Synthesis, characterisation and cytotoxic activity evaluation of new metal-salen complexes based on the 1,2-bicyclo[2.2.2]octane bridge

Abstract

Diaminobicyclo[2.2.2]octane was used as starting material for the preparation, in solution or in a ball-mill, of a salen ligand. Five metal salen complexes were prepared in high yield and their cytotoxic activities were evaluated against HCT116 cell lines. Original manganese salen complex displayed the highest activity with a potency 16 fold higher than the one of cisplatin, demonstrating the benefit of the bridging backbone, compared to other salen systems. An alternative preparation route for this complex by mechanochemistry was also performed. File list (2) download file view on ChemRxiv MetalSalenChemRxiv.pdf (403.58 KiB) download file view on ChemRxiv MetalSalenChemRxivSI.pdf (0.94 MiB) Synthesis, characterisation and cytotoxic activity evaluation of new metalsalen complexes based on the 1,2-bicyclo[2.2.2]octane bridge

Multigram Mechanochemical synthesis of a Salophen Complex: A Comparative Analysis

“…54 Alternatively, these species can be produced mechanochemically via neat or LAG conditions. 1,15,49,55 In a typical reaction, 5-bromosalicylaldehyde and a diamine (ethylenediamine, and 1, 2-phenylenediamine for salen and salophen ligands, respectively) were ground together in a 15 mL milling jar with an 8 mm diameter ball (both stainless steel); see Figure 3a. The mechanochemical synthesis of the ligands proceeded smoothly and achieved full conversion after 2 h. Since the reaction produced water as byproduct, the solids obtained were oven-dried to afford free-flowing yellow powders.…”

“…These species, synthesized in the presence of sodium chloride as a salt additive, were produced in moderate to good yields (i.e., 62 to 98%) in the milligram scale (i.e., 9.8 to 129 mg). 49 Although the methods described above opened opportunities for the mechanochemical synthesis of these species, the reported synthesis still depended on either the use of solvent additives to accelerate the reaction or were performed only at small/medium scale. Conventional solution-based methods at industrial scales would vastly increase energy usage due to solvent removal.…”

“…32 g of ligand required 200 mL of methanol under reflux conditions, with an additional 500 mL of diethyl ether for workup. This methodology results in high E-factors − , (i.e., total weight of all the solvents used in this synthesis divided by the weight of isolated product). This severely impacts the practical industrial implementation of such complexes, since large scale synthesis leaves a large environmental footprint.…”

Solvent-Free Mechanochemical Diaza-Cope Rearrangement

“…We next shift our attention to the application aspect of mechanochemical-driven DCR to prepare synthetically useful metal complexes. − Salen complexes, being named one of the privileged chiral catalysts, display superior asymmetric catalytic properties for a wide range of organic transformations . Their syntheses are often multistep processes in the presence of organic solvents.…”

Design, Sustainable Synthesis and Biological Evaluation of a Novel Dual α2A/5-HT7 Receptor Antagonist with Antidepressant-Like Properties

“…In the last decade, mechanochemistry, and in particular medicinal mechanochemistry [22,23], has been recognized as an innovative technique for the generation of various organic compounds as well as producing pharmaceutically relevant fragments and functionalities [24][25][26]. Taking into account the benefits of employing a solid-state approach over classic in-batch procedures (i.e., increased reaction yield, reduction of time, decreased use of organic solvents) [27,28], we developed a mechanochemical approach for the synthesis of the designed derivatives 6-19 (Scheme 1).…”