Synthesis, Structure, and Selective Cytotoxicity of Organometallic Cp*RuII O-Alkyl-N-phenylcarbamate Sandwich Complexes

Abstract

Tetraphenylborate salts of the η 6 -arene Cp * Ru II O-alkyl-N-phenyl carbamate organometallic sandwich complexes, [Cp * Ru(PhNHCO 2 R)]BPh 4 for R = Me (1), Et (2), and n-Pr (3), have been prepared by a facile one-pot reaction between ruthenium trichloride, pentamethylcyclopentadiene, and phenylisocyanate in refluxing alcohol solutions, and have been characterized by Fourier-transform IR and NMR spectroscopy, electrospray mass spectrometry, and single-crystal X-ray structure determinations. In vitro cytotoxicity studies show the complexes to be potent growth inhibitors for a range of tumour cell lines, while expressing significantly lower levels of toxicity towards a normal human fibroblast cell line.

Nucleophilic substitution reactions of [(η5-Cp*)Ru(η6-C6H5CO2H)]+: Synthesis, characterization and cytotoxicity of organoruthenium ester and amide complexes

“…This effect is due to the electronwithdrawing nature of the [(h 5 -Cp*)Ru] þ fragment. In this way the [(h 5 -Cp*)Ru] þ group has been shown previously to catalyze the conversion of aromatic carboxylic acids in ethanol to ethyl esters [8,32], benzaldehydes in methanol to benzaldehyde dimethyl acetals [27], aromatic isocyanates to carbamates [20], and aromatic chlorides to fluorides [33]. During the present study the carbonyl carbon electrophile of complex (1) was found to be a versatile starting material for a range of nucleophilic substitution reactions involving nucleophiles such as alcohols, primary and secondary amines and aromatic sulfonamides.…”

Selective, Cytotoxic Organoruthenium(II) Full‐Sandwich Complexes: A Structural, Computational and In Vitro Biological Study

“…The promising antitumor effects displayed by these cationic organoruthenium molecules prompted us to synthesize and biologically evaluate structurally diverse libraries of ruthenium(II)-based full-sandwich complexes (Figure 1; in which R represents a series of substituted functional groups including carboxylic acids, acid fluorides, esters, thioesters, ketones, alcohols, carbamates, amides, sulphonamides, and glycoconjugates. [9] The results of these studies demonstrated the cationic organoruthenium complexes to possess potent and selective antiproliferative activity towards a range of cancerous cell lines in vitro, including human skin carcinoma (MM96L) and two individual phenotypes of breast cancer (MCF7 and MDA-MB-231), with the degree of growth inhibition dependent on the size and lipophilicity of the arene ligand. [9] Of particular interest, however, was the relative inactivity of the neutral ruthenocenyl complexes when compared to their corresponding cationic derivatives.…”

“…[9] The results of these studies demonstrated the cationic organoruthenium complexes to possess potent and selective antiproliferative activity towards a range of cancerous cell lines in vitro, including human skin carcinoma (MM96L) and two individual phenotypes of breast cancer (MCF7 and MDA-MB-231), with the degree of growth inhibition dependent on the size and lipophilicity of the arene ligand. [9] Of particular interest, however, was the relative inactivity of the neutral ruthenocenyl complexes when compared to their corresponding cationic derivatives. These mono-, 1,1'-di-, and pentasubstituted ruthenocenyl molecules were on average over two orders of magnitude less active than the respective cationic complexes, highlighting a relationship between positive charge and cytotoxic activity.…”

“…These mono-, 1,1'-di-, and pentasubstituted ruthenocenyl molecules were on average over two orders of magnitude less active than the respective cationic complexes, highlighting a relationship between positive charge and cytotoxic activity. [9] This structural dependence on both lipophilicity and a cationic charge, in addition to the notable specificity displayed by these complexes towards cancerous cells, thus suggests that these highly stable organoruthenium molecules may be exerting their cytotoxic effect in a manner similar to that of biologically active delocalized lipophilic cations (DLCs). As the name suggests, DLCs are lipophilic compounds that carry a positive charge delocalized across the surface of their molecular structure.…”

“…[9] The identification and purity of these compounds was assured through comparison of experimentally attained characterization data with prior published literature values. Starting materials and solvents were obtained from a commercial supplier (Aldrich) and used as received.…”