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

Abstract

The synthesis and characterization of two novel and isomeric hybrid ferrocenyl/cyrhetrenyl aldimines [(η-CH)Fe{(η-CH)-CH[double bond, length as m-dash]N-(η-CH)}Re(CO)] (1) and [(η-CH)Fe{(η-CH)-N[double bond, length as m-dash]CH-(η-CH)}Re(CO)] (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(η-CH)" and "Re(CO)" 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.

Therapeutic and Diagnostic Applications of Multimetallic Rhenium(I) Tricarbonyl Complexes

“…For example, the aldimine-linked FcÀ Re conjugates, 66 and 67 (Figure 13), have been studied, operating under the hypothesis that the two metallic fragments can act synergistically. [61] Notably, 67 exhibits cytotoxicity greater than cisplatin in both breast cancer MDA-MB-231 and colon cancer HCT-116 cells. By contrast, 66 is less active, thus demonstrating how subtle structural differences in these complexes can have significant effects on biological activities.…”

“…Re(CO) 3 has also been attached to Fc for designing new anticancer agents. For example, the aldimine‐linked Fc−Re conjugates, 66 and 67 (Figure 13), have been studied, operating under the hypothesis that the two metallic fragments can act synergistically [61] . Notably, 67 exhibits cytotoxicity greater than cisplatin in both breast cancer MDA‐MB‐231 and colon cancer HCT‐116 cells.…”

Ferrocifens labelled with an infrared rhenium tricarbonyl tag: synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells

“…19 With the aim of gaining information on the distribution of ferrocifens in cancer cells, we decided to synthesize three new ferrocenyl complexes labelled with the CpRe(CO)3 tag (4-6, Chart 1) but still possessing the Fc-double bond -phenol motif, which has been found to be essential for expression of their cytotoxicity in vitro. 20 The synthesis and antiproliferative activity of two hybrid ferrocenyl/cyrhetrenyl aldimines has recently been published, 21 but complexes 4-6 represent the first members of the ferrocifen family bearing these two organometallic units. Cytotoxicity studies and partition coefficient measurements were then performed on these new complexes, together with enzymatic oxidation studies by the horseradish peroxidase / H2O2 system, quantification of the complexes in cell pellets by transmission FT-IR spectroscopy and of rhenium and iron in by ICP-OES.…”

Design of Rhenium Compounds in Targeted Anticancer Therapeutics

“…including Re(IV)/Mo(VI), Zn(II)/Re(IV) or Re(I)/Tc(I) combinations [33][34][35]. Among them the Re-Fe [36], Re-Au (7, Fig. 1) [37] and Re-Pt [38] heterobimetallic complexes showed a good cytotoxic activity combined with a strong fluorescence associated with a metal-to-ligand charge transfer making same useful theragnostic candidates.…”