Janet Del Bene
Department of Chemistry, Youngstown State University
Two-bond Spin-spin Coupling Constants (2hJx-y) across X-H-Y Hydrogen Bonds: Some Fundamental Questions




Connie Hall
Director, Cell and Tissue Engineering Track, Pritzker Institute of Biomedical Science & Engineering
Biomedical Engineering and the Problem of Thrombosis: The Importance of Transport Phenomena




Sabeeha Merchant
Department of Chemistry and Biochemistry University of California, Los Angeles
Layers of Gene Regulation to Handle Life without Copper




Emma R. Parmee
Merck, Co., Inc.
A New Approach to the Treatment of Type II Diabetes: From Lead Discovery to Clinical Candidate




Birgitta Whaley
Department of Chemistry, University of California, Berkeley
Molecules in Helium and Hydrogen Clusters: An Ultra-cold Nnanolaboratory for Solvation Studies

Special Presentations

Francine Berman, San Diego Supercomputer Center, UC San Diego
Marjorie Caserio, UC San Diego
Chancellor Marye Anne Fox, UC San Diego
Irene Lombardo, National Science Foundation

Session Chairs

Kim Baldridge, UZH and San Diego Supercomputer Center
Ivana Adamovic
Jamie Rintelman
Heather Netzloff
Maryann Martone
Laura Brovold


10th Annual Maria Goeppert-Mayer Interdisciplinary Symposium at the San Diego Supercomputer Center on the UCSD campus.

This 10th anniversary celebration is a special event that commemorates both the inspirational career of Maria Goeppert-Mayer as well the remarkable women who have participated in this symposium since 1996.

Two-bond Spin-spin Coupling Constants (2hJx-y) across X-H-Y Hydrogen Bonds: Some Fundamental Questions

Investigations of spin-spin coupling constants (2hJx-y) across X-H-Y hydrogen bonds 2h constitute a relatively new and exciting area of theoretical and experimental research. Despite the tremendous progress that has been made in a short period of time, there remain
many fundamental questions that need to be addressed. Among these are the following:

1) Is it possible to predict the signs of two-bond spin-spin coupling constants (2hJx-y) across 2h X-H-Y hydrogen bonds?

2) What determines the sign of 2hJx-y

3) Does the measurement of a two-bond coupling constant prove that the hydrogen bond is covalent?

4) What role does the proton play in coupling across hydrogen bonds?

Systematic studies of two-bond coupling constants for series of complexes stabilized by C-H-N, N-H-N, O-H-N, F-H-N, C-H-O, N-H-O, O-H-O, and F-H-O hydrogen bonds have been carried out using the ab initio equation-of-motion coupled cluster singles and doubles (EOM-CCSD) method. The results of these studies are used to provide some answers to these questions.

Dr. Janet E. Del Bene is Professor Emeritus of Chemistry at Youngstown State University, and Adjunct Professor at the Quantum Theory Project, University of Florida. She received her Ph.D. in 1968 from the University of Cincinnati, and did postdoctoral work at the Theoretical Chemistry Institute at the University of Wisconsin, and at Mellon Institute with Dr. John A. Pople, prior to joining the faculty of Youngstown State University. The theme of her research has been ab initio quantum chemical studies of hydrogen bonding. Recent work has focused on anharmonicity and matrix effects on the IR spectra of hydrogen-bonded complexes, and on two-bond NMR spin-spin coupling constants across hydrogen bonds. Dr. Del Bene is a Fellow of the American Association for the Advancement of Science, and was granted the first CERFnet Award for Excellence in Networked Applications in 1991. She recently received a Two-Year Extension for Special Creativity to her NSF grant, a BBVA Visiting Fellowship at the Universidad Autónoma de Madrid, and the triennial National Honorary Member Award for an Outstanding Women Chemist from Iota Sigma Pi in 2002. In addition to her research, Dr. Del Bene also enjoys photography, music, and golf.


Biomedical Engineering and the Problem of Thrombosis: The Importance of Transport Phenomena
The application of fluid mechanics and mass transport theory to the analysis of the processes of thrombosis and hemostasis has contributed significantly to the current mechanistic understanding of these areas. Both physical and chemical factors can influence the activity of platelets and coagulation factors responsible for the formation of thrombotic and hemostatic masses in the vicinity of an injured vessel or at the surface of a device implanted in contact with blood. Studies performed in in vitro shear devices indicate that physical factors alone can induce platelet aggregation and the release of procoagulant microparticles from platelets or from the cells in the vascular wall. The physical considerations which appear to be important for the local activation of hemostatic (physiologic) or thrombotic (pathologic) mechanisms appear to be related to the magnitude of the shear rate/stress, the duration of the applied physical force, and the local geometry. Blood flow alone has multiple effects on platelet and coagulation processes. It has been well established that at physiologically encountered shear conditions, local increases in shear rate enhance platelet attachment to the vessel wall and the growth of platelet aggregates. In contrast, increases in local shear conditions inhibit the production of fibrin (the end product of coagulation). Shear stress is also implicated in the enhancement of the procoagulant activity of vascular cells. The application of in vitro flow devices and computational fluid dynamics continue to increase our understanding of these complicated processes and the modulating effects of physical forces.

Connie Hall received her B.S. and M.S. in bioengineering from UCSD. She worked in the bioengineering department for the next two years followed by one year at Corvas International, a start-up pharmaceutical company where she began her work in the area of thrombosis. In 1991 she began her Ph.D. work in the Department of Biomedical Engineering at the University of Memphis. Her research advisor, Vincent Turitto, D.Engr.Sci, contributed significantly to the first studies on transport phenomena and thrombosis. She completed her Ph.D. and an NIH research service award at the Univ. Of Memphis prior to moving to the Pritzker Institute at the Illinois Institute of Technology in Chicago. She is currently an assistant professor, the undergraduate studies coordinator in the Department of Biomedical Engineering and the Cell and Tissue Research Track Director in the Pritzker Institute of Biomedical Science and Engineering.


Layers of Gene Regulation to Handle Life without Copper
Copper is an essential micronutrient because of its role in enzymes that catalyze reactions involving oxygen or redox chemistry. We have developed Chlamydomonas reinhardtii, a eukaryotic alga amenable to molecular and genetic experimental approaches, as a superb system for studying copper homeostasis in the context of nutritional deficiency. Our research in this area led to the discovery of “back up” copper-independent metabolic routes in copper deficient cells that compensate for the loss of function of prominent cuproproteins. The prototypical example is the replacement of the blue copper protein plastocyanin in photosynthetic electron transfer by a heme protein, cytochrome c6. The reciprocal copper-responsive expression of plastocyanin in copper-replete cells vs. cytochrome c6 in copper-deficient cells is effected through a novel metalloregulator, called Crr1, which, in –Cu cells, activates transcription of CYC6 through copper response elements (CuREs) and induces degradation of apoplastocyanin. Crr1 regulates also a number of other targets including copper uptake components, enzymes in the tetrapyrrole biosynthetic pathway, and a back up for the copper-requiring ferroxidase, Fox1, that functions in iron assimilation. These metabolic adaptations allow the organism to grow in severely copper-deficient medium (1- 3 nM). In this situation, copper is allocated preferentially to cytochrome oxidase for which there is no good copper-independent back up over plastocyanin or the ferroxidases. Furthermore, as a culture grows and becomes progressively more copper-deficient, copper is scavenged from holoplastocyanin to maintain cytochrome oxidase. The initial hierarchical allocation is controlled by copper-independent metabolic regulation while the re-allocation depends on regulated degradation of plastocyanin in copper-deficient cells.

Sabeeha Merchant (website) was born and educated through high school in a small school for girls in Bombay, India. At the age of 12, in 9th grade, teachers assigned her to the science classes (which had more space) because aptitude tests indicated aptitude for both science and humanities, but she studied only chemistry, physics and mathematics for her O-level equivalent examinations because biology, with its frog and cockroach dissections, was unappealing. Ms. Merchant entered St. Xavier’s College of Bombay University as one of five female Chemistry majors in a class of over 300 students. A year later, possibly because of her lackadaisical attitude to her studies, her mother moved her to Whitewater, Wisconsin, to pursue an undergraduate education in Chemistry. Ms. Merchant changed her major to Molecular Biology because it gave her an excuse to leave small-town Whitewater for Madison. She undertook undergraduate research with Prof. Glenn Chambliss on modification of transcription patterns in B. subtilis upon phage infection and upon graduating summa cum laude joined the group of Prof. Henry Lardy, initially as a secretary (she was hired because she could spell mitochondria) and librarian, and later as a technician where she worked on glycolytic metabolism. Prof. Lardy encouraged her to consider graduate school and after visiting a number of distinguished institutions, she chose to remain at the University of Wisconsin because of the comfortable environment. Ms. Merchant joined the group of Prof. Bruce Selman and studied the aspects of the biogenesis of the chloroplast ATP synthase for her Ph.D. thesis. Her most notable discovery was to resolve a long-standing controversy concerning the subunit stoichiometry of the enzyme, which demonstrated the degree of structural conservation between the photosynthetic and mitochondrial enzymes. From Wisconsin, Sabeeha Merchant moved to Harvard University to learn molecular biology as a post-doctoral scholar on an NIH fellowship. She joined the group of Lawrence Bogorad initially to try to discover wave-length specific photoreceptors involved in the phenomenon of complementary chromatic adaptation in cyanobacteria, but after the laboratory was destroyed by fire, she developed the project that she continues in her own laboratory today. Specifically, she asked the question how Chlamydomonas cells survive copper deficiency when they clearly do copper proteins for metabolism. Results from the Merchant group have led to the elucidation of some fundamental concepts on trace element metabolism, including the discovery of “back up” copper-independent pathways that function only in copper deficiency and the demonstration of hierarchical distribution of a limiting nutrient to particular enzymes based on the importance of the enzyme for survival. Sabeeha Merchant joined the UCLA faculty in 1987 as an Assistant Professor of Biochemistry in the Department of Chemistry and Biochemistry and is presently a Professor in that department and has administrative responsibility as the Chair of the Inter-departmental Molecular Biology Ph.D. program and Acting Director of the Molecular Biology Institute. The Merchant group studies micronutrient homeostasis in Chlamydomonas, cytochrome c biogenesis in chloroplast, and aspects of chlorophyll biosynthesis. Her contributions on studies of metal nutrition and tetrapyrrole metabolism have been recognized by various awards including a Searle Scholar Award, an NIH Career Development Award, and a Guggenheim Fellowship, and her research is funded by the US Department of Agriculture, the National Institutes of Health, and the Department of Energy.


New Approach to the Treatment of Type II Diabetes: From Lead Discovery to Clinical Candidate
Inhibition of dipeptidyl peptidase IV (DPP-IV), a proline specific serine dipeptidase, is a novel therapeutic approach to the treatment of type 2 diabetes. DPP-IV rapidly cleaves the active form of the incretin hormone glucagon-like peptide 1 (GLP-1) to its inactive form and is thought to be the primary enzyme responsible for this hydrolysis. GLP-1 plays an important role in glucose-dependent insulin biosynthesis and secretion in humans. Infusion of GLP-1 has been shown to normalize both postprandial and fasting glucose levels in diabetics. Inhibitors of DPP-IV will significantly reduce inactivation of GLP-1 leading to an increase in circulating levels of the active form of the hormone and thus act as indirect stimulators of insulin secretion.

Importantly, in contrast to many current therapies for type 2 diabetes, this mechanism potentially carries with it only a low risk of hypoglycemia since GLP-1 stimulates insulin release solely in the presence of elevated plasma glucose levels. Other possible advantages of DPP-IV inhibitors as a treatment for diabetes include the fact that no weight gain is anticipated and there are potential long-term beneficial effects on pancreatic beta cell function.

Thus, there is much interest in the pharmaceutical industry in developing small molecule inhibitors of DPP-IV. This presentation will describe the discovery of novel DPP-IV inhibitors at Merck Research Laboratories and discuss the importance of a high level of selectivity for DPP-IV in the preparation of safe, well-tolerated compounds. These studies resulted in identification of clinical candidate MK-0431 which is currently in development for the treatment of Type II diabetes.

Emma Parmee was born in the U.K. and obtained her B.A. and D. Phil degrees in chemistry from Oxford University. Her post graduate research with Prof. E.J. Thomas centered on the total synthesis of milbemycin E, a macrolide natural product. In 1990, Emma obtained a NATO Post-doctoral fellowship and moved across the Atlantic. She worked at MIT in the laboratories of Prof. S. Masamune investigating novel catalysts for the asymmetric aldol reaction. Emma joined Merck Research Labs in Rahway, N.J. in 1992, where she is currently a Director of Medicinal Chemistry. Her work at Merck has focused on the treatment of metabolic disorders such as obesity and diabetes. She and her husband spend their spare time with their children Paul and Annie, who at ages 7 and 3 and a half keep them very busy!


Molecules in Helium and Hydrogen Clusters: An Ultra-cold Nanolaboratory for Solvation Studies
I shall present recent theoretical work on nanoscale clusters of helium and hydrogen that shows the onset of nanoscale superfluid response at small cluster sizes and novel molecular phenomena resulting from coupling of an embedded molecule to a quantum fluid solvating environment. Zero and finite temperature quantum simulations, providing evidence for a transition from van der Waals type clusters at small numbers of helium or hydrogen molecules to true superfluid solvation around small molecules in doped clusters, will be presented. The nature of the coupling between an impurity molecule and the solvating superfluid will be discussed and shown to probe local and collective excitations of the quantum fluid, respectively. Finally, we present evidence for a superfluid state of molecular hydrogen within a solvated nanocluster.

K. Birgitta Whaley is a Professor in the Department of Chemistry at the University of California, Berkeley, where she has been a faculty member since 1986. Her research interests include theoretical chemical and quantum physics; quantum information and theory of quantum computation; dynamics of open quantum systems; theory of decoherence; quantum nanoscale systems, including helium droplets, hydrogen clusters, and semiconductor nanocrystals; nanoscale superfluidity; and electronic, optical, magneto-optical and spintronic properties of semiconductor nanostructures. She received her B.A. in Chemistry from Oxford University in 1978, was a Kennedy Fellow at Harvard University (1978–79), and then earned her Ph.D. in Chemical Physics from the University of Chicago in 1984. She has held research positions at the Hebrew University, Jerusalem and the Tel Aviv University. She became a Fellow of the American Physical Society in 2002, and has been the recipient of the Bergmann Award (1986), the A. P. Sloan Foundation Fellowship Award (1991–93), Alexander von Humboldt Senior Scientist appointments (1996–97; 2004), and a Miller Institute for Basic Research in Science Professor appointment at the University of California, Berkeley (2002–03). She has authored over 145 scientific papers on helium cluster dynamics and on quantum computation. Recent activities include: service on the International Advisory Committee of the Australian Research Council Special Research Centre for Quantum Computer Technology (2001–), member of the External Review Committee for the Physics (P) Division at the Los Alamos National Laboratory (2002–), proposer and co-organizer of the “U.S.-Australia Workshop on Solid-state and Optical Approaches to Quantum Information Science,” Sydney and Brisbane, Australia (January 2003), proposer and Vice-chair of the 1st Gordon Research Conference on Quantum Information Science (March 2003), and Chair of the 2nd Gordon Research Conference on Quantum Information Science (February 2004).