The π-back-bonding modulation and its impact in the electronic properties of Cu(II) antineoplastic compounds: an experimental and theoretical study.

A complete study of the electronic density distribution in antineoplastic mixed chelate complexes of the type [Cu(N-N)(glycinate)H2 O]NO3 (N-N=2,2'-bipyridine (bpy) (1), 4,4'-dimethyl-bpy (2), 5,5'-dimethyl-2,2'-bipyridine (3), 1,10-phenanthroline (phen) (4), 4-methyl-phen (5); 5-methyl-phen (6); 4,7-dimethyl-phen (7), 5,6-dimethyl-phen (8), and 3,4,7,8-tetramethyl-phen (9)), a family known as Casiopeínas, was carried out with cyclic voltammetry, EPR, and computational methods. Crystal structures of 1⋅H2 O, 2⋅H2 O, 3⋅H2 O, 6⋅H2 O, and 8⋅H2 O show the variability in the geometries adopted by the copper compounds in the solid state. Experimental properties are described employing electronic descriptors obtained from computational methods. The main descriptors found were: The total electronic population of the metal ion (N(Cu)), delocalization of the metal ion electrons over the donor atoms (Δ(Cu)), atomic dipolar moment (μ(Cu)), and the atomic quadrupole moment (Q(Cu)). It was found that π-back-bonding is the principal factor that modulates the distribution of the electron density around the metal ion. The electronic descriptors obtained from the computational approach can be used as electronic descriptors of inorganic compounds that have shown antiproliferative activities instead the experimental data, aiding the rational design of good candidates of metal-based drugs.