How does the anticancer agent cisplatin work?
(The molcule of Cisplatin is made up of a central platinum atom covalently bonded to two ammonia (NH3) groups and two chlorine (Cl) atoms and has a square planar structure). Cisplatin works as an anticancer agent by bonding to adjacent guanine bases present in strands of human DNA, which distorts the DNA structure and thus prevents replication of the cell and initiates cell death. When inside the cell, cisplatin is slowly hydrolysed and one chlorine atom in cisplatin is replaced by water to form cis-[PtCl(NH3)2(H2O)]+. The water molcule bound to the platinum is then replaced, via ligand substitution, by Guanine, due to the lone pair electrons on the N7 nitrogen making guanine a better ligand than water, as it can form stronger co-ordinate bonds than water (note: electrons on nitrogen are less strongly held than the electrons in the more electro-negative oxygen atoms, therefore in general, nitrogen atoms will donate their electrons for dative covalent bond formation more readily). The displacement process then repeats with the other chlorine atom and another guanine molecule, resulting in a DNA strand with a distorted, irrepairable structure, resulting in prevention of DNA/cell replication and programmed cell death (known as apoptosis). Typically, cisplatin affects cancerous cells more than healthy cells due to the increased replication rate of cancerous cells - however cisplatin can also cause cell death in healthy cells, particularly naturally fast-replicating cells, such as hair follicles.
