Synthetic routes and chemical structural analysis for guiding the strategies on new Pt(ii) metallodrug design

Abstract

Metals in medicine is a distinct and mature field of investigation. Its progress in recent times cannot be denied, as it provides opportunities to advance our knowledge of the properties, speciation, reactivity and biological effects of metals in a medicinal context. The development of novel Pt(II) compounds to combat cancer continues to make valuable contributions but it has not yet achieved a complete cure. The chemistry of this field is basic for drug design improvements and our analysis of the chemical procedures is a practical tool for achieving effective Pt(II) anticancer drugs. We present chemical approaches in a manner that can be used to strategically plot new synthetic routes choosing right pathways. Clarifying the chemical challenge will help the scientific community to be aware of the ease and/or difficulty of the procedure before and after further studies, such as speciation, reactivity and biological action which are also very arduous and costly. The work provides information to tackle many challenges in chemistry, combining the knowledge on the Pt(II) reagent preparation together with the reactivity of the biological units used in the Pt(II) drug design. We discuss and include the description of the chemical reactions, the importance of multiple steps and the right order of such reactions to achieve the final drugs, analyzing the coordination principles as well as the organic and organometallic basis. This thorough study of the routes helps to detect the simpler or more complicated reactivity and will serve to improve the synthesis performance with possible post-modifications.