Novel multifunctional and multitarget homo- (Fe2) and heterobimetallic [(Fe,M) with M = Re or Mn] sulfonyl hydrazones.

The synthesis and characterization of the novel ferrocenyl sulfonyl hydrazide [Fe(η5-C5H5){(η5-C5H4)-S(O)2-NH-NH2}] (2) is reported. Additional studies on its reactivity using acetone or the ferrocenyl-, cyrhetrenyl- or cymantrenyl-aldehydes have allowed us to isolate and characterize [Fe(η5-C5H5){(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CMe2}] (3), the bis(ferrocenyl) derivative [Fe(η5-C5H5){[(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CH-(η5-C5H4)]Fe(η5-C5H5)}] (4) and the heterodimetallic compounds [Fe(η5-C5H5){[(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CH-(η5-C5H4)]M(CO)3}] with M = Re (5a) or Mn (5b). The X-ray crystal structures of compounds 3, 5a and 5b are also reported. A comparative study of their electrochemical and spectroscopic properties is also described. Additional computational calculations based on the DFT methodology have allowed us to elucidate the effect produced by the replacement of the terminal -NH2 (in 2) by the -N[double bond, length as m-dash]CMe2 (in 3) and -N[double bond, length as m-dash]CHR (in 4, 5a and 5b) moieties on the electronic distribution and to explain the differences detected in their electrochemical properties and absorption spectra. In vitro cytotoxicity studies of compounds 2, 4, 5a and 5b on the HCT-116 (colon), MCF7 and MDA-MB231 (breast) cancer cell lines reveal that compound 2 has no significant activity (IC50 > 100 µM), while its derivatives 4, 5a and 5b proved to be active in the three cancer cell lines selected in this study. The growth inhibition potency of compounds 5a and 5b against the triple negative MDA-MB231 breast cancer cell line is similar (or slightly) greater than that of cisplatin. Moreover, compounds 2, 4, 5a and 5b are less toxic than cisplatin in the normal and non-tumoral BJ fibroblasts, and the heterodimetallic complexes 5a and 5b with selective index >2.1 show an outstanding selective toxicity towards the MDA-MB231 cancer cells.

A novel type of organometallic 2-R-2,4-dihydro-1H-3,1-benzoxazine with R = [M(η5-C5H4)(CO)3] (M = Re or Mn) units. Experimental and computational studies of the effect of substituent R on ring-chain tautomerism.

The syntheses, characterization, X-ray crystal structures, electrochemical properties and anticancer and antichagasic activities of the first examples of 2-substituted 2,4-dihydro-1H-3,1-benzoxazines with half-sandwich organometallic arrays, [M(η5-C5H4)(CO)3] (M = Re or Mn), at position-2 are described. Experimental and computational studies based on DFT calculations on the open forms [Schiff bases of general formulae R-CH[double bond, length as m-dash]N-C6H4-2-CH2OH] (5), with R = ferrocenyl (a), phenyl (b), cyrhetrenyl (c) or cymantrenyl (d), and their tautomeric forms (2-substituted 2,4-dihydro-1H-3,1 benzoxazines) have allowed us to establish the influence of substituents a-d and solvents on: (a) the extent of tautomeric equilibria (5a-5d) ↔ (6a-6d) and (b) their electrochemical properties and the electronic distribution on the open and closed forms. Despite the formal similarity between 6c and 6d, their anticancer and antiparasitic activities are markedly different. Compound 6d is inactive in the HCT116, MDA-MB231 and MCF7 cancer cell lines, but 6c shows moderate activity in the latter cell line, while the Mn(i) complex (6d) is a more potent anti-Trypanosoma cruzi agent than its Re(i) analogue (6c).

Isomeric and hybrid ferrocenyl/cyrhetrenyl aldimines: a new family of multifunctional compounds.

The synthesis and characterization of two novel and isomeric hybrid ferrocenyl/cyrhetrenyl aldimines [(η5-C5H5)Fe{(η5-C5H4)-CH[double bond, length as m-dash]N-(η5-C5H4)}Re(CO)3] (1) and [(η5-C5H5)Fe{(η5-C5H4)-N[double bond, length as m-dash]CH-(η5-C5H4)}Re(CO)3] (2) are reported. Their X-ray crystal structures reveal that both adopt the E form. However, molecules of 1 and 2 differ in the relative arrangement of the "Fe(η5-C5H5)" and "Re(CO)3" units (anti in 1 and syn in 2). This affects the type of intermolecular interactions, the assembly of the molecules and therefore their crystal architecture. Comparative studies of their electrochemical, spectroscopic and photo-physical properties have allowed us to clarify the effect produced by the location of the organometallic arrays (ferrocenyl or cyrhetrenyl) on electronic delocalization, the proclivity of the metals to undergo oxidation and their emissive properties. Theoretical studies based on Density Functional Theory (DFT) calculations on the two compounds have also been carried out in order to rationalize the experimental results and to assign the bands detected in their electronic spectra. The cytotoxic activities of compounds 1 and 2 against human adenocarcinoma cell lines [breast (MCF7 and MDA-MB-231) and colon (HCT-116)] reveal that imine 2 has a greater inhibitory growth effect than 1 and it is ca. 1.8 times more potent than cisplatin in the triple negative MDA-MB 231 and in the cisplatin resistant HCT-116 cell lines. A comparative study of their effect on the normal and non-tumour human skin fibroblast BJ cell lines is also reported.