Synthesis and antiproliferative activity of the heterobimetallic complexes [RuClCp(PPh3)-μ-dmoPTA-1κP:2κ2N,N′-MCl2] (M = Co, Ni, Zn; dmoPTA = 3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)

Abstract

The synthesis and characterization of three novel heterobimetallic derivatives of general formula [RuClCp(PPh₃)-μ-dmoPTA-1κP:2κ²N,N'-MCl₂] (M = Co (1), Ni (2) and Zn (3), dmoPTA = 3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) are described. The sizes of their diffusing units are in agreement with the solid-state structures of 2 and 3, supporting a similar solid-state structure for complex 1. The diamagnetic ruthenium-zinc derivative 3 was fully characterized in solution at 193 K by NMR. Electrochemical properties of the complexes were investigated by cyclic voltammetry, supporting the influence of the {MCl₂} moiety on the electronic properties of the Ru-unit. For the three complexes the GI₅₀ values were in the range 0.8-6.5 μM and comparable to those of the standard anticancer drug cis-platin in the same cell lines.

New Findings in Metal Complexes with Antiproliferative Activity Containing 1,3,5‐Triaza‐7‐phosphaadamantane (PTA) and Derivative Ligands

“…[46][47] These complexes showed similar properties than those with acac, [45] particularly the ruthenium atom of the {RuCpCl(dmoPTA)(PPh 3 )}-moiety was found to have a clear sensitiveness to the metal bonded to N CH3 but also to the ligands bonded to this metal. [46][47] These complexes showed similar properties than those with acac, [45] particularly the ruthenium atom of the {RuCpCl(dmoPTA)(PPh 3 )}-moiety was found to have a clear sensitiveness to the metal bonded to N CH3 but also to the ligands bonded to this metal.…”

“…of Me(CF 3 nonane (HdmoPTA) when the dmoPTA was reacted with KOH in EtOH. The proton between both N CH3 atoms in 55 can be removed easily using a 0.01 M KOH water solution or tBuOK in MeOH at room temperature, which gives the option to the ligand to [45][46][47][48][49] coordinate a second metal through the N CH3 atoms. Nevertheless, in presence of protic solvents such as EtOH, MeOH or H 2 O, the ligand dmPTA suffers the elimination of the CH 2 group between the N CH3 atoms giving rise to the new HdmoPTA, which can be isolated as tetrafluoroborate salt by reaction with HBF 4 .…”

“…[44,45] The ligand dmPTA is soluble in water and organic solvents such as acetonitrile, acetone, etc., and it is stable enough in non protic solvents. The reaction of 55 with tBuOK and M(acac) 2 [45][46][47] Interestingly, the redox properties of these Ru-complexes (Table 1) depend on the metal bonded to the atoms N CH3 , which could be a consequence of steric hindrance but mainly due to electronic effects. This ligand can be easily deprotonated and the resulting neutral phosphaneamine 3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (dmoPTA) is able to coordinate metals by the soft P but also through the two hard N CH3 atoms, behaving in the latter case as a chelate (Scheme 8).…”

“…The reaction of dmPTA(CF 3 SO 3 ) 2 with [RuClCp(PPh 3 ) 2 ] in refluxing acetone/MeOH/water, gives the yellow complex [RuClCp(1κP-HdmoPTA)(PPh 3 )](OSO 2 CF 3 ) (55), which was the first component of the so-called 1 st generation of complexes containing the ligand dmoPTA (Scheme 9) [45][46][47]. b) Formation of dmoPTA from dmPTA; c) acid/base equilibrium dmoPTA/HdmoPTA.…”

Evaluation of catalytic activity of [RuClCp(dmoPTA)(PPh3)](OSO2CF3) in the isomerization of allylic alcohols in water (dmoPTA=3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)

“…The catalytic activity of complexes 1 [10] 2-4 [11] (vide supra, Scheme 2) was assessed initially for the isomerisation of 1-octen-3-ol in H 2 O at 70 ºC both under Ar and air atmosphere. The isomerization of 1-octen-3-ol usually is the standard reaction to check the possible catalytic properties of a metal complex for isomerization of allylic alcohols [12].…”