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Metastases rather than primary tumors are the leading cause for cancer death, and yet metastases are almost never the target of chemotherapy. At present, Ruthenium complexes have been found to offer new perspectives. Although a rather large number of studies on Ruthenium complexes have been published in the recent years, up to date in literature no examples of nanovectors carrying Ruhenium complexes for anticancer therapy are reported. At this aim, we have synthesized a new amphiphilic unimer able to coordinate Ruthenium complexes and to form liposomes. This unimer (DOPU) has been obtained from an uridine derivative by traightforward introduction of a pyridine function on the uracile base. The hydrophobic part of the molecule consists of a double C18 oleoyl chain. The ligand unimer DOPU has been afterward coordinated to Ru(III). Preliminary SANS, Cryo-TEM and DLS measurements have confirmed the presence of unilamellar and oligolamellar liposomes, as well as the existence of more complex structures like cubosomes. The findings in the present study open up new vistas for the application of lipid based supramolecular systems in Ruthenium anti-cancer therapy. The lodgment of Ruthenium complexes in amphiphilic nanovectors allows a higher amount of drug in the bloodstream compared to the case when it is administrated as a free complex. Furthermore, amphiphilic nanovectors are able to protect the Ruthenium complexes from enzymatic and/or environmental degradation that could otherwise occur during bloodstream circulation.

Nel presente lavoro di dottorato è descritta la sintesi di nuovi leganti chelanti, tridentati e tetradentati, derivati da carboidrati che, complessati a metalli di transizione, hanno fornito utili sistemi catalitici per processi di catalisi asimmetrica (epossidazione di stireni, ossidazione di solfuri e alchilazione di substrati allilici).

Bis(pyridine-2-carboxamides) were prepared from 1,2-diamines obtained from alpha-D-ghlcose and alpha-D-mannose. The ligands were assessed in molybdenum-catalyzed asymmetric allylic alkylations (AAA ...

The simple synthesis of new O,N,O′-tridentate ligands derived from carbohydrates is illustrated. The ligands are obtained by condensing 2-amino-α- d -glucosides or 2-amino-α- d -alloside with several 3,5-disubstituted-2-hydroxybenzaldehydes. The efficiency of the imines in the V(IV)-promoted asymmetric oxidation of thioanisole has been examined and ee's up to 60% have been achieved.

A strategy for the synthesis of new chiral salen type ligands derived from α- d -glucose and α- d -mannose is described. The compounds were obtained by introducing appropriate functions at the C2 and C3 positions of the sugar ring. The efficiency of the complexes in the epoxidation of styrenes was also examined and shown to give good results, for example, cis -β-methylstyrene was functionalised with ee’s of up to 86%.

Aiming to contribute to the design of new antitumoral drugs, we synthesized new hydrophilic Pt(II) complexes of general formula [PtCl 2 ( N , N ′)] containing nitrogen bidentate amine–imine and di-imine ligands derived from glucose. Some chemical properties were discussed. The X-ray molecular structure of [PtCl 2 (α- d -glucopyranoside-methyl-6-deoxy-6(2-(methylimino)methyl)pyridine) ( D ) was reported. [PtCl 2 (β- d -glucopyranosylimine- N -(2-pyridinylmethyl))] ( A ), which is well-soluble both in organic solvents and in water, was tested for cytotoxicity.

Readily available chiral bis(phosphinoesters) based on d -glucose, d -mannose and d -galactose have been prepared in only two steps and in large scale starting from inexpensive commercial precursors. Their Pd complexes catalyze the asymmetric desymmetrization of meso-cyclopent-4-ene-1,3-diol biscarbamate in ee’s up to 82%.

New chiral bis(phosphinoamides) based on glucose 1G and mannose 1M have been prepared. Their Pd complexes catalyze the asymmetric desymmetrization of meso-cyclopenten-2-ene-1,4-diol biscarbamate in high ee’s (up to 97%). Glucose and mannose moieties selectively promote formation of the opposite enantiomers, as a consequence of inverted steric motifs around the metal center.

A strategy for the preparation of a supported ‘salen-type’ Mn(III) catalyst derived from d -glucose is described. The compound has been prepared by introducing the ligand functions at positions 2 and 3 of the sugar, which has been subsequently anchored to a CHO-modified Wang resin through formation of a 4,6-O-benzylidene ring. The activity of the catalyst in the asymmetric epoxidation of styrenes has been investigated by using four different oxidants.

Ruthenium complexes offer new perspectives in cancer therapy; towards this aim we have synthesized a new amphiphilic unimer able to coordinate ruthenium complexes and to form liposomes.