Ligand-Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

Wen-Ying Zhang; Hannah E Bridgewater; Samya Banerjee; Joan J Soldevila-Barreda; Guy J Clarkson; Huayun Shi; Cinzia Imberti; Peter J Sadler

doi:10.1002/ejic.201901055

Ligand-Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

Wen-Ying Zhang, Hannah E Bridgewater, Samya Banerjee, Joan J Soldevila-Barreda, Guy J Clarkson, Huayun Shi, Cinzia Imberti, Peter J Sadler

University of Warwick

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Abstract

We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [Cp ^XRh(C ^{^}N)Z] ^0/+, in which Cp ^X = Cp*, Cp ^ph, or Cp ^biph, C ^{^}N = benzo[h]quinoline, and Z = chloride or pyridine. Three X-ray crystal structures showing the expected “piano-stool” configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9-ethyl guanine or glutathione compared to their pyridine analogues. The 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl complex [Cp ^biphRh(benzo-[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD ⁺ and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [Cp ^biphRh(benzo[h]quinoline)py] ⁺ (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5-fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand-controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes.

Original language	English
Pages (from-to)	1052-1060
Number of pages	9
Journal	European Journal of Inorganic Chemistry
Volume	2020
Issue number	11-12
Early online date	20 Oct 2019
DOIs	https://doi.org/10.1002/ejic.201901055
Publication status	Published - 27 Mar 2020
Externally published	Yes

Bibliographical note

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Funder

Funding Information:
This research was supported by the EPSRC (grant no. EP/P030572/1), Chancellor's International PhD Scholarships from the University of Warwick (for W.‐Y. Z. and H. S.), an EPSRC and Mike Enfys Bagguley PhD studentship for H. E. B, a Royal Society‐SERB Newton International Fellowship (NF151429 for S. B.), and the Wellcome Trust (209173/Z/17/Z for C. I.).

Funding Information:
This research was supported by the EPSRC (grant no. EP/P030572/1), Chancellor's International PhD Scholarships from the University of Warwick (for W.-Y. Z. and H. S.), an EPSRC and Mike Enfys Bagguley PhD studentship for H. E. B, a Royal Society-SERB Newton International Fellowship (NF151429 for S. B.), and the Wellcome Trust (209173/Z/17/Z for C. I.).

Keywords

Antitumor agents
Cyclopentadienyl ligands
Cytotoxicity
Reactive oxygen species
Rhodium

ASJC Scopus subject areas

Inorganic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ejic.201901055Licence: CC BY

PublishedFinal published version, 2.14 MBLicence: CC BY

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title = "Ligand-Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes",

abstract = "We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [Cp XRh(C ^N)Z] 0/+, in which Cp X = Cp*, Cp ph, or Cp biph, C ^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X-ray crystal structures showing the expected “piano-stool” configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9-ethyl guanine or glutathione compared to their pyridine analogues. The 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl complex [Cp biphRh(benzo-[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD + and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [Cp biphRh(benzo[h]quinoline)py] + (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5-fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand-controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes. ",

keywords = "Antitumor agents, Cyclopentadienyl ligands, Cytotoxicity, Reactive oxygen species, Rhodium",

author = "Wen-Ying Zhang and Bridgewater, {Hannah E} and Samya Banerjee and Soldevila-Barreda, {Joan J} and Clarkson, {Guy J} and Huayun Shi and Cinzia Imberti and Sadler, {Peter J}",

note = "This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: {\textcopyright} 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

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T1 - Ligand-Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

AU - Zhang, Wen-Ying

AU - Bridgewater, Hannah E

AU - Banerjee, Samya

AU - Soldevila-Barreda, Joan J

AU - Clarkson, Guy J

AU - Shi, Huayun

AU - Imberti, Cinzia

AU - Sadler, Peter J

N1 - This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2020/3/27

Y1 - 2020/3/27

N2 - We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [Cp XRh(C ^N)Z] 0/+, in which Cp X = Cp*, Cp ph, or Cp biph, C ^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X-ray crystal structures showing the expected “piano-stool” configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9-ethyl guanine or glutathione compared to their pyridine analogues. The 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl complex [Cp biphRh(benzo-[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD + and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [Cp biphRh(benzo[h]quinoline)py] + (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5-fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand-controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes.

AB - We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [Cp XRh(C ^N)Z] 0/+, in which Cp X = Cp*, Cp ph, or Cp biph, C ^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X-ray crystal structures showing the expected “piano-stool” configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9-ethyl guanine or glutathione compared to their pyridine analogues. The 1-biphenyl-2,3,4,5-tetramethylcyclopentadienyl complex [Cp biphRh(benzo-[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD + and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [Cp biphRh(benzo[h]quinoline)py] + (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5-fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand-controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes.

KW - Antitumor agents

KW - Cyclopentadienyl ligands

KW - Cytotoxicity

KW - Reactive oxygen species

KW - Rhodium

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M3 - Article

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SN - 1434-1948

VL - 2020

SP - 1052

EP - 1060

JO - European Journal of Inorganic Chemistry

JF - European Journal of Inorganic Chemistry

IS - 11-12

ER -

Ligand-Controlled Reactivity and Cytotoxicity of Cyclometalated Rhodium(III) Complexes

Abstract

Bibliographical note

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Keywords

ASJC Scopus subject areas

UN SDGs

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