Fabio Edafe

Anticancer activity of tetracationic arene ruthenium metalla-cycles.

A series of cationic metalla-cycles of the general formulae [(η(6)-p-cym)(4)Ru(4)(OO∩OO)(2)(N∩N)(2)](4+) and [(η(6)-p-cym)(4)Ru(4)(NO∩NO)(2)(N∩N)(2)](4+) has been prepared from the dinuclear arene ruthenium precursors [(η(6)-p-cym)(2)Ru(2)(OO∩OO)(2)Cl(2)] (OO∩OO = oxalato, 1,4-benzoquinonato-2,5-diolato, 1,4-naphtoquinonato-5,8-diolato, 9,10-anthraquinonato-1,4-diolato, 5,12-tetraquinonato-6,11-diolato) and [(η(6)-p-cym)(2)Ru(2)(NO∩NO)(2)Cl(2)] (NO∩NO = oxamido, oxonico) by reaction with two different bidentate linkers (N∩N = 1,2-bis(4-pyridyl)ethylene, 1,2-bis(4-pyridyl)ethane) in the presence of silver triflate. All complexes were isolated as triflate salts and characterised by NMR, infrared, UV-visible, mass spectrometry and by elemental analysis. The cytotoxicities of the tetranuclear ruthenium complexes have been established using ovarian A2780 and A2780cisR cancer cell lines. All complexes exhibit moderate to excellent activity on both the cisplatin resistant and cisplatin sensitive cells, thus suggesting a mode of action different from cisplatin.

Conjugation of organoruthenium(II) 3-(1h-benzimidazol-2-yl)pyrazolo[3,4-b]pyridines and Indolo[3,2-d]benzazepines to recombinant human serum albumin: A strategy to enhance cytotoxicity in cancer cells

Following our strategy of coupling cyclin-dependent kinase (Cdk) inhibitors with organometallic moieties to improve their physicochemical properties and bioavailability, five organoruthenium complexes (1c–5c) of the general formula [RuCl(η6-arene)(L)]Cl have been synthesized in which the arene is 4-formylphenoxyacetyl-η6-benzylamide and L is a Cdk inhibitor [3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1–L3) and indolo[3,2-d]benzazepines (L4 and L5)]. All of the compounds were characterized by spectroscopic and analytical methods. Upon prolonged standing (2–3 months) at room temperature, the dimethyl sulfoxide (DMSO) solutions of 1c and 2c–HCl afforded residues, which after recrystallization from EtOH and EtOH/H2O, respectively, were shown by X-ray diffraction to be cis,cis-[RuIICl2(DMSO)2(L1)]·H2O and mer-[RuIICl(DMSO)3(L2–H)]·H2O. Compound 5c, with a coordinated amidine unit, undergoes E/Z isomerization in solution. The antiproliferative activities and effects on the cell cycle of the new compounds were evaluated. Complexes 1c–5c are moderately cytotoxic to cancer cells (CH1, SW480, A549, A2780, and A2780cisR cell lines). Therefore, in order to improve their antiproliferative effects, as well as their drug targeting and delivery to cancer cells, 1c–5c were conjugated to recombinant human serum albumin, potentially exploiting the so-called “enhanced permeability and retention” effect that results in the accumulation of macromolecules in tumors. Notably, a marked increase in cytotoxicity of the albumin conjugates was observed in all cases.

Luminescent Ruthenium Tripod Complexes: Properties in Solution and on Conductive Surfaces

Two luminescent ruthenium complexes containing tripod-type end groups linked through a rigid spacer to a phenanthroline derivative, able to confer an axial geometry to the complexes, are described. One of the compounds is functionalized with thioacetate groups in order to link the metal complex to metallic surfaces. The photophysical and electrochemical behavior of the complexes are studied in solution and on conductive substrates and, furthermore, self-assembled monolayers are investigated in a junction using gold and an indium gallium eutectic, as electrodes, and by time-resolved confocal microscopy. The results show that the complexes form very stable and well-ordered monolayers because of the tripod system, which can anchor the complex almost perpendicular to the surfaces.

Luminescent acetylthiol derivative tripodal osmium(II) and iridium(III) complexes: Spectroscopy in solution and on surfaces*

Luminescent Os(II) and Ir(III) complexes containing a tripodal-type structure terminalized with three thiol derivatives are described. The tripod is introduced through derivatization, with a rigid spacer, of a phenanthroline ligand coordinated to the metal ion, and the entire structure possesses axial geometry. The geometry of the complexes combined with the three anchoring sites, the thiol groups, allows the complexes to adopt an almost perpendicular arrangement to the surfaces and the formation of a well-packed monolayer on Au substrates. The photophysical and electrochemical behavior of the complexes is studied in solution and on surfaces. Furthermore, a self-assembled monolayer (SAM) of Os(II) complexes on an ultraflat Au surface is used to fabricate a metal–molecule–metal junction with Au and In Ga eutectic as electrodes. The Os(II) SAM in the tunneling junction exhibits rectification behavior which is opposite in direction to that which we have previously shown for Ru(II) SAMs.