Synthesis, electrochemical studies, density functional analysis and X-ray structures of trans,cis,cis-[RuCl2(N-methylimidazole)2(SbPh3)2] and trans,cis,cis-[RuCl2(4-methyl pyrimidine)2(SbPh3)2]. The role of C-H…N and C-H...Cl interactions in pyrimidine pairings and in tuning the angular approach of imidazole residues to metals

The reaction of trans-[RuCl2(SbPh3)4] (1) (Ph=C6H5) (Inorg. Chim. Acta 208 (1993) 189) with tenfold excess N-methylimidazole (Meim) and 4-methylpyrimidine (Mepym) in chloroform at reflux under ultrapure nitrogen produced trans,cis,cis-[RuCl2(Meim)2(SbPh3) 2] (2), and trans,cis,cis-[RuCl2(Mepym)2(SbPh3) 2] (3), respectively. The compounds were purified and crystallized from ethylacetate and absolute ethanol and gave single crystals of 2·C H3COOCH2CH3 and 3, respectively. The X-ray diffraction analyses showed that for both 2 and 3 the ligand substitutions on 1, takes place in cis-positions. The relative orientation of the two Meim and Mepym ligands around the Ru-N vectors is head-to-head and head-to-tail for 2 and 3, respectively, in the solid state, whereas free rotation was detected in solution (CDCl3) at 25°C. The Ru-N bond distances average 2.108(4) Å, 2, and 2.131(5) Å, 3, and are elongated by the trans influence and by the steric hindrance from the two SbPh3 ligands. Intramolecular attractive stacking interactions between one of the phenyl rings and one of the Meim or Mepym ligands in 2 and 3, attenuate the repulsive steric hindrance within the coordination sphere. The Ru-N-C bond angles for 2 differ by 5.2° but have the opposite trend for the two Meim ligands. This fact agrees with a small energy barrier for the in plane swinging of the Meim ring with respect to the Ru-N line and is related to the C-H⋯Cl intramolecular interactions. Both the Mepym ligands of 3 have intermolecular interactions of the type C-H⋯N (N⋯C, 3.63(1) Å), the two "paired bases" not being coplanar (dihedral angle, 46.5(3)°). A density functional and ab initio optimization analysis at the Becke3LYP/6-31G** level and CCSD(T)/6-31G** level, carried out on the Pym molecule and on the Pym⋯Pym adduct, confirmed the feasibility of the C-H⋯N interaction at least for an environment that is not aqueous and allowed computation of a pairing energy of -11.657 and -13.887 kJ mol-1, respectively. Structure optimization analyses were also performed on the model molecules, trans-[RuCl2(SbH3)4] at the Becke3LYP/LANL2DZ (6-31G**, Cl, H) level, and head-to-head and head-to-tail trans,cis,cis-[RuCl2(Im)2(SbH3) 2], head-to-head and head-to-tail trans,trans,trans-[RuCl2(Im)2(SbH3) 2], head-to-tail trans,cis,cis and trans,trans,trans-[RuCl2(Im)2(PH3) 2] at the Becke3LYP/LANL2DZ level. The difference between the electronic energies relevant to the two couples of isomers head-to-head and head-to-tail trans,cis,cis-[RuCl2(Im)2(SbH3)2] and trans,trans,trans-[RuCl2(Im)2(SbH3) 2] is no larger than 2.7 kJ mol-1, showing that inter- and intramolecular weak forces play a significant role in discriminating the most stable isomer, at the solid state. A planar model molecule of the type [Ru(Im)]2+ was fully optimized at the Becke3LYP/LANL2DZ level. The computed Ru-N(1)-C(2) bond angle is 126.3° and the computed energy required to bend the angle in plane in the range 118.0-134.0° is less than 5.0 kJ mol-1. This confirms that weak interactions like C-H⋯Cl can reasonably cause significant changes at the level of the Ru-N-C bending in plane for metal-imidazole complexes. In dichloromethane solution complex 2 displays a chemically reversible Ru(II)/Ru(III) oxidation with formal electrode potentials of -0.27 V (versus the ferrocene/ferricinium couple), whereas 3, trans,trans,trans-[RuCl2(Mepym)2(PPh3) 2] (5) and trans,trans,trans-[RuCl2(Thz)2(PPh3) 2] (6) (Thz, 1,3-thiazole) undergo the same type of oxidation process with electrode potential values +0.08, +0.07 and -0.06 V, respectively. Therefore, 2 looks like the more suitable for protein binding (after oxidation to the mono-cation), when compared to 3, 5, and 6, a step believed to be important for decreasing the toxicity of ruthenium based anticancer drugs.