Study of the effect induced by the substituents on the ring-chain tautomerism of Schiff bases derived from norephedrine.

The solution behavior and the spectroscopic properties of the novel Schiff bases (1S,2R)-R(1)CH=NCH(Me)CH(OH)Ph [with R(1) = ferrocenyl-[Fc (2b)], 5- or 3-methylthienyl [hereafter referred to as 5-MeTf and 3-MeTf (2c and 2d), respectively]] are reported. NMR studies show the existence of a tautomeric equilibrium between these imine forms (2b-d) and 2-substituted 4-methyl-5-phenyloxazolidines. The comparison of the results reveals that the molar ratios imine/oxazolidines (K): (a) are solvent and temperature dependent, (b) are higher than that obtained for (1S,2R)-PhCH=NCH(Me)CH(OH)Ph (2e), (c) are strongly affected by the nature of the R(1) group, and (d) increase according to the sequence Ph < Fc < 5-MeTf < 3-MeTf. Density functional theory (DFT) calculations on the open forms (imines 2b-e) and on the diastereomers of the closed forms (2-substituted 4-methyl-5-phenyl oxazolidines) have also been carried out in order to rationalize the differences detected in the solution behavior of 2b-d and their analogue with R(1) = Ph (2e).

A novel cyclometallated Pt(II)-ferrocene complex induces nuclear FOXO3a localization and apoptosis and synergizes with cisplatin to inhibit lung cancer cell proliferation.

Cisplatin is a platinum-based compound that acts as an alkylating agent and is used to treat a variety of malignant tumors including lung cancer. As cisplatin has significant limitations in the clinic, alternative platinum compounds such as cycloplatinated complexes have been considered as attractive anti-tumor agents. Here, we report the antiproliferative activity of a novel diastereomerically pure cycloplatinated complex (Sp,1S,2R)-[Pt{(κ(2)-C,N)[(η(5)-C5H3)-CH[double bond, length as m-dash]N-CH(Me)-CH(OH)-C6H5]Fe(η(5)-C5H5)}Cl(DMSO)] 6a, against A549 non-small cell lung cancer. Mechanistic studies revealed that compound 6a induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a in U2OS and A549 cells, respectively. Accordingly, treatment of A549 cells with compound 6a activates the intrinsic caspase pathway and dramatically increases the percentage of apoptotic cells. Furthermore, 6a displays a synergistic antiproliferative effect when applied together with cisplatin. Compound 6a is also active in other cancer cell lines including NCI-H460 large cell lung cancer cells. Importantly, antiproliferative activity of the platinacycle 6a on the non-tumor and non-proliferating 3T3-L1 cell line is weaker than in all cancer cell lines tested.

Diastereomerically pure platinum(II) complexes as antitumoral agents.: The influence of the mode of binding {(N), (N,O)- or (C,N)}- of (1S,2R)[(η5-C5H5)Fe{(η5-C5H4)CHNCH(Me)CH(OH)C6H5}] and the arrangement of the auxiliary ligands.

The study of the reactivity of (1S,2R) [(η(5)-C(5)H(5))Fe{[(η(5)-C(5)H(4)) CHNCH(Me)CH(OH)C(6)H(5)}] (1a) with cis-[PtCl(2)(DMSO)(2)] under different experimental conditions has allowed to isolate and characterize three pairs of isomeric and diastereomerically pure platinum(II) complexes. Two of the pairs are the trans- and cis- isomers of (1S,2R)[Pt{(η(5)-C(5)H(5))Fe[(η(5)-C(5)H(4))CHNCH(Me)CH(OH)C(6)H(5)]}Cl(2)(DMSO)] [trans-(2a) and cis-(3a), respectively], and of (1S,2R) [Pt{(κ(2)-N,O)(η(5)-C(5)H(5))Fe[(η(5)-C(5)H(4))CHNCH(Me)CH(O)C(6)H(5)]}Cl(DMSO)], {trans-(Cl, N) in (4a)} or a cis-(Cl, N) {in (5a)}; while the third one is formed by platinacycles: [Pt{(κ(2)-C,N[(η(5)-C(5)H(3))]CHN-CH(Me)CH(OH)C(6)H(5)]Fe(η(5)-C(5)H(5))}Cl(DMSO)] with different planar chirality [S(p) (in 6a) or R(p) (in 7a)]. The crystal structures of compounds 2a, 3a, 5a and 6a are also reported. The cytotoxic assessment of 1a-7a on lung (A549), breast (MDA-MB-231) and colon (HCT-116) cancer cell lines is also reported and reveals that the potency of the complexes is strongly dependent on the mode of binding of the iminoalcohol {(N) in 2a and 3a, (N,O)(-) in 4a and 5a or (C,N)(-) in 6a and 7a}, the relative arrangement of the monodentate ligands (in 2a-5a), and the planar chirality of the 1,2-ferrocenylunit in (6a and 7a). Among the new products (2a-7a), compounds 4a and 5a exhibit the highest potency with IC(50) values smaller than cisplatin in the three cancer cell lines assayed. Electrophoretic DNA migration studies in the presence of 2a-7a have been performed in order to get further insights into their mechanism of action. A comparative study of the solution behaviour of all the complexes in DMSO-d(6) or in DMSO-d(6):D(2)O (1:1) mixtures at 298 K is also reported.

Calibrating the coordination chemistry tool chest: metrics of bi- and tridentate ligands.

Bi- and multidentate ligands form part of the tools commonly used for designing coordination and supramolecular complexes with desired stereochemistries. Parameters and concepts usually employed include the normalized bite of bidentate ligands, their cis- or trans-coordinating ability, their rigidity or flexibility, or the duality of some ligands that can act in chelating or dinucleating modes. In this contribution we present a structural database study of over one hundred bi- and tridentate ligands that allows us to parametrize their coordinating properties and discuss the relevance of such parameters for the choice of coordination polyhedron or coordination sites.