Abstract
Over the past few decades metals in medicine have played to play a significant role, especially
after the discovery of the anticancer properties of cisplatin. However, acquired and intrinsic
resistance, toxicity and a host of side-effects have encouraged the research for new metal
based anticancer agents. Organometallic complexes have proved to be successful anticancer
agents and several have commenced clinical trials. The aim of this study was to prepare and
characterize trinuclear platinum group organometallic complexes and investigate their in vitro
activity.
The first series of ester containing complexes were prepared. The ligands were generated by
the preparation of Schiff base ligands obtained from the condensation of 4-
aminophenylmethanol and either benzaldehyde, 2-pyridinecarboxaldehyde or
salicylaldehyde. Trimeric ester ligands were prepared from these monomeric ligands by
reaction with trimesoyl chloride. The trimeric ligands were used to prepare a new series of
trinuclear polyester organometallic complexes using the dimeric precursors, [Ru(η6-p-
PriC6H4Me)Cl2]2, [Rh(η5-C5Me5)Cl2]2 or [Ir(η5-C5Me5)Cl2]2. The Schiff base ligands act as
bidentate donors to each metal. All compounds were characterized using nuclear magnetic
resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy, elemental analysis
(EA) and electron impact (EI) or electrospray ionization (ESI) mass spectrometry. Model
mononuclear analogues were prepared and the molecular structures of selected compounds
were determined by single crystal X-ray diffraction analysis. The mono- and trimeric ligands
and the metal complexes were evaluated for inhibitory effects against the human ovarian
cancer cell lines A2780 (cisplatin-sensitive) and A2780cisR (cisplatin-resistant), and the model
human skin fibroblast cell line, KMST-6. Upon coordination of the metal center an increase in
the activity against the ovarian cancer cells is observed, compared to the free ligands. The
trinuclear complexes displayed the greatest antiproliferative activity and exhibited selectivity
over the non-tumorigenic skin cells.
The second series of new trinuclear and model mononuclear cationic monodentate Rh(III),
Ir(III) and Ru(II) complexes with alkylated 1,3,5-triaza-7-phosphaadamantane (PTA) moieties
were prepared. Monoalkylation of the PTA moiety was achieved by reaction with
1,3,5-tris-(bromomethyl)benzene for the trimeric ligand or benzylbromide for the monomeric
ligand. The trinuclear cationic complexes were prepared from the dimeric precursors,
[Ru(η6-p-PriC6H4Me)Cl2]2, [Rh(η5-C5Me5)Cl2]2 or [Ir(η5-C5Me5)Cl2]2, and characterized using
NMR and IR spectroscopy, HR-ESI-mass spectrometry and elemental analysis. The ligands
coordinate to the metals via the phosphorous of the PTA, and this was confirmed by
v | P a g e
appropriate shifts in the 31P NMR spectra. The cytotoxicities of all alkylated PTA compounds
were investigated against WHCO1 esophageal cancer cell. The monomeric and trimeric
ligands displayed no activity. The trinuclear Rh(III) and Ir(III) complexes were more active than
the mononuclear analogues. The Ir(III) mononuclear complex proved to be the most cytotoxic
and 1H NMR model studies demonstrated its DNA binding ability, while UV-Vis studies
demonstrated the ability of the iridium mononuclear complex to interact with the double helix
structure of Red Salmon testes DNA.
The third series consists of new water soluble Rh(III) and Ir(III) sulfonated complexes. The
trimeric ligand was prepared via a Schiff base condensation between tris-2-(aminoethyl)amine
and 5-sulfonatosalicylaldehyde. Anionic trinuclear complexes were prepared from the dimeric
precursors, [Ru(η6-p-PriC6H4Me)Cl2]2, [Rh(η5-C5Me5)Cl2]2 or [Ir(η5-C5Me5)Cl2]2. Rh(III) and Ir(III)
complexes were also prepared by displacement of the labile metal-chloro ligand by reaction
with pyridine, 4-methylpyridine, 4-phenylpyridine and 4-ferrocenylpyridine. The sulfonated
complexes were characterized using NMR and IR spectroscopy, HR-ESI-mass spectrometry
and elemental analysis. The cytotoxicities of all sulfonated compounds were investigated
against WHCO1 cancer cells and the metal complexes displayed promising activity, while the
ligands showed no activity. Several of the trinuclear complexes exhibited comparable activity
to that of cisplatin. 1H NMR model studies demonstrated the most active compound’s DNA
binding ability.
Burgoyne, A (2021). Development, Synthesis and Anticancer Evaluation of Trinuclear Platinum Group Metal Organometallic Complexes. Afribary. Retrieved from https://afribary.com/works/development-synthesis-and-anticancer-evaluation-of-trinuclear-platinum-group-metal-organometallic-complexes
Burgoyne, Andrew "Development, Synthesis and Anticancer Evaluation of Trinuclear Platinum Group Metal Organometallic Complexes" Afribary. Afribary, 25 Apr. 2021, https://afribary.com/works/development-synthesis-and-anticancer-evaluation-of-trinuclear-platinum-group-metal-organometallic-complexes. Accessed 23 Dec. 2024.
Burgoyne, Andrew . "Development, Synthesis and Anticancer Evaluation of Trinuclear Platinum Group Metal Organometallic Complexes". Afribary, Afribary, 25 Apr. 2021. Web. 23 Dec. 2024. < https://afribary.com/works/development-synthesis-and-anticancer-evaluation-of-trinuclear-platinum-group-metal-organometallic-complexes >.
Burgoyne, Andrew . "Development, Synthesis and Anticancer Evaluation of Trinuclear Platinum Group Metal Organometallic Complexes" Afribary (2021). Accessed December 23, 2024. https://afribary.com/works/development-synthesis-and-anticancer-evaluation-of-trinuclear-platinum-group-metal-organometallic-complexes