October 2002 Meeting Basolo Award Presentation

	Joint Meeting of the Northwestern University Department of Chemistry and the Chicago ACS Section

Date:  Friday, October 18, 2002

Background information about the Basolo Award

NOTE: The Basolo Medal Lecture will be held at 4:30 P.M. - 5:45 P.M. at Northwestern University.
--- The Medalist Lecture is open to the public and admission is free to all those wishing to attend. ---

Northwestern University
Technological Institute
2145 Sheridan Road
Evanston, IL
Lecture Room 3

Abstract:     The interface between inorganic and biological chemistry is broad and expanding. Metal ions are extensively applied in diagnostic and therapeutic medicine. The simple coordination compound cis-diamminedichloroplatinum(II), also known as cisplatin, has contributed significantly to the management of testicular cancer. This and related platinum anticancer drugs kill cancer cells through a multifactorial mechanism. The first step is activation to facilitate DNA binding. Structures of the major platinum-DNA adduct reveal distortions of the double helix that trigger the interaction of proteins involved in gene activation. Inhibition of the key cellular processes of transcription and nucleotide excision repair ensues. These processes are being investigated using site-specifically platinated DNA in a nucleosome. A means of applying this information has afforded a new approach to treat ovarian cancer that is the basis for a clinical trial. Metal ions are also key components of enzymes. In methanotrophic bacteria, which use methane as their sole source of carbon and energy, a hydroxylase enzyme (MMOH) housing a carboxylate-bridged non-heme diiron unit activates dioxygen for the selective conversion of methane into methanol. This remarkable reaction proceeds in a stepwise fashion, the details of which have been delineated through structural studies of the enzyme and its partner proteins required for activity, mechanistic studies of intermediates, and experimental and theoretical analyses of the C-H bond activation step. The transition state involves a bound radical that evolves products through both concerted insertion and recoil/rebound steps. Analogs of the active site have been synthesized that afford insight into the structures and chemistry of MMOH. Neurochemistry is similarly replete with inorganic ions essential for function. New fluorescent sensors for zinc and nitric oxide have been obtained that have the potential to map neural networks in the hippocampus, the center of learning and memory. Biography:     Professor Lippard was born in Pittsburgh, PA, was an undergraduate at Haverford College (B.A., 1962) and completed his graduate work at M.I.T., receiving the Ph.D. in 1965. After a postdoctoral year as an NSF Fellow at M.I.T., he joined the faculty of Columbia University as an Assistant Professor in 1966, was appointed to Associate Professor with tenure in 1969 and to full Professor in 1972. He returned to M.I.T. as Professor of Chemistry in 1983, was appointed Arthur Amos Noyes Professor in 1989, and Head of the Chemistry Department in 1995. Professor Lippard has received many fellowships and prizes, including the Henry J. Albert Award of the International Precious Metals Institute for his work on platinum metals and their interactions with nucleic acids, election as Fellow of the American Academy of Arts and Sciences, the ACS Award in Inorganic Chemistry sponsored by Monsanto Company, the Remsen Award sponsored by the Maryland Section of the ACS, an Alexander von Humboldt Senior U.S. Scientist Award, election to the National Academy of Sciences, election to the National Institute of Medicine, the John C. Bailar, Jr. Metal of the University of Illinois, the ACS Award for Distinguished Service in Inorganic Chemistry sponsored by Mallinckrodt Company, the William H. Nichols Metal sponsored by the New York Section of the ACS, an Honorary D.Sc. Degree from Texas A&M University, an honorary membership in the Italian Chemical Society, scientific membership in the Max-Planck-Gesellschaft, an honorary D.Sc. degree from Haverford College, and the Richards Metal of the Northeast Section of the ACS. He is author or co-author of over 550 articles in professional and scholarly journals, has written or edited two textbooks, and holds several U.S. and foreign patents. He has published a book with Jeremy Berg entitled "Principles of Bioinorganic Chemistry." Dr. Lippard's research activities span the fields of inorganic and biological chemistry. Included are structural and mechanistic studies of platinum anticancer drugs and of methane monooxygenase, the synthesis of carboxylate-bridged dimetallic complexes as models for redox-active enzymes and metallohydrolases, and probes for the neurochemical function of zinc, calcium and nitric oxide. Also among his many activities he is an avid harpsichordist, an early morning jogger, and occasional horseback rider.