Figure 1.

Impact of hydrolysis rate (aquation reaction kinetics) on tissue distribution and toxicity. Tissue distribution of unchanged platinum drug is mainly determined by the lipophilicity or hydrophobicity of its carrier and leaving group, respectively. After substitution with water, the positively charged reactive compound present in plasma (and potentially bound to plasma proteins) can hardly penetrate tissue barriers. In contrast, reactive compounds present in the tissue will lead to toxicity.