Eckermann Research Group
Dr. Eckermann is interested in virtually all areas of chemistry and her main passion is bioinorganic chemistry. The singular goal of the Eckermann group is to use coordination chemistry to probe biological processes. The Eckermann research group typically consists of three to five intelligent, self-motivated and hard-working students focusing on the development of biologically active inorganic complexes and materials. Their current research addresses the following three areas:
- Design of ruthenium complexes that coordinate to and disrupt the structure of Aβ42 (the peptide implicated in Alzheimer’s disease)
- Development of anti-cancer ruthenium drugs with glucose tags for targeting cancer cells
- Doped hydroxyapatite nanoparticles for multimodal biomedical imaging.
These projects provide opportunities for students to master advanced synthetic techniques (organic and inorganic), biochemical assays and a wide variety of analytical instrumentation (NMR-, UV-visible-, IR- and Raman-spectroscopy, cyclic voltammetry, ICP-OES, SEM/EDS, XRD). After working at the interface of chemistry and biology, research students go on to graduate school in chemistry, healthcare fields or careers in industry. Applications from enthusiastic students are always welcome — contact Dr. Eckermann today if you are interested!
Transition Metal Disruptors of AB Oligomerization
Soluble oligomers of beta-amyloid (Aβ42) are implicated in the neurodegeneration of Alzheimer's Disease. The sequence of the peptide includes a hydrophobic region (residues 16-21), as well as residues that can coordinate to transition metal ions (His 6, 13, 14 and Met 35). One proposed mechanism of oligomerization begins with the hydrophobic region of the peptide. Therefore, we seek to probe the oligomerization mechanism using transition metal complexes with hydrophobic ligands that will:
- Coordinate to the His residues
- Interfere with the hydrophobic interactions between peptides
To this end, we have designed and synthesized ruthenium complexes that bind to imidazole (to mimic histidine), and have hydrophobic features. We have shown computationally and experimentally that these complexes bind to cyclodextrin, a model for studying hydrophobic interactions (see below, left). These complexes further undergo ligand exchange with 4-methyl imidazole (4MeIm), suggesting they will coordinate to the His residues of Aβ42.
Platinum-based chemotherapeutics are well known for targeting cancerous and somatic cells indiscriminately, while emerging ruthenium-based chemotherapeutics have diverse in vivo properties such as anti-metastatic behavior and lower overall cytotoxicity. To preserve these characteristics and improve selectivity by taking advantage of the Warburg effect, we are synthesizing glycoconjugated ruthenium complexes such as the dimer shown here. Complexes are tested in cancer cell lines such as A2780, MCF7, and HeLa, and the effects on cell viability are quantified using the alamarBlue® assay. Fluorescence microscopy images are obtained to show effects on the cell morphology. We use computational modeling to assist the design of second-generation glucose-modified ruthenium drugs.
Multimodal Hydroxyapatite Nanoparticles
Hydroxyapatite is a biocompatible material that is readily modified as a scaffold for multimodal imaging. Specifically, we seek to combine the excellent spatial resolution of MRI with the sensitivity of PET in a nanoparticle agent that can be specifically targeted within a biological system to an area of interest (ie, a tumor). We use three approaches to build these multimodal agents:
- Particles can be doped with PET- and MRI-active ions (e.g., iron or gadolinium) during synthesis
- PET- and MRI-active agents can be attached to the particle surface through covalent or electrostatic interactions
- Core-shell nanoparticles with MR-active iron oxide centers
We have demonstrated that sodium alendronate can be used to provide robust functionality for the surface modification of hydroxyapatite particles. Further, we have found that strontium leaches quickly out of the hydroxyapatite lattice, suggesting these particles could be used as a delivery vehicle for osteoporosis treatments. Our current work is focused on tuning the properties of core-shell platforms for theranostic applications.
A. Paul Schaap Science Center35 East 12th StreetRoom 3101Holland, MI 49423