Are the metal identity and stoichiometry of metal complexes important for colchicine site binding and inhibition of tubulin polymerization?

Quite recently we discovered that copper(II) complexes with isomeric morpholine-thiosemicarbazone hybrid ligands show good cytotoxicity in cancer cells and that the molecular target responsible for this activity might be tubulin. In order to obtain better lead drug candidates, we opted to exploit the power of coordination chemistry to (i) assemble structures with globular shape to better fit the colchicine pocket and (ii) vary the metal ion. We report the synthesis and full characterization of bis-ligand cobalt(III) and iron(III) complexes with 6-morpholinomethyl-2-formylpyridine 4N-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL1), 6-morpholinomethyl-2-acetylpyridine 4N-(4-hydroxy-3,5-dimethylphenyl)-3-thiosemicarbazone (HL2), and 6-morpholinomethyl-2-formylpyridine 4N-phenyl-3-thiosemicarbazone (HL3), and mono-ligand nickel(II), zinc(II) and palladium(II) complexes with HL1, namely [CoIII(HL1)(L1)](NO3)2 (1), [CoIII(HL2)(L2)](NO3)2 (2), [CoIII(HL3)(L3)](NO3)2 (3), [FeIII(L2)2]NO3 (4), [FeIII(HL3)(L3)](NO3)2 (5), [NiII(L1)]Cl (6), [Zn(L1)Cl] (7) and [PdII(HL1)Cl]Cl (8). We discuss the effect of the metal identity and metal complex stoichiometry on in vitro cytotoxicity and antitubulin activity. The high antiproliferative activity of complex 4 correlated well with inhibition of tubulin polymerization. Insights into the mechanism of antiproliferative activity were supported by experimental results and molecular docking calculations.

Ferronematic Co(II) Complex: An Active Filler for Magnetically Actuated Soft Materials.

Ferronematics that are generally based on nematic liquid crystals (LCs) doped with magnetic nanoparticles, synergistically taking advantage of the anisotropic and flow characteristics of the nematic host and the magnetic susceptibility of the dopant, have powerful applications as magnetically actuated soft materials. In this work, a Co(II) complex, which alone presents both characteristics, is built with a salen-type ligand 3,5-dichlorosubstituted at the aromatic nuclei and has a tetramethyldisiloxane spacer, which makes it one of the few metallomesogens containing this structural motif. Paramagnetic crystals, through heat treatment above 110 °C, change into magnetic nematic LCs. Applying a perpendicular magnetic field of 50 mT, the nematic droplets align two by two through dipole-dipole interactions. By incorporating it into a silicone matrix consisting mainly of polydimethylsiloxane, a 3D printable ink is formulated and crosslinked under various shapes. In this environment, the cobalt complex is stabilized in an LC state at room temperature and, due to its anisotropy, facilitates the mechanical response to magnetic stimuli. The resulting objects can be easily manipulated on fluid or rough surfaces using external magnetic fields, behave like magnets by themselves, and show reversible locomotion.

Some Theoretical and Experimental Evidence for Particularities of the Siloxane Bond.

The specific features of the siloxane bond unify the compounds based on it into a class with its own chemistry and unique combinations of chemical and physical properties. An illustration of their chemical peculiarity is the behavior of 1,3-bis(2-aminoethylaminomethyl)tetramethyldisiloxane (AEAMDS) in the reaction with carbonyl compounds and metal salts, by which we obtain the metal complexes of the corresponding Schiff bases formed in situ. Depending on the reaction conditions, the fragmentation of this compound takes place at the siloxane bond, but, in most cases, it is in the organic moieties in the ß position with respect to the silicon atom. The main compounds that were formed based on the moieties resulting from the splitting of this diamine were isolated and characterized from a structural point of view. Depending on the presence or not of the metal salt in the reaction mixture, these are metal complexes with organic ligands (either dangling or not dangling silanol tails), or organic compounds. Through theoretical calculations, electrons that appear in the structure of the siloxane bond in different contexts and that lead to such fragmentations have been assessed.

Dual crystalline-amorphous salen-metal complexes behave like nematic droplets with AIEgens vistas.

A series of metal salen complexes, original in view of the presence in their structure of a highly flexible and hydrophobic spacer, were prepared on the basis of the reaction of 1,3-bis(3-aminopropyl)tetramethyldisiloxane with 3,5-dichloro-, 3,5-dibromo- and 3-hydroxy-salicylaldehyde and various metal ions (Co2+, Ni2+, Cu2+ and Zn2+). The isolated products were completely characterized from the structural point of view by FTIR, NMR, elemental analysis and single crystal X-ray diffraction, and further investigated from the perspective of the behavior induced mainly by the structural peculiarities. Emphasis is placed on self-assembly properties, both in bulk and in solution, depending on temperature, solvent nature and concentration, including thermotropic and lyotropic liquid crystals (LC). LCs that appear in the form of nematic toroidal droplets have been fully demonstrated by polarized optical microscopy (POM), differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS) and fluorescence anisotropy studies. The fluorescence analysis results revealed the aggregation-induced emission (AIE) phenomenon, where the emission occurs only for liquid crystals, with a few exceptions. Because these complexes can exist in both amorphous and crystalline states, it raised the question of how properties, such as electrical, change when switching from one state to another. These were well highlighted by DSC, BDS, PXRD, FTIR and fluorescence anisotropy.