With the aim of assessing whether ruthenium(II) compounds with meridional geometry might be utilized as potential antitumor agents, a series of new, water-soluble, monofunctional ruthenium(II) complexes of the general formula mer-[Ru(L3)(N-N)X][Y]n (where L3 = 2,2′:6′,2 ″-terpyridine (tpy) or 4 ′-chloro-2,2′:6′,2″-terpyridine (Cl-tpy), N-N = 1,2-diaminoethane (en), 1,2-diaminocyclohexane (dach), or 2,2′ -bipyridine (bpy); X = Cl or dmso-S; Y = Cl, PF6 , or CF3SO3 ; n = 1 or 2, depending on the nature of X) were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and for three of them, i.e., [Ru(Cl-tpy)(bpy)Cl][Cl] (3Cl), [Ru(Cl-tpy)(en)(dmso-S)][Y]2 [Y = PF6 (6PF6), CF3SO3 (6OTf )] and [Ru(Cl-tpy)(bpy)(dmso-S)][CF3SO3 ]2 (8OTf ), the X-ray structure was also determined. The new terpyridine complexes, with the exception of 8, are well soluble in water (>25 mg/mL). 1H and 31P NMR spectroscopy studies performed on the three selected complexes [Ru(Cl-tpy)(N-N)Cl]+ [N-N = en (1), dach (2), and bpy (3)] demonstrated that, after hydrolysis of the Cl ligand, they are capable of interacting with guanine derivatives [i.e., 9-methylguanine (9MeG) or guanosine-5 ′ -monophosphate (5′-GMP)] through N7, forming monofunctional adducts with rates and extents that depend strongly on the nature of N-N: 1 ≈ 2 ≫ 3. In addition, compound 1 shows high selectivity toward 5′ -GMP compared to adenosine-5′-monophosphate (5′ -AMP), in a competition experiment. Quantitative kinetic investigations on 1 and 2 were performed by means of UV/visible spectroscopy. Overall, the complexes with bidentate aliphatic diamines proved to be superior to those with bpy in terms of solubility and reactivity (i.e., release of Cl− and capability to bind guanine derivatives). Contrary to the chlorido compounds, the corresponding dmso derivatives proved to be inert (viz., they do not release the monodentate ligand) in aqueous media.

New Water-Soluble Ruthenium(II) Terpyridine Complexes for Anticancer Activity: Synthesis, Characterization, Activation Kinetics, and Interaction with Guanine Derivatives

ZANGRANDO, ENNIO;ALESSIO, ENZO
2014

Abstract

With the aim of assessing whether ruthenium(II) compounds with meridional geometry might be utilized as potential antitumor agents, a series of new, water-soluble, monofunctional ruthenium(II) complexes of the general formula mer-[Ru(L3)(N-N)X][Y]n (where L3 = 2,2′:6′,2 ″-terpyridine (tpy) or 4 ′-chloro-2,2′:6′,2″-terpyridine (Cl-tpy), N-N = 1,2-diaminoethane (en), 1,2-diaminocyclohexane (dach), or 2,2′ -bipyridine (bpy); X = Cl or dmso-S; Y = Cl, PF6 , or CF3SO3 ; n = 1 or 2, depending on the nature of X) were synthesized. All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), and for three of them, i.e., [Ru(Cl-tpy)(bpy)Cl][Cl] (3Cl), [Ru(Cl-tpy)(en)(dmso-S)][Y]2 [Y = PF6 (6PF6), CF3SO3 (6OTf )] and [Ru(Cl-tpy)(bpy)(dmso-S)][CF3SO3 ]2 (8OTf ), the X-ray structure was also determined. The new terpyridine complexes, with the exception of 8, are well soluble in water (>25 mg/mL). 1H and 31P NMR spectroscopy studies performed on the three selected complexes [Ru(Cl-tpy)(N-N)Cl]+ [N-N = en (1), dach (2), and bpy (3)] demonstrated that, after hydrolysis of the Cl ligand, they are capable of interacting with guanine derivatives [i.e., 9-methylguanine (9MeG) or guanosine-5 ′ -monophosphate (5′-GMP)] through N7, forming monofunctional adducts with rates and extents that depend strongly on the nature of N-N: 1 ≈ 2 ≫ 3. In addition, compound 1 shows high selectivity toward 5′ -GMP compared to adenosine-5′-monophosphate (5′ -AMP), in a competition experiment. Quantitative kinetic investigations on 1 and 2 were performed by means of UV/visible spectroscopy. Overall, the complexes with bidentate aliphatic diamines proved to be superior to those with bpy in terms of solubility and reactivity (i.e., release of Cl− and capability to bind guanine derivatives). Contrary to the chlorido compounds, the corresponding dmso derivatives proved to be inert (viz., they do not release the monodentate ligand) in aqueous media.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2787723
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