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Leishmaniasis is one of the world's most neglected diseases with a worldwide prevalence of 12 million people. There are no effective human vaccines for its prevention, and outdated drugs hamper treatment. Therefore, research aimed at developing new therapeutic tools to fight leishmaniasis remains a crucial goal today. With this purpose in mind, here, we present 10 new compounds made up by linking alkylated ethylenediamine units to pyridine or quinoline heterocycles with promising in vitro and in vivo efficacy against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani, and Leishmania braziliensis species. Three compounds (2, 4, and 5) showed a selectivity index much higher in the amastigote form than the reference drug glucantime. These three derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than glucantime tested at an IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than glucantime. The mechanism of action of these compounds has been studied, showing alterations in glucose catabolism and leading to greater levels of iron superoxide dismutase inhibition. These molecules could be potential candidates for leishmaniasis chemotherapy due to their effectiveness and their ready synthesis.

Triazolopyridine-pyridine amine ligands are easily obtained by means of either thermal- or copper(II)-mediated reactions. Starting from a readily accessible iodo derivative of triazolopyridine-pyridine and different amines, this new family of compounds combines aromatic and aliphatic nitrogen atoms with promising coordinating properties. Furthermore, chemical derivatization of a new triazolopyridine-pyridine diamine compound, N1-[6-([1,2,3]triazolo[1,5-a]pyridin-3-yl)pyridin-2-yl]ethan-1,2-diamine, allows the preparation of several remote-pyridine-containing ligands.

A scorpionate Zn2+ complex, constituted by a macrocyclic pyridinophane core attached to a pendant arm containing a fluorescent pyridyl-oxadiazole-phenyl unit (PyPD), has been shown to selectively recognize chloride anions, giving rise to changes in fluorescence emission that are clearly visible under a 365 nm UV lamp. This recognition event has been studied by means of absorption, fluorescence, and NMR spectroscopy, and it involves the intramolecular displacement of the PyPD unit by chloride anions. Moreover, since the chromophore is not removed from the system after the recognition event, the fluorescence can readily be restored by elimination of the bound chloride anion.

The binding properties of HL1, HL2, and HL3 ligands toward Cu(II) and Zn(II) ions, constituted by tetraaza-macrocyclic rings decorated with pyrimidine pendants, were investigated by means of potentiometric and UV spectrophotometric measurements in aqueous solution, with the objective of using the related HL-M(II) (HL = HL1–HL3; M = Cu, Zn) complexes for the preparation of hybrid MWCNT-HL-M(II) materials based on multiwalled carbon nanotubes (MWCNTs), through an environmentally friendly noncovalent procedure. As shown by the crystal structure of [Cu(HL1)](ClO4)2, metal coordination takes place in the macrocyclic ring, whereas the pyrimidine residue remains available for attachment onto the surface of the MWCNTs via π–π stacking interactions. On the basis of equilibrium data showing the formation of highly stable Cu(II) complexes, the MWCNT-HL1-Cu(II) material was prepared and characterized. This compound proved very stable toward lixiviation processes (release of HL1 and/or Cu(II)); thus, it was used for the preparation of its reduced MWCNT-HL1-Cu(0) derivatives. X-ray photoelectron spectroscopy and transmission electron microscopy images showed that MWCNT-HL1-Cu(0) contains Cu(0) nanoparticles, of very small (less than 5 nm) and regular size, uniformly distributed over the surface of the MWCNTs. Also, the MWCNT-HL1-Cu(0) material proved very resistant to detachment of its components. Accordingly, both MWCNT-HL1-Cu(II) and MWCNT-HL1-Cu(0) are promising candidates for applications in heterogeneous catalysis.

The synthesis, acid-base behavior and Pb2+ coordination chemistry of the new aza-scorpiand like ligand 5-[2-(N-2-fluorenyl)ethylamino]-2,5,8-triaza[9]-2,6-pyridinophane (L1) have been studied by potentiometry, NMR and spectrofluorimetric titrations, and the results are compared with those obtained for the related compounds L2, lacking the fluorenyl group, and L3, the macrocycle lacking the pendant arm. The crystal structures obtained for complexes [PbL1][PbL1Cl](NO3)Cl2·4H2O (1) and [PbL3](ClO4)2 (2) reveal that the metal ion is located over the plane defined by the nitrogen atoms of the macrocyclic core due to its inability to accommodate the large Pb2+ ion in the macrocyclic cavity. For L1, the secondary amino group of the pendant arm is implicated in the coordination of the metal ion, although the stereoactive lone pair of Pb2+ prevents the closed conformation associated with the coordination of metal ions in aza-scorpiand derivatives. The kinetics of the acid-promoted dissociation of the ligand from the Pb2+ complexes with the three ligands have been studied using stopped-flow with simultaneous absorbance and fluorescence detection. The results indicate that in spite of their similarity, the dissociation of the metal ion occurs with very different rates in the three complexes. During the course of the kinetic studies evidence was obtained for the occurrence of a photochemical process that leads to ligand degradation with the unexpected elimination of one CH2CH2 fragment from the macrocyclic core.

The anti-chagasic activity of a series of eleven derivatives of aza-scorpiand-like macrocycles, some of them newly synthesised, was assayed. The four compounds with the best selectivity indices in vitro were subjected to in vivo assays. Tests in a murine model of the acute phase of Chagas disease showed a two-fold reduction in parasitaemia compared to that with benznidazole. Furthermore, compounds 7 and 11, with 4-pyridine and phenanthroline substituents in the lateral chain, caused a remarkable decrease in parasitaemia reactivation during the chronic phase after inducing immunosuppression in mice. These activity studies were complemented by measuring their inhibitory effect towards the antioxidant parasite-specific enzymes, iron superoxide dismutase (Fe-SOD) and trypanothione reductase, the metabolites excreted after treatment and ultrastructural alterations. The ability of the selected macrocycles to complex with Fe(II) and Fe(III) was studied using potentiometric methods. Detailed molecular dynamics studies provided interesting pointers about the way in which the compounds approach and modify the active centre of Fe-SOD. The activity, low toxicity, stability, low cost of the starting materials and straightforward synthesis make these compounds appropriate molecules for the development of affordable anti-chagasic agents.

Green nanostructured heterogeneous catalysts were prepared via a bottom-up strategy. Designed ligands were synthesized joining covalently an electrondeficient pyrimidine residue and a scorpiand azamacrocycle. The desired molecular properties were easily transferred to nanostructured materials in two steps: first, exploiting their spontaneous chemisorption onto multi-walled carbon nanotubes (MWCNTs) via the pyrimidinic moiety in water at room temperature, then, taking advantage of the easy coordination of Pd(II) to the azamacrocycle in the same conditions. An evenly distribution of catalytic centres was obtained on the MWCNTs surface. Catalytic properties of these materials were assessed toward the Cu-free Sonogashira cross-coupling, leading to significant improvements in terms of yields and reaction conditions, especially when considering the possibility to maintain yields of 90%, or above, in a feasible amount of time (2 h), while working under green conditions (water, 50 °C, aerobic atmosphere). The catalysts proved to be reusable for several cycles with good yields.