Cisplatin is one of the most frequently used chemotherapy medications for many forms of cancer.
 It was discovered in the 1960s by Barnett Rosenberg, but its mechanism of action was not understood.

Early work in Lippard's lab on the interaction of metal complexes with nucleic acids led to the discovery of the first metallo-intercalators and eventually to the understanding of the mechanisms of cisplatin.

Lippard and his students examined sequences of DNA and RNA and incorporated  sulfur atoms into the sugar-phosphate backbone, where they selectively bound mercury or platinum complexes to specific positions.
Karen Jennette's discovery that sterically encumbered platinum complexes were more successful in binding to sulfur atoms in tRNA than mercury salts led researchers to propose that the platinum complexes intercalated between the double-stranded RNA's base pairs.
It was the first experimental demonstration to show a metal complex binding to DNA by intercalation: platinum terpyridine complexes inserted between the DNA base pairs and unwound the double helix.
 Using fiber X-ray diffraction, Peter Bond and others were able to display the intercalated platinum complex and to confirm predictions that the spacing of intercalators in DNA base pairs would follow the neighbor exclusion rule.

This established the groundwork for subsequent work on intercalative binding.
Jacqueline Barton and others have used electron micrography to show that the covalent binding of platinum complexes changes the supercoiling of the DNA, "bending and unwinding" the double helix.


Further experiments have explored the mechanisms through which platinum drugs bind their biological targets and led to insights into their anticancer activity.
Important results include the identification of an intrastrand d(pGpG) cross-link as the major adduct on platinated single-stranded DNA, identification of the major adduct on double-stranded DNA, the binding of high-mobility-group proteins to platinated DNA cross-links.
Using X-ray crystallography and other techniques,  Lippard and his coworkers have examined the mechanisms involved in binding cisplatin to DNA fragments, to better understand how cisplatin invades tumor cells and interferes with their activity.
 The interaction of Cisplatin and DNA results in the formation of DNA-DNA interstrand and intrastrand crosslinks which block DNA replication and transcription mechanisms.

As well as the intrastrand cross links created by cisplatin, monofunctional metal complexes may suggest possible cancer treatments.

A related line of research in Lippard's laboratory involves platinum blues.
Jacqueline Barton was the first person to synthesize and structurally characterize a crystalline platinum blue, pyridone blue.
Since then, extensive research has been done on the structure, properties, and reactions of such complexes.
Cisplatin is one of the most frequently used chemotherapy medications for many forms of cancer.  It was discovered in the 1960s by Barnett Rosenberg, but its mechanism of action was not understood.
Early work in Lippard's lab on the interaction of metal complexes with nucleic acids led to the discovery of the first metallo-intercalators and eventually to the understanding of the mechanisms of cisplatin. 
Lippard and his students examined sequences of DNA and RNA and incorporated  sulfur atoms into the sugar-phosphate backbone, where they selectively bound mercury or platinum complexes to specific positions. Karen Jennette's discovery that sterically encumbered platinum complexes were more successful in binding to sulfur atoms in tRNA than mercury salts led researchers to propose that the platinum complexes intercalated between the double-stranded RNA's base pairs. It was the first experimental demonstration to show a metal complex binding to DNA by intercalation: platinum terpyridine complexes inserted between the DNA base pairs and unwound the double helix.  Using fiber X-ray diffraction, Peter Bond and others were able to display the intercalated platinum complex and to confirm predictions that the spacing of intercalators in DNA base pairs would follow the neighbor exclusion rule.
This established the groundwork for subsequent work on intercalative binding. Jacqueline Barton and others have used electron micrography to show that the covalent binding of platinum complexes changes the supercoiling of the DNA, "bending and unwinding" the double helix.

Further experiments have explored the mechanisms through which platinum drugs bind their biological targets and led to insights into their anticancer activity. Important results include the identification of an intrastrand d(pGpG) cross-link as the major adduct on platinated single-stranded DNA, identification of the major adduct on double-stranded DNA, the binding of high-mobility-group proteins to platinated DNA cross-links. Using X-ray crystallography and other techniques,  Lippard and his coworkers have examined the mechanisms involved in binding cisplatin to DNA fragments, to better understand how cisplatin invades tumor cells and interferes with their activity.  The interaction of Cisplatin and DNA results in the formation of DNA-DNA interstrand and intrastrand crosslinks which block DNA replication and transcription mechanisms.
As well as the intrastrand cross links created by cisplatin, monofunctional metal complexes may suggest possible cancer treatments.
A related line of research in Lippard's laboratory involves platinum blues. Jacqueline Barton was the first person to synthesize and structurally characterize a crystalline platinum blue, pyridone blue. Since then, extensive research has been done on the structure, properties, and reactions of such complexes.
Stephen J. Lippard