Tailoring the local environment around metal ions: a solution chemical and structural study of some multidentate tripodal ligands

Abstract

Manganese(II), copper(II) and zinc(II) complexes of four polydentate tripodal ligands (tachpyr (N,N',N''-tris (2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane), trenpyr (tris[2-(2-pyridylmethyl)aminoethyl]amine, tach3pyr (N,N',N''-tris(3-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane) and tren3pyr (tris[2-(2-pyridylmethyl)aminoethyl]amine)) were characterized in both solution and solid states. A combined evaluation of potentiometric, UV-VIS, NMR and EPR data allowed the conclusion of both thermodynamic and structural information about the complexes formed in solution. The four tailored polydentate tripodal ligands studied here exhibit a high thermodynamic stability, and a variety of coordination environments/geometries for the studied transition metal ions. Our data indicate that tachpyr is a more efficient zinc(II) chelator and a similar copper(II) chelator compared to trenpyr. Considering the higher number of N-donors and conformational flexibility of trenpyr, as well as the energy demanding switch to the triaxial conformation required for metal ion binding of tachpyr, the above observation is surprising and is very likely due to the encapsulating effect of the more rigid tachpyr skeleton. This relative binding preference of tachpyr for zinc(II) may be related to the observation that zinc(II) is one of the principal metals targeted by tachpyr in cells. In contrast, trenpyr is a considerably more efficient manganese(II) chelator, since it acts as a heptadentate ligand in the aqueous Mn(trenpyr) complex. The crystal structures of copper(II) and zinc(II) complexes of tachpyr indicated important differences in the ligand conformation, induced by the position of counter ions, as compared to earlier reports. The closely related new ligands, tach3pyr and tren3pyr, have been designed to form oligonuclear complexes. Indeed, we obtained a three dimensional polymer with a copper(II)/tren3pyr ratio of 11/6. Within this metal-organic framework, three distinctly different copper geometries can be identified: square pyramidal, trigonal bipyramidal and tetrahedral. Two square pyramidal and four trigonal bipyramidal copper centres create a hexanuclear subunit with a large inside cavity. These moieties are linked by tetrahedral copper(II) centres, constructing the three-dimensional polymer structure. The formation of such polynuclear complexes was not detected in solution. Both tach3pyr and tren3pyr form only mononuclear complexes with square pyramidal and trigonal bipyramidal geometries, respectively.

On the copper(ii) binding of asymmetrically functionalized tripodal peptides: solution equilibrium, structure, and enzyme mimicking

“…Accordingly, tripodal ligands are applied in diverse fields of chemistry, such as metal sensing, 1 metalloenzyme modelling, [2][3][4][5][6][7] and stabilization of reactive species and intermediates 8,9 and even for the development of molecular motors. 10 Some tripodal ligands and/or their metal complexes show high tendency to selfassembly, creating metal-organic frameworks, 11 metallocages with colorful compositions, 12 hydrogels 13 or other mesophase structures, 14 thus expanding their application to supramolecular chemistry as well. The advantages of peptide-type tripodal ligands in coordination chemistry have been recognized in the last few decades.…”

Anion-induced structural diversity in cadmium coordination polymers of 4-aminobenzonitrile: a structural and DFT study

“…Depending on the extension in space, they can be one, two or three-dimensional. Several key factors control self-assembly of CPs like the coordination environment of the metal ion, 25,26 ligand functionality, 27 ligand flexibility, [28][29][30] metal to ligand ratio, 31,32 temperature, 33,34 pH, 35 solvent, [36][37][38] anions [39][40][41][42][43] and non-covalent interactions. [44][45][46][47][48][49] Among these factors, anions are one of the most important to be noted.…”

Design and Synthesis of Poly(2,2′-Bipyridyl) Ligands for Induction of Cell Death in Cancer Cells: Control of Anticancer Activity by Complexation/Decomplexation with Biorelevant Metal Cations

“…For example, desferrioxamine (DFO), a first line agent of the treatment of an iron overload, was utilized in clinical trials for the treatment of hepatocellular carcinoma (Scheme ). It has also been reported that copper chelators induce the cell death in colon cancer cells via the generation of reactive oxygen species. − Tripodal ligands such as N , N′ , N ″-tris­(2-pyridylmethyl)- cis , cis -1,3,5-triaminocyclohexane (tachpyr) − provide additional donor sites and affect the steric environment around the metal center allowing more efficient metal chelating, resulting in the activation of intracellular cell death mechanisms. However, care needs to be exercised in the use of metal chelators, because of the side effects possibly due to the nonspecific complexation with intracellular metal cations.…”