Prior to the serendipitous discovery of the first cisplatin anti-cancer complex in 1965 by Dr Barnett Rosenburg after studying unusual bacterial growth patterns, men with testicular cancer had limited medical options available to them with most of cases being fatal [1]. Results have now shown that, with an early diagnosis, over a ten-year age-standardised period net survival rate has increased from 69% in 1972, to 98% in 2011, in England and Wales [2]. Despite this breakthrough, cisplatin is incredibly toxic and can lead to adverse side effects and cancer resistance with respect to the compound, so the distinction between a therapeutic and toxic dosage has, historically, been a prevalent issue. Using cisplatin as the reference compound, non-classical
…show more content…
This is due to the small chloride ion concentration (15mM) compared to blood (0.1M) in the cytoplasm, the activation of the arsenoplatin drug occurs by hydrolysis with the formation of a partially aquated Pt complex. The monofunctional species in turn interacts with the DNA base. To establish how the structure and therefore the reactions of arsenoplatin differ from other platinum complexes we need to look at many key factors. Primarily, The Pt centre in the arsenoplatin adopts a square planar geometry with As,Cl and two nitrogen donors in a trans position. The trans effect on the As induces shorter bond length between the water ligand and the AsPt centre within the hydrolysis reaction hence the chloride substitution is easier with a lower activation barrier than cisplatin. As shown in figure 1, the N1-C1, O1-C1 and the N2-C3/ O2-C3 are indicative of a high degree of delocalisation present in the chelate rings formed by bridging N,O acetylamido ligands. Additionally, the As–Pt bond is strong and As simultaneously acts Lewis base (As-Pt) and as a Lewis acid (O-As). This allows it to undergo rapid ligand exchange reactions at the Pt centre whilst maintaining its stereochemistry, preserving a high electron affinity and allowing most metal ions to straightforwardly polarize groups that are coordinated to them, thus facilitating their hydrolysis with the DNA.
This is due to the small chloride ion concentration (15mM) compared to blood (0.1M) in the cytoplasm, the activation of the arsenoplatin drug occurs by hydrolysis with the formation of a partially aquated Pt complex. The monofunctional species in turn interacts with the DNA base. To establish how the structure and therefore the reactions of arsenoplatin differ from other platinum complexes we need to look at many key factors. Primarily, The Pt centre in the arsenoplatin adopts a square planar geometry with As,Cl and two nitrogen donors in a trans position. The trans effect on the As induces shorter bond length between the water ligand and the AsPt centre within the hydrolysis reaction hence the chloride substitution is easier with a lower activation barrier than cisplatin. As shown in figure 1, the N1-C1, O1-C1 and the N2-C3/ O2-C3 are indicative of a high degree of delocalisation present in the chelate rings formed by bridging N,O acetylamido ligands. Additionally, the As–Pt bond is strong and As simultaneously acts Lewis base (As-Pt) and as a Lewis acid (O-As). This allows it to undergo rapid ligand exchange reactions at the Pt centre whilst maintaining its stereochemistry, preserving a high electron affinity and allowing most metal ions to straightforwardly polarize groups that are coordinated to them, thus facilitating their hydrolysis with the DNA.