Metal-based compounds play a fundamental role in inorganic medicinal chemistry and the most important anticancer agents, approved worldwide as chemotherapeutic drugs, contain metals as the active component (i.e. platinum in cisplatin). Several examples of metal containing anticancer drugs are reported, including gold, ruthenium, silver, titanium, copper, cobalt. Surprisingly, Tellurium-based compounds never attracted the curiosity of the scientific community and tellurium chemistry with relevance to biological systems is poorly developed. Only recently, two Tellurium containing species have been investigated in clinical trials as anticancer agents, named AS101 (Ammonium trichloro(dioxoethylene-O,O’)tellurate) and Octa O-Bis-(R,R)-tartarate ditellurane (SAS)). These species, whose target are the cysteine residues of proteins (they act as cysteine protease inhibitors), are not stable in physiological conditions and decompose forming oxo-chloro tellurium(IV) compounds that are retained to be the real active species. Inspired by the results obtained with the above mentioned Te species, we developed a series of analogues of Te(IV)-based compounds with the aim to enhance the physiological stability in order to clarify the biological mechanism of action of these species. The coordination sphere of tellurium has been modified with different ligands, tuning the steric electronic properties. The stability has been studied experimentally via multinuclear NMR spectroscopy (1H, 13C, 125Te NMR) in solution with accurate experiments in the presence of different equivalents of water. The experimental data have been combined with theoretical calculations that confirmed the stability trend. More than twenty new compounds have been synthesized and characterized with many spectroscopic techniques (multinuclear NMR (1H, 13C, 19F and 125Te-NMR), IR, Elem. Anal., Mass spectroscopy) including X ray structures. Reaction mechanisms for the formation of the new species have been proposed based on critical analyses of experimental and theoretical results. These species showed very high antibacterial potency, in particular against Gram negative E. Coli bacteria, with the activity produced by the hydrolysed product [TeOCl3]-.