Síntesis de compuestos de oro con ligandos n-acíclicos y n-heterocíclicosestudio de sus propiedades catalíticas y biológicas

Resum

ABSTRACT Chapter 1 is a brief summary of the history of gold in medicine from ancient times until today. It also explains the physical-chemical properties that make gold such a unique metal and introduces its fundamental role in organometallic chemistry. In addition, we made a summary of some of the main applications of gold(I), in medicine and catalysis. The use of gold in medicine and the possible mechanisms of action of the metal complexes currently used in therapy are introduced and subsequently the role played by gold(I) and gold(III) in homogeneous catalysis and asymmetric catalysis is developed. In chapter 2, the synthesis of various N-acyclic gold(I) carbenes is developed. Multicomponent processes (MCR), which have high importance in the development of new drugs mainly by their atomic efficiency have been tested with gold(I) NAC complexes. These complexes catalyze the formation of different propargylamines, which constitute very versatile building blocks for the synthesis of drug precursors, through an A3 coupling reaction; as well as the synthesis of various indolizines, one of the most important N-fused heterocyclic skeletons found in a variety of active biological compounds. In the same chapter the synthesis of biscarbenes and thiolate complexes based on DNA and pyrimidine bases of sugar derivatives has been carried out. These derivatives have a good internalization and cellular distribution. The cytotoxic activity and selectivity of all these NAC-gold (I) carbenes as well as the type of cell death induced have been studied. In Chapter 3 the synthesis of various silver(I) and gold(I) N-heterocyclic carbenes, bearing phosphonium and thiolate fragments, are described. The intention is the synthesis of new complexes with higher activity at lower concentrations, thus minimizing unwanted side-effects. In addition, cytotoxic activity studies were conducted against different cell lines, obtaining very interesting results. Finally, the preparation of gold compounds with NHC ligands substituted by triazole groups, obtained by clicking reactions, is also collected.