2. Universidad Cardenal Herrera-CEU

Metal complexes have gained a huge interest in the biomedical research in the last decade because of the access to unexplored chemical space with regards to organic molecules and to present additional functionalities to act simultaneously as diagnostic and therapeutic agents. Herein, we evaluated the interaction of two polytopic polyaza ligands and their zinc complexes with DNA and RNA by UV thermal denaturation, fluorescence and circular dichroism spectroscopic assays. The zinc coordination was investigated by X-ray diffraction and afforded the structure of the binuclear zinc complex of PYPOD. Thermal denaturation of DNA and RNA and fluorimetry analysis revealed preferential binding of the zinc-PHENPOD complexes towards GC-containing DNA in contrast to the free ligands. On the other hand, PYPOD metal complexes, compared to the free ligand, stabilized AT-based DNA (B-form) better than AU-RNA (A-form). With regards to single stranded RNA, the binuclear complex of PHENPOD and the free ligand can efficiently identify polyadenylic acid (poly A) among other RNA sequences by circular dichroism spectroscopy. The antimicrobial activity in S. aureus and E. coli bacteria showed the highest activity for the free ligands and their trinuclear zinc complexes. This work can provide valuable insights into the impact of the nuclearity of polytopic polyaza ligands in the binding to DNA/RNA and the antimicrobial effect.

Two new ligands (TPB3P and TPB3Py) showing a strong stabilisation effect and good selectivity for G4 over duplex DNAs have been synthesised. The ligands hold three analogous polyamine pendant arms (TPA3P and TPA3Py) but differ in the central aromatic core, which is a triphenylbenzene moiety instead of a triphenylamine moiety. Both TPB3P and TPB3Py exhibit high cytotoxicity in MCF-7, LN229 and HeLa cancer cells in contrast to TPA-based ligands, which exhibit no significant cytotoxicity. Moreover, the most potent G4 binders have been encapsulated in liposomes and AS1411 aptamer-targeted liposomes reaching nanomolar IC50 values for the most cytotoxic systems.

We report the synthesis and characterization of the macrocyclic ligand 2,2′-((2-(3,9-bis(carboxymethyl)-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)azanediyl)diacetic acid (H4L) and several of its complexes with lanthanide ions. The structure of the free ligand was determined using X-ray diffraction measurements. Two N atoms of the pyclen moiety in the trans position are protonated in the solid state, together with the exocyclic N atom and one of the carboxylate groups of the ligand. The relaxivity of the Gd3+ complex was found to increase from 6.7 mM–1 s–1 at pH 8.6 to 8.5 mM–1 s–1 below pH ≈ 6.0. Luminescence lifetime measurements recorded from H2O and D2O solutions of the Eu3+ complex evidence the presence of a single complex species in solution at low pH (∼5.0) that contains two inner-sphere water molecules. DFT calculations suggest that the coordination environment of the Ln3+ ion is fulfilled by the four N atoms of the pyclen unit, two oxygen atoms of the macrocyclic acetate groups, and an oxygen atom of an exocyclic carboxylate group. The two inner-sphere water molecules complete coordination number nine around the metal ion. At high pH (∼9.3), the lifetime of the excited 5D0 level of Eu3+ displays a biexponential behavior that can be attributed to the presence of two species in solution with hydration numbers of q = 0 and q = 1. The 1H NMR and DOSY spectra recorded from solutions of the Eu3+ and Y3+ complexes reveal a structural change triggered by pH and the formation of small aggregates at high pH values.

We present a set of donor radii for the rare-earth cations obtained from the analysis of structural data available in the Cambridge Structural Database (CSD). Theoretical calculations using density functional theory (DFT) and wave function approaches (NEVPT2) demonstrate that the Ln-donor distances can be broken down into contributions of the cation and the donor atom, with the minimum in electron density (ρ) that defines the position of (3,–1) critical points corresponding well with Shannon’s crystal radii (CR). Subsequent linear fits of the experimental bond distances for all rare earth cations (except Pm3+) afforded donor radii (rD) that allow for the prediction of Ln-donor distances regardless of the nature of the rare-earth cation and its oxidation state. This set of donor radii can be used to rationalize structural data and identify particularly weak or strong interactions, which has important implications in the understanding of the stability and reactivity of complexes of these metal ions. A few cases of incorrect atom assignments in X-ray structures were also identified using the derived rD values.