Research Interest(s):

Inorganic and Bioinorganic Chemistry

Research in my group is focused on the roles of transition metal ions in biology. Of particular interest are proteins and enzymes involved in biological CO, NO, and O₂ sensing (Figures 1 & 2), activation of O₂, heme transport in bacterial pathogens (Figures 3 & 4), and metal-dependent proteolysis (Figures 5 & 6). We bring a variety of chemical, spectroscopic, and computational methods to bear on questions of the interplay between structure, dynamics, and function of metalloproteins. Chemical methods include synthesis and characterization of model complexes, studies of reaction rates and mechanism, and protein expression and purification. Among the physical methods are resonance Raman, steady-state and transient UV-visible absorbance, circular dichroism, NMR, EPR, and crystallography. We use computational methods based on density functional theory and molecular mechanics force fields to gain insight into structure, bonding and reactivity of metal-containing protein active sites.

Figure 1. Transient absorbance spectra used to determine rates of ligand rebinding to the heme and ligand-coupled conformational dynamics in O₂₆sensing protein, FixL.

Figure 2. HOMO of [Fe(por)NO]+, showing the Fe-N and N-O antibonding character of the {FeNO}₆ moiety. We have shown that the behavior of these bonds is in contrast to the classical backbonding behavior in which the Fe-X and X-O bond strengths vary inversely. The FeNO antibonding character of the HOMO in these {FeNO}₆ porphyrinates causes the Fe-N and N-O bond strengths to vary directly in response to both intra- and intermolecular influences.

These efforts combine synthetic inorganic and organic chemistries for the production of new materials, along with the structural, electronic, and optical characterization of these materials via various physical and analytical methods. In addition, the Rasmussen group collaborates with researchers worldwide in the application of materials developed at NDSU to working photovoltaic devices, OLEDs, and NIR light detectors. As such, students working on these projects gain experience in organic, inorganic, and polymer synthesis, as well as additional experience with a variety of spectroscopic, electrochemical, crystallographic, and computational techniques. Via various collaborations, students can also gain experience with hands-on device fabrication.

Figure 3. Cartoon illustrating the heme uptake and intracellular transport steps in iron assimilation by the bacterial pathogen, Shigella dysenteriae. We are working to understand the molecular mechanisms by which heme is transferred between the proteins that comprise this pathway.

Figure 4. Resonance Raman spectra of the periplasmic heme binding protein, ShuT. Spectra of the wild type and Y94A mutants are shown. These spectra provide part of the evidence for assignment of the endogenous heme ligand, Tyr94.

Figure 5. X-ray crystal structure of [TpPh,MeZn(2−ImPr)]. The bidentate 2−ImPr‾ ligand is rendered in ball-and-stick format. This complex is a structural mimic of the active sites in zinc-dependent metalloproteases of the metzincin class. We are designing and testing novel zinc chelating groups that could be conjugated to larger molecules to make a new generation of metzincin inhibitors. Such chemotherapeutic agents could be valuable in treating a variety of diseases, including cardiovascular disease, stroke, cancers, and arthritis.

Figure 6. 500 MHz 1H NMR spectra tracking the titration of [TpPh,MeZnOH], a mimic of metzincin resting states, with HClO₄ in CD₃OD at 25 °C (middle and right panels). The left panel shows single-proton titration curves derived from the [H+] dependences of the 1Ha and 1Hc chemical shifts. Understanding the effects of acid-base interconversions on the NMR spectrum allows us to clearly identify the spectral changes associated with displacement of the hydroxide ligand by our zinc binding groups.

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