Synthesis, characterization and biological activities of mononuclear Co(III) complexes as potential bioreductively activated prodrugs.

Aiming to investigate the use of tridentate ligands to develop new bireductively activated prodrugs, two N(2)O-donor ligands (HL1: [(2-hydroxybenzyl)(2-(imidazol-2-yl)ethyl)]amine; and HL2: [(2-hydroxybenzyl)(2-(pyridil-2-yl)ethyl]amine) were used to synthesize new Co(III) complexes, 1 and 2. Both complexes were characterized by X-ray crystallography, mass spectrometry, electrochemistry, IR, UV-visible and (1)H NMR spectroscopies. Electrochemical data in methanol revealed that the Co(III)-->Co(II) reduction of 1 (-0.84V vs. normal hydrogen electrode - NHE) is more positive than 2 (-1.13V vs. NHE), while it was expected to be more negative due to better sigma-donor ability of imidazole ring in HL1, compared to pyridine in HL2. Considering that reduction processes on Co(III) center may involve the lowest unoccupied molecular orbital (LUMO), it might play an important role on the electronic properties of the complexes, and could explain the observed redox potentials. Then, geometry optimizations of 1 and 2 were performed using the density functional theory (DFT), and different group participation in their LUMO is demonstrated. Using Saccharomyces cerevisiae cells as eukaryotic model, it is shown that in situ generated reduced species, 1(red) and 2(red), have high capacity to inhibit cellular growth, with IC50 (0.50mM for both complexes) lower than cisplatin IC50 (0.6mM) at the same time of exposure. Regarding to their ability to promote S. cerevisiae cells death, after 24 h, cells became susceptible only when exposed to 1(red) and 2(red): (i) at concentrations higher than 0.5mM in a non-dose dependence, and (ii) in anaerobic metabolism. These data reveal the potential of 1 and 2 as bioreductively activated prodrugs, since their oxidized forms do not present expressive activities when compared to their reduced forms.

1,5-Bis(2-formyl-phen-oxy)-3-oxapenta-ne.

In the title mol-ecule, C(18)H(18)O(5), the two aromatic rings are connected by a flexible 3-oxapentane chain. The mol-ecule has a crystallographic twofold rotation axis (C(2)) passing through the central O atom. An intra-molecular C-H⋯O hydrogen bond is observed in the solid state.

Potassium trifluoro-[(Z)-3-methoxy-prop-1-en-yl]borate.

In the title salt, K(+)·C(4)H(7)BF(3)O(-), the K atom is surrounded by six anions making close contacts through seven F [K⋯F = 2.779 (1)-3.048 (1) Å] and two O [K⋯O = 2.953 (2) and 3.127 (2) Å] atoms in a trivacant fac-vIC-9 icosa-hedral coordination geometry.

cis-Bis{1-[(4-nitro-phen-yl)diazen-yl]-2-naphtholato}dipyridine-nickel(II).

In the title compound, [Ni(C(16)H(10)N(3)O(3))(2)(C(5)H(5)N)(2)], the Ni(II) cation is in a distorted octa-hedral NiN(4)O(2) coordination by two independent bidentate 1-[(4-nitro-phen-yl)diazen-yl]-2-naph-thol-ate anions and two pyridine ligands. C-H⋯O inter-actions between aromatic rings and the O atoms of the nitro substituents build up a two-dimensional supra-molecular arrangement parallel to (100).

Potassium trifluoro-[(Z)-3-(oxan-2-yl-oxy)prop-1-en-1-yl]borate monohydrate.

The title compound, K(+)·C(8)H(13)BF(3)O(2) (-)·H(2)O, which was obtained from the reaction of a modified form of Z-vinylic telluride via a transmetalation reaction with n-BuLi, crystallizes as K(+) and C(8)H(13)BF(3)O(2) (-) ions along with a water mol-ecule. The K(+) cation is surrounded by four anions, making close contacts with six F atoms at 2.659 (3)-2.906 (3) Šand with two O atoms at 2.806 (3) and 2.921 (3) Šin a distorted bicapped trigonal-prismatic geometry.