Metallo-β-lactamases (MBLs) are Zn(II)-containing enzymes produced by bacteria that inactivate all b-lactam containing antibiotics, including the carbapenems, which are antibiotics of last resort. While the MBLs have been studied for over 50 years, there are no clinical inhibitors for these enzymes. Therefore, there are few antibiotics available to treat bacterial infections caused by bacteria that produce a MBL. To address this problem, a multi-institution team of synthetic organic chemists (UC San Diego), medicinal chemists (UT Austin), microbiologists and MD’s (Case Western and the Cleveland VA), and structural biologists/biochemists (Miami University) teamed together to identify and develop new potential leads. In the seminar, recent results on a new inhibitor scaffold will be presented, along with biophysical studies on several other recently reported compounds in the literature.

Abstract:

Chemistry has always been an experimental science, but its guiding principles have come from the realm of physics since the discovery of the nucleus, electrons, and the quantum mechanics that rules them.  The field of quantum chemistry has matured to the point where computations can assist in understanding results form the laboratory, or even in suggesting future experimental work.  To obtain results of sufficient accuracy, the theoretical chemist must use a large basis set to expand the orbitals and a sufficiently sophisticated many-electron wavefunction.  However, when a heavy element is involved, a third complication arises, namely relativity.  This seminar will present a computational complement to results obtained in the Yang Laboratory at the University of Kentucky for a Cerium containing molecule.  The talk is intended to teach students the connection between the Schrodinger equation and the relativistic Dirac equation.  The correct physics of the latter can be approximated in a normal quantum chemistry program solving the former equation by modification of one electron integrals.  The presentation of relativistic quantum mechanics will be qualitative - no prior understanding of Einstein is necessary!