Resumen de Carboranylphosphinic acids: a new class of purely inorganic ligands to generate polynuclear compounds and multifunctional nanohybrid materials for biomedical applications /
Summary of the thesis The research presented in this thesis includes the synthesis and characterization of carboranylphosphinic and carboranylphosphonic acids to use them as versatile purely inorganic building blocks. In the Chapter 2 has been shown that, in a similar manner to organic phosphinates, purely inorganic carboranyl-phosphinates can be prepared in very good to excellent yields, while the preparation of carboranylphosphonates does not follow the same tendency. Carboranylphosphonates cannot be so easily made, at least with described in this PhD thesis methods (Chapter 3). Carboranylphosphinic acids have been prepared both with the ortho-, and meta-carborane. The hydrogen in the H–P unit of the carboranylphosphinate has been easily exchanged by D from the deuterated NMR solvent, although rate differences have been noticed depending on the adjacent carborane carbon substituent and the salt utilized. The carborane influence has been noticed in the pK of the phosphinate, which is more negative for the m-carboranyl and more positive for the o-carboranyl when are compared with the organic phenyl. Having enough information on the different phosphinic acids of ortho- and meta-carborane, for further use we put our attention on the meta-carborane derivatives due to its enhanced stability compare to ortho-isomer derivatives.
In the Chapter 4 we have studied the coordination chemistry of m-carboranylphosphinate ligands with the first and the second raw transition metals in alcohol media and initiated studies in aqueous media, aiming to generate purely inorganic coordination polymers (CPs). The X-Ray structures show 1D phosphinate CPs of MnII and CdII and the formation of salts of CoII and NiII. Also, a new 1D polymer with ZnII and a carboranylphosphinate bridged dinuclear CuII compound have been synthesized. The polymeric structure of MnII coordination polymer was maintained in the presence of 2,2’-bpy chelating ligand generating a new 1D polymeric manganese derivative, while the reactivity of MnII CPs with water led to the breakage of the polymers into fragments of low nuclearity. Contrary, the polymeric structure of CdII CP remains in the presence of H2O. Magnetic measurements of manganese polynuclear compounds were carried out showing in all cases, weak antiferromagnetic interactions between the manganese atoms.
Further, in the Chapter 4 we describe some studies of the reactivity of 1-R-7-OPH(OH)-1,7-closo-C2B10H10 and Na[1-OPH(O)-1,7-closo-C2B10H11] (R= CH3, H) ligands with MnII and CoII in aqueous media revealing that the substituent, -CH3 or -H, on the other C of the cluster of the carboranylphosphinate ligand and the starting metal salt (MnCO3 or MnCl2) can play a role in the final molecular structure of the complex. Thus, the –CH3 substituent at the Cc was found to be favorable to produce polynuclear complexes, while the –H substituent at the Cc lead only mononuclear complexes or salts. The last part of the thesis (Chapter 5) deals on the capacity of the novel carboranylphosphinate ligand to bind onto the surface of magnetic nanoparticles (MNPs) via coordination to the iron atoms as a phosphinate bidentated bridging ligand (1-MNPs), and provides an understanding of how the environment influences on the strength of this bond. Of particular relevance is what refers to the stability of 1-MNPs before and after sterilization under autoclave conditions. Biological studies confirmed the uptake of 1-MNPs by the cultured cells (hCMEC/D3 and A172) and the presence of the m-carboranylphosphinate in dried-cells samples. Quantification of 1-MNPs uptake by cells displayed that glioblastoma A172 cells presented larger cellular iron contents than brain endothelial (hCMEC/D3) cells. In terms of drug safety, we have shown that the systemic administration of the 1-MNPs nanohybrids does not show major signs of toxicity in mice, supporting its potential translation into the biomedical setting.
