{Ru(CO)(x)}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo

Gabriella Tamasi; Antonello Merlino; Federica Scaletti; Petra Heffeter; Anton A. Legin; Michael A. Jakupec; Walter Berger; Luigi Messori; Bernhard K. Keppler; Renzo Cini

doi:10.1039/c6dt04295c

{Ru(CO)(x)}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo

Gabriella Tamasi (Corresponding author), Antonello Merlino, Federica Scaletti, Petra Heffeter, Anton A. Legin, Michael A. Jakupec, Walter Berger, Luigi Messori, Bernhard K. Keppler (Corresponding author), Renzo Cini

Department of Inorganic Chemistry

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

The reaction of [RuII2(CO) ₆Cl ₂], 1, with N ³-methylbenzimidazole (MBI) and 5,6-dimethylbenzimidazole (DMBI) afforded two new complexes with the general formula fac-[Ru ^II(CO) ₃Cl ₂L], L = MBI (2) or DMBI (4). Crystals of cis,trans-[Ru ^II(CO) ₂Cl ₂(N ³-MBI) ₂], 3, were also obtained from the mother liquor that produced 2. In the presence of water, the dissociation of Ru-N, Ru-Cl and Ru-CO bonds occurred as a function of time, water content and pH. Density functional theory structure simulations/optimizations were carried out at the Becke3LYP level of theory for evaluating the relative stability of possible conformers. ESI-MS studies revealed the ability of the complexes to link model proteins, such as lysozyme, bovine pancreatic ribonuclease and cytochrome c, with the partial release of the heteroaromatic base, chlorido and carbonyl ligands. X-ray diffraction studies on crystals grown from a solution of HEWL and 2 showed the partial removal of chloride and CO. Cytotoxicity tests yielded two-digit micromolar IC ₅₀ values in CH1/PA-1 and SW480 cancer cells. In contrast to CORM-3 and 2, a significantly reduced tumor growth was observed with 4 in the murine colon cancer CT-26 model in vivo.

Original language	English
Pages (from-to)	3025-3040
Number of pages	16
Journal	Dalton Transactions
Volume	46
Issue number	9
DOIs	https://doi.org/10.1039/c6dt04295c
Publication status	Published - 7 Mar 2017

Austrian Fields of Science 2012

104003 Inorganic chemistry

Keywords

MONOXIDE-RELEASING MOLECULE
EGG-WHITE LYSOZYME
METAL-BASED DRUGS
CARBON-MONOXIDE
SPECTROSCOPIC PROPERTIES
RUTHENIUM COMPLEXES
CYTOCHROME-C
PROTEINS
CRYSTAL
CELLS

UN SDGs

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

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10.1039/c6dt04295c

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@article{ba2fda08e18e4efcb70b0c3f946382ec,

title = "{Ru(CO)(x)}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo",

abstract = "The reaction of [RuII2(CO) 6Cl 2], 1, with N 3-methylbenzimidazole (MBI) and 5,6-dimethylbenzimidazole (DMBI) afforded two new complexes with the general formula fac-[Ru II(CO) 3Cl 2L], L = MBI (2) or DMBI (4). Crystals of cis,trans-[Ru II(CO) 2Cl 2(N 3-MBI) 2], 3, were also obtained from the mother liquor that produced 2. In the presence of water, the dissociation of Ru-N, Ru-Cl and Ru-CO bonds occurred as a function of time, water content and pH. Density functional theory structure simulations/optimizations were carried out at the Becke3LYP level of theory for evaluating the relative stability of possible conformers. ESI-MS studies revealed the ability of the complexes to link model proteins, such as lysozyme, bovine pancreatic ribonuclease and cytochrome c, with the partial release of the heteroaromatic base, chlorido and carbonyl ligands. X-ray diffraction studies on crystals grown from a solution of HEWL and 2 showed the partial removal of chloride and CO. Cytotoxicity tests yielded two-digit micromolar IC 50 values in CH1/PA-1 and SW480 cancer cells. In contrast to CORM-3 and 2, a significantly reduced tumor growth was observed with 4 in the murine colon cancer CT-26 model in vivo. ",

keywords = "MONOXIDE-RELEASING MOLECULE, EGG-WHITE LYSOZYME, METAL-BASED DRUGS, CARBON-MONOXIDE, SPECTROSCOPIC PROPERTIES, RUTHENIUM COMPLEXES, CYTOCHROME-C, PROTEINS, CRYSTAL, CELLS",

author = "Gabriella Tamasi and Antonello Merlino and Federica Scaletti and Petra Heffeter and Legin, {Anton A.} and Jakupec, {Michael A.} and Walter Berger and Luigi Messori and Keppler, {Bernhard K.} and Renzo Cini",

note = "Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2017",

month = mar,

day = "7",

doi = "10.1039/c6dt04295c",

language = "English",

volume = "46",

pages = "3025--3040",

journal = "Dalton Transactions",

issn = "1477-9226",

publisher = "ROYAL SOC CHEMISTRY",

number = "9",

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TY - JOUR

T1 - {Ru(CO)(x)}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo

AU - Tamasi, Gabriella

AU - Merlino, Antonello

AU - Scaletti, Federica

AU - Heffeter, Petra

AU - Legin, Anton A.

AU - Jakupec, Michael A.

AU - Berger, Walter

AU - Messori, Luigi

AU - Keppler, Bernhard K.

AU - Cini, Renzo

N1 - Publisher Copyright: © The Royal Society of Chemistry.

PY - 2017/3/7

Y1 - 2017/3/7

N2 - The reaction of [RuII2(CO) 6Cl 2], 1, with N 3-methylbenzimidazole (MBI) and 5,6-dimethylbenzimidazole (DMBI) afforded two new complexes with the general formula fac-[Ru II(CO) 3Cl 2L], L = MBI (2) or DMBI (4). Crystals of cis,trans-[Ru II(CO) 2Cl 2(N 3-MBI) 2], 3, were also obtained from the mother liquor that produced 2. In the presence of water, the dissociation of Ru-N, Ru-Cl and Ru-CO bonds occurred as a function of time, water content and pH. Density functional theory structure simulations/optimizations were carried out at the Becke3LYP level of theory for evaluating the relative stability of possible conformers. ESI-MS studies revealed the ability of the complexes to link model proteins, such as lysozyme, bovine pancreatic ribonuclease and cytochrome c, with the partial release of the heteroaromatic base, chlorido and carbonyl ligands. X-ray diffraction studies on crystals grown from a solution of HEWL and 2 showed the partial removal of chloride and CO. Cytotoxicity tests yielded two-digit micromolar IC 50 values in CH1/PA-1 and SW480 cancer cells. In contrast to CORM-3 and 2, a significantly reduced tumor growth was observed with 4 in the murine colon cancer CT-26 model in vivo.

AB - The reaction of [RuII2(CO) 6Cl 2], 1, with N 3-methylbenzimidazole (MBI) and 5,6-dimethylbenzimidazole (DMBI) afforded two new complexes with the general formula fac-[Ru II(CO) 3Cl 2L], L = MBI (2) or DMBI (4). Crystals of cis,trans-[Ru II(CO) 2Cl 2(N 3-MBI) 2], 3, were also obtained from the mother liquor that produced 2. In the presence of water, the dissociation of Ru-N, Ru-Cl and Ru-CO bonds occurred as a function of time, water content and pH. Density functional theory structure simulations/optimizations were carried out at the Becke3LYP level of theory for evaluating the relative stability of possible conformers. ESI-MS studies revealed the ability of the complexes to link model proteins, such as lysozyme, bovine pancreatic ribonuclease and cytochrome c, with the partial release of the heteroaromatic base, chlorido and carbonyl ligands. X-ray diffraction studies on crystals grown from a solution of HEWL and 2 showed the partial removal of chloride and CO. Cytotoxicity tests yielded two-digit micromolar IC 50 values in CH1/PA-1 and SW480 cancer cells. In contrast to CORM-3 and 2, a significantly reduced tumor growth was observed with 4 in the murine colon cancer CT-26 model in vivo.

KW - MONOXIDE-RELEASING MOLECULE

KW - EGG-WHITE LYSOZYME

KW - METAL-BASED DRUGS

KW - CARBON-MONOXIDE

KW - SPECTROSCOPIC PROPERTIES

KW - RUTHENIUM COMPLEXES

KW - CYTOCHROME-C

KW - PROTEINS

KW - CRYSTAL

KW - CELLS

UR - http://www.scopus.com/inward/record.url?scp=85014164946&partnerID=8YFLogxK

U2 - 10.1039/c6dt04295c

DO - 10.1039/c6dt04295c

M3 - Article

VL - 46

SP - 3025

EP - 3040

JO - Dalton Transactions

JF - Dalton Transactions

SN - 1477-9226

IS - 9

ER -

{Ru(CO)(x)}-Core complexes with benzimidazole ligands: synthesis, X-ray structure and evaluation of anticancer activity in vivo

Abstract

Austrian Fields of Science 2012

Keywords

UN SDGs

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