort eukaryotic cell toxicity and hsa binding of [ru(me(4)phen)(bb(7))](2+) and the effect of encapsulation in cucurbit[10]uril
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287197/
https://www.ncbi.nlm.nih.gov/pubmed/30560120
http://dx.doi.org/10.3389/fchem.2018.00595
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