Kurt W. Zilm

Professor of Chemistry and Chemical Engineering
Member of Yale faculty since 1982

E-mail: kurt.zilm@yale.edu
Web site: http://www.yale.edu/zilm

Research Research in our laboratory involves invention of new NMR methods and their application to important problems in chemistry and materials science. At present the main focus is on development of high-resolution solid state NMR techniques for probing the structure and physical chemistry of macromolecules in nanocrystalline form. One motivation for this work is the recognition that while the bulk of the 3-dimensional structural data for proteins and nucleic acids has been derived from crystalline samples in the solid state, there have been no widely applicable structure specific spectroscopic methods for probing chemistry in the same samples. With the resolution to observe individual amino acid residues in complex proteins, NMR methods are ideal for observing dynamics of individual side chains, the ionization state of an active site, or the interaction of individual residues with bound water molecules. By using NMR in the solid state, these types of studies can be directly correlated with crystallographic data. Another attractive feature of using solid state NMR methods is that the study of weakly bound ligands or lead compounds to receptors is facilitated by using solid state samples. As long as there is some specific affinity for a ligand, it is possible to fully populate a binding site in nanocrystalline samples. In solution phase this is generally not feasible unless a great excess of ligand is utilized as the required protein concentration needed to shift the dissociation equilibrium to the ligand bound state with a moderate kd values can be greater than that encountered in the solid. We are also developing methods for what we term solid state NMR nanocrystallography, an approach to using solid state NMR to determine high resolution 3D structures of proteins using crystals with dimensions the order of tens to hundreds of nanometers, far too small for most macromolecular X-ray crystallographic structure methods.

Members of the group currently design and construct new NMR instrumentation, invent new NMR pulse sequences, and work on refinement of the methods used for extracting structural parameters from NMR data. Applications of these new techniques being pursued include determination of tertiary structure of proteins which form small or poorly diffracting crystals such as most membrane proteins, probing water dynamics, and following the glass transition in proteins on a residue by residue basis. A very important tool for this work is our 800 MHz solid state NMR spectrometer, which provides the sensitivity required to perform our experiments on samples of only 6 μl in volume. Additional areas of current interest include using solid state NMR to characterize polymorphic phases of important pharmaceuticals, study of organic and inorganic nanotubes by multinuclear high field NMR, and NMR of transition metal complexes, especially those involving tunneling hydride ligands.

Education
B.S. University of Utah, 1976
Ph.D. University of Utah, 1981
Postdoctoral study in Chemical Physics, University of California, Berkeley, 1982-83

Honors
IBM Postdoctoral Fellowship, 1982-83
Dreyfus Newly Appointed Young Faculty in Chemistry Award, 1983
Franz-Vögt Prize of the Justus-Liebig University, Giessen, FDR, 1987
Dreyfus Teacher-Scholar Award, 1988

Recent Publications
R.W. Martin & K.W. Zilm. Variable Temperature System Using Vortex Tube Cooling and Fiber Optic Temperature Measurement for Low Temperature Magic Angle Spinning NMR. J. Magn. Reson. 2004, 168, 202-209.

C.R. Morcombe, V. Gaponenko, R.A. Byrd, & K.W. Zilm. Diluting Abundant Spins by Isotope Edited Radio Frequency Field Assisted Diffusion. J. Am. Chem. Soc. 2004, 126, 7196-7197.

E.K. Paulson, R.W. Martin, & K.W. Zilm. RF Homogeneity in High Field Solid State NMR Probes. J. Magn. Reson. 2004, 171, 314-323.

E.K. Paulson & K.W. Zilm. Linear Phase Correction of Folded Multidimensional NMR Data by Zero Inter filling. J. Magn. Reson. 2004, 168, 217-219.

E.K. Morcombe, V. Gaponenko, R.A. Byrd, K.W. Zilm. 13C CPMAS Spectroscopy of Deuterated Proteins: CP Dynamics, Line Shapes and T1 Relaxation. J. Am. Chem. Soc. 2005, 12, 397-404.