Binding ability of some commercially available and synthesized ligands towards metal cations of environmental and biological interest

The research activity performed during the three years of PhD course in Chemical Sciences concerned the speciation study of bivalent and trivalent metal cations in the presence of ligands of different nature and applications, in ionic medium NaCl, the main inorganic component of mostly natural and biological fluids. The term “speciation” is used to indicate the distribution of the physical and chemical forms in which a component is present in a system. Since the different forms of a substance may have various behavior towards humans and environment, the study of speciation becomes essential to have information about their bioavailability, toxicity and environmental impact. To have a complete idea about the chemical speciation of a substance in a multicomponent system, it is necessary to consider the processes of formation of all the possible chemical species, to evaluate the interactions with other species in the system and the effect of experimental conditions (e.g. metal-ligand concentration ratio, temperature, ionic strength). The ligands of interest can be classified into two categories: 1. commercially available molecules, such as Gantrez® AN169 (GTZ4-), citric acid (Cit3-) and orthosilicic acid (H2SiO42-); 2. products of synthesis, like the 3-hydroxy-4-piridinones, derivatives of the 1,2-dimethyl-3-hydroxy-4-piridinone, commercially known as Deferiprone, and approved as orally drug for the treatment of patients affected by iron overload. For all the system investigated, the study of speciation took into account the acid – base properties of each ligand, in term of reactions of protonation, and of the metal cations (reactions of hydrolysis) and the dependence on ionic strength and on temperature of the stability constants was modeled by a modified Debye-Hückel equation. The analysis of experimental data, allowed to determine different speciation models, considered the best possible ones on the basis of criteria such as simplicity, probability, formation percentages of species, statistical parameters and literature comparison. Gantrez® AN169 is a synthetic copolymer of methyl vinyl ether (MVE) and maleic anhydride (MA) having several applications in industrial (textiles, paper, adhesives, coatings), cosmetics, pharmaceutical and oral care product fields. This compound presents an anhydride functional group; in water it can hydrolyzes slowly in the corresponding dicarboxylic acid, the Gantrez® S. A potentiometric investigation on the interactions of Gantrez® AN169 with bivalent (M2+ = Mg2+, Sn2+, Zn2+) and trivalent (M3+ = Al3+) metal cations was carried out in different conditions of ionic strength (0.10 < I/mol L-1 < 1.00) in NaCl(aq) and temperatures (283.15 < T/K < 318.15). This study led to the refinement of speciation models characterized by complexes (Mp(GTZ)qHr) with various stoichiometry, such as protonated, simple metal-ligand, polynuclear and hydrolytic mixed species. In all the cases, the stability constant values of the complexes increase increasing the temperature and decrease increasing the ionic strength. The investigation on the interactions of orthosilicic acid, the main form of bioavailable silica for humans and animals, in the presence of Al3+, at I = 0.10 and 1.00 mol L-1 in NaCl(aq) and T = 298.15 K, showed the formation of the protonated [AlH(H2SiO4)]2+ species, in accordance with the speciation model reported in the literature by Spadini et al. The synthesis and the characterization of 3-hydroxy-4-piridinones (3,4-HPs) was performed during a period of six months of research abroad under the supervision of the Prof. M. Amélia Santos, at the Centro de Química Estrutural of the Instituto Superior Técnico (Universidade de Lisboa). These products are a class of bidentate compounds, characterized by an aromatoid N-heterocycle with hydroxyl and ketone groups in ortho, can be effective in all biological conditions and do not cause problems of toxicity, prize and oral activity. They can be synthesized from the 3,4-hydroxypyranone (maltol) through a reaction of protection of the –OH group with a benzyl group, followed by a double Michael-type addition with opening and closure of the aromatoid ring. These compounds can be further derivatized via the formation of amide bonds and final deprotection of the hydroxyl group with a hydrogenation catalyzed by 10% Pd/C. The products synthesized were monosubstituted 3-hydroxy-4-piridinone derivatives of aspartic anhydride (called A5 and A6) and disubstituted compounds of DTPA bisanhydride (A7) and of NTA (A8). The study of speciation of these ligands and of other four compounds (KC, PropKC, Py-Orn and A3) synthesized by the group of Prof. M. Amélia Santos, started from the investigation of their acid-base behavior, by performing UV-Vis spectrophotometric and spectrofluorimetric measurements carried out at I = 0.15 mol L-1 in NaCl(aq) and T = 298.15 K and at T = 310.15 K (physiological conditions). The analysis of experimental data allowed to refine protonation constants values which are quite in accordance either between the two analytical techniques or with the literature data. Furthermore, the binding ability of the 3,4-hydroxypiridinones towards the Al3+ was studied through potentiometric and spectrophotometric experiments performed at T = 298.15 K and I = 0.15 mol L-1 in NaCl(aq). The speciation models were characterized by species (AlpLqHr) with different stoichiometry, on the basis of the different functional groups present on the ligands. For example, focusing on the simple AlL species determined, if present in the speciation models, at I = 0.15 mol L-1 in NaCl(aq) and T = 298.15 K, it was possible to observe that the stability of the complexes follows the trend: Al(Py-Orn) > Al(A5) > Al(A6) > Al(A3) > Al(KC) ~ Al(PropKC). Furthermore, the interactions between the disubstituted 3-hydroxy-4-piridinone derivatives and bivalent metal cations such as Ca2+, Cu2+ and Zn2+ were investigated by performing UV-Vis spectrophotometric measurements at I = 0.15 mol L-1 in NaCl(aq) and T = 298.15 K, in the pH range 2 - 11. The elaboration of the experimental data led to the determination of speciation schemes constituted by protonated, simple metal – ligand and polynuclear species. Finally, the sequestering ability of all the ligands studied during the work presented in the thesis towards the chosen metal cations was investigated with the calculation of the pL0.5, an empirical parameter already proposed by the research group, which represents the total concentration of ligand necessary to sequester the 50% of a given ion present in trace in solution, on varying the experimental conditions (pH, ionic strength and temperature). Form the analysis of the pL0.5 values obtained, it was found that in general the sequestering ability increases with increasing pH values and temperature and decreases by increasing the ionic strength. For example, in the case of the Al3+/commercially available ligands systems, the sequestering ability at pH = 4.0, I = 1.00 mol L-1 in NaCl(aq) and T = 298.15 K, follows the trend: Cit3- > GTZ4- > H2SiO42-, whilst at the same pH value and temperature but at I = 0.15 mol L-1 in NaCl(aq), the sequestration by the 3-hydroxy-4-priridinones toward the same metal cation is in the order: A7 > A8 > KC > A6 > Py-Orn > A5 > PropKC > A3.