Stephen James Lippard (born October 12, 1940) is the Arthur Amos Noyes Emeritus Professor of Chemistry at the Massachusetts Institute of Technology. He is considered one of the founders of bioinorganic chemistry, studying the interactions of nonliving substances such as metals with biological systems. He is also considered a founder of metalloneurochemistry, the study of metal ions and their effects in the brain and nervous system. He has done pioneering work in understanding protein structure and synthesis, the enzymatic functions of methane monooxygenase (MMO), and the mechanisms of cisplatin anticancer drugs. His work has applications for the treatment of cancer, for bioremediation of the environment, and for the development of synthetic methanol-based fuels.
Education Lippard was born in Pittsburgh, Pennsylvania, where he graduated from Taylor Allderdice High School in 1958. He earned his bachelor's degree from Haverford College in 1962. Originally interested in attending medical school, a talk on medicinal chemistry by visiting chemist Francis P.J. Dwyer inspired Lippard to focus on inorganic chemistry for his Ph.D. Lippard worked with F. Albert Cotton at MIT on rhenium oxo complexes and clusters. He completed the thesis Chemistry of the bromorhenates, receiving his Ph.D. from MIT in 1965.
Career Lippard joined the faculty of Columbia University in 1966 as an assistant professor. He was promoted to associate professor with tenure in 1969 and full Professor in 1972. In 1983, Lippard returned to MIT as a professor of chemistry. He has held the Arthur Amos Noyes Professorship of Chemistry at MIT since 1989. He and his wife Judy were housemasters at MIT's MacGregor House from 1991 to 1995. Lippard served as the head of the MIT chemistry department from 1995 to 2005. He is recognized for his scientific work and for his work with students, having mentored more than 100 PhDs. His students are active in a wide range of areas, in part because "He delivers a strong message that you need to go to the frontier of science and pick interesting problems." Forty percent of his graduate students have been women, who he gives "high-risk, high-reward projects". Lippard has co-authored over 900 scholarly and professional articles, and co-authored the textbook Principles of Bioinorganic Chemistry (1994) with Jeremy Berg. He edited the book series Progress in Inorganic Chemistry from Volume 11 to 40. He was an Associate Editor of the journal Inorganic Chemistry from 1983 to 1989, and an Associate Editor of the Journal of the American Chemical Society from 1989 to 2013, as well as serving on the editorial boards of numerous other journals.
Research Lippard's research activities are at the interface of biology and inorganic chemistry. Lippard focuses on understanding the physical and structural properties of metal complexes, their synthesis and reactions, and the involvement of metal ions in biological systems. The formation and breaking of molecular bonds underlie many biochemical transformations. Purely inorganic substances such as iron are often required in essential organic reactions, e.g. oxygen binding in the hemoglobin family. Lippard attempts to better understand the role of metal complexes in the physiology and pathology of existing biological systems, and to identify possible applications of metal ions in medical treatment. He has made major contributions in a number of areas, including the development of platinum-based anticancer drugs such as the cisplatin family. Another area of interest is the structure and function of methane and enzymes that consume greenhouse gas hydrocarbons. In metalloneurochemistry, he studies the molecular activity of metal ions in the brain and develops optical and MRI sensors for binding, tracking, and measuring metal ions as they interact with neurotransmitters and other biological signaling agents.
Cisplatin
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.
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