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Complejos de ligandos azamacrocíclicos como miméticos de enzimas con actividad antioxidante

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Complejos de ligandos azamacrocíclicos como miméticos de enzimas con actividad antioxidante

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dc.contributor.advisor	Garcia-España Monsonis, Enrique
dc.contributor.advisor	Tejero Toquero, Roberto
dc.contributor.advisor	Llinares Berenguer, José Miguel
dc.contributor.author	Martínez Camarena, Álvaro
dc.contributor.other	Institut de Ciència Molecular	es_ES
dc.date.accessioned	2019-10-14T08:15:37Z
dc.date.available	2019-11-14T05:45:05Z
dc.date.issued	2019	es_ES
dc.date.submitted	11-10-2019	es_ES
dc.identifier.uri	https://hdl.handle.net/10550/71717
dc.description.abstract	The imbalance between the generation and clearance of reactive oxygen species (ROS) causes oxidative stress, which is related to a variety of health issues that include neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. In order to remove ROS, living organisms have developed a battery of protective enzymes, such as superoxide dismutases (SODs). Although SOD enzymes have shown therapeutic efficacy, their use has severe drawbacks such as the absence of oral activity, immunogenicity, short half-life and low cell permeability. Therefore, low-molecular weight mimetics may offer better outcomes regarding properties such as lack of antigenicity, good tissue penetrance, high stability, longer half-life in solution, and low production cost. A number of these low molecular SOD mimetics are complexes of polyamine ligands of either cyclic or open-chain topology. In this respect, it has been reported that several mononuclear or binuclear copper complexes of aza- macrocyclic ligands have SOD activities in vitro which rank among the highest ones so far reported for synthetic systems. A step forward to improve the activity, the likely-cell uptake and bio-distribution of these low molecular weight mimetics might be their incorporation in non-toxic nanoparticles (NPs). The grafting of the molecules to the surface of the nanoparticles may yield pre-concentration and amplification of the signal. The work here we present deals with the design, synthesis and study of seven new aza-macrocyclic ligands. The design of the ligands is based on the modification of the fundamental tetraazamacrocycle through three main ways: alkylation of the secondary amines, introduction of new functional groups in the pyridine derivative and elongation of the aza-macrocyclic moiety. In this thesis, we report the synthesis and characterization of the aforementioned seven new compounds, as well as the functionalization of four of them onto the surface of boehmite and silica NPs. Additionally, here we discuss on the acid base behavior of the ligands, and on their capability to coordinate Cu(II), Zn(II) and/or Fe(II), particularly at physiological pH. Finally, we present the SOD and catalase activity results of the studied complexes, both free in solution and grafted onto the surface of the NPs. Regarding the results, we should notice that all the studied ligands are capable to coordinate Cu(II), Zn(II) and/or Fe(II) in a quantitative way at physiological pH. Furthermore, the Cu(II) complexes present SOD activity, which is improved with the alkylation of the secondary amines, the addition of electron-withdrawing groups in para to the pyridinic moiety and the increase of the amount of coordinating amines in the macrocyclic chain. In addition, functionalization of the complexes onto the surface of boehmite NPs impressively enhance their SOD activity, what may be related with its positively charged surface, as we show in the last chapter of the thesis.	es_ES
dc.format.extent	402 p.	es_ES
dc.language.iso	es	es_ES
dc.subject	química supramolecular	es_ES
dc.subject	azamacrociclos	es_ES
dc.subject	actividad antioxidante	es_ES
dc.subject	superóxido dismutasa	es_ES
dc.subject	catalasa	es_ES
dc.title	Complejos de ligandos azamacrocíclicos como miméticos de enzimas con actividad antioxidante	es_ES
dc.type	doctoral thesis	es_ES
dc.subject.unesco	UNESCO::QUÍMICA	es_ES
dc.embargo.terms	1 month	es_ES