Roy Young Chemistry Graduate Scholarship
Adyn Melenbacher and Yihong Liu. Hosted by Prof. Martin Stillman and Prof. Lijia Liu. Adyn and Yihong have been awarded the Roy Young Chemistry Graduate Scholarship.
Adyn Melenbacher
Title: The advantages of electrospray ionization mass spectrometry in metallothionein research
Abstract: Metals are an essential nutrient. Human physiological chemistry uses a range of metals from sodium to molybdenum. At least 50% of all enzymes in the body require at least one metal ion to function. These are often redox active metals, i.e. Fe(II)/(III) or Cu(I)/(II). Zn(II), being a good Lewis acid, also makes a good cofactor for enzymes. Metals can also be used to tune the structural properties of proteins by crosslinking different parts of the protein. These metals, while essential, are only needed in trace amounts (i.e. ~2 g Zn(II) in a 70 kg human). Toxic chemistry can occur if the concentration and cellular locations of metals are not carefully controlled. As a result, the body systems to control cellular metal concentrations that involve many transporter, chaperone, and storage proteins.
The metallothionein (MT) protein is a key metal storage protein for Cu(I) and Zn(II). This protein contains 20 cysteines and has no defined structure, which gives it great flexibility in its ability to bind d10 metals. MT binds Cu(I) and Zn(II) in metal-thiolate clusters with various stoichiometries that can coexist in solution. So far, research in the Stillman Bioinorganic Lab has focused on the stable clusters, or “magic numbers” forming when Cu(I) or Zn(II) are added separately to the apo or unmetallated protein. However, MTs are expected to bind a mixture of Cu(I) and Zn(II) together in vivo and so the properties of mixed-metal Cu,Zn-MTs are of great interest.
Electrospray ionization mass spectrometry (ESI-MS) is an essential technique in the study of MTs since it allows for the detection of each of the many different multiple metallated MT species existing in equilibrium in the solution. However, due to the presence of multiple naturally abundant isotopes of Cu(I) and Zn(II), it is very difficult to unambiguously distinguish between mixtures of the two metals binding to MT. To overcome this problem, isotopically pure 63Cu(I) and 68Zn(II) were used in combination with simulated ESI-mass spectral data to identify the Cu:Zn ratios that result upon the addition of 63Cu(I) to 68Zn7-MT. The species that form were found to have characteristic emission and circular dichroism spectral properties. The concurrent measurement of the ESI-mass spectrum along with these spectroscopic measurements allowed for the identification of specific species giving rise to the spectral bands. This led to the novel discovery of a Cu5Zn5-MT and Cu6Zn4-MT species which previously could not be resolved from each other.
Bio: Adyn Melenbacher is a 4th year PhD student working with Dr. Martin Stillman. She has been working in his lab since the second year of her undergraduate degree. Throughout her graduate career she has held NSERC CGS-M and CGS-D scholarships. Adyn studies the Cu(I) metallation properties of the metal storage protein metallothionein. Her research is based on recombinantly expressing the protein in E. coli and analyzing its properties using electrospray ionization mass spectrometry, emission spectroscopy, circular dichroism spectroscopy, NMR spectroscopy, and X-ray absorption spectroscopy.
Her research on metallothionein has been published in four peer-reviewed articles. She has also collaborated with Dr. Joe Gilroy and his student which resulted in two publications on the emission properties of boron difluoride formazanate dyes. She collaborated with the group of Dr. Clotilde Policar in Paris resulting in a publication on a catalase mimic peptide. Adyn has presented her work at international conferences in France, Italy, Australia, and Japan. Adyn was also the recipient of a Michael
Smith Foreign Study Supplement which allowed her to spend two months in Cardiff, UK working with Dr. Peter Kille. She was involved with his project investigating the impact of metals on soil invertebrates.
Yihong Liu
Title: Magnesium Germanate-Based Persistent Luminescent Nanophosphors: Finding the Optimal Structure for Stronger, Longer-Lasting Luminescence
Abstract : Persistent luminescence (PersL) nanomaterials emitting near-infrared (NIR) light are particularly interesting in the biomedical field, as the emitted light allows deep tissue penetration and can maintain its luminescence for an extended period after removing the excitation source, which can eliminate interference from tissue autofluorescence. Mn2+-doped magnesium germanate (MGO:Mn) nanoparticles (NPs) emit within the first NIR region (~680 nm), making them promising candidates for use as a bioimaging probe. In this talk, I will discuss a sol-gel method for synthesizing MGO:Mn NPs, where multiple spectroscopic techniques were used to carefully study the influence of calcinating temperature on the site occupancy of Mn2+ and luminescence properties. To further optimize the material for bioimaging applications, we introduce Yb3+ as a second dopant in the MGO:Mn system, producing dual-emission at both the first NIR and second NIR windows. The NIR-II emission is further enhanced by the addition of Li+. Further, I will discuss the local structure around the light activator Mn2+. Towards the end of the talk, I will introduce a hydrothermal method for synthesizing MGO:Mn NPs with improved optical properties compared to the conventional sol-gel method, and some future potential applications will also be presented.
Reference
[1] Y. Liu, et al. “The role of Li+ and Yb3+ in modulating the electronic structure and luminescence of MgGeO3:Mn2+ nanoparticles”. Journal of Alloys and Compounds. 957 (2023) 170422.
[2] Y. Liu, et al. “The effect of annealing temperature on the site occupancy and the persistent luminescence of Mn2+-doped magnesium germanate”. Material Today Communications. 38 (2024) 108080.
Bio: Yihong obtained her BSc degree in Chemistry with distinction in 2022 at Western University. In her fourth year of undergraduate study, she joined Dr. Lijia Liu’s research group as a volunteer and contributed to developing a calcium phosphate coating on titanium dioxide nanotubes. After completing her undergraduate studies, she stayed in the Liu group as an MSc candidate and held the Christian Sivertz Scholar position. During her MSc, she led a project on the synthesis of near-infrared persistent luminescence nanophosphors, specifically focusing on magnesium germanate-based nanophosphors. In October 2023, she transferred to the Ph.D. program and continued her work on finding the optimal structure for stronger, longer-lasting luminescence, with potential applications in bioimaging, anti-counterfeiting, and optical sensing. To date, she has presented her work in poster form at a Canadian Chemistry conference in June 2023 and has published two scientific papers as the first author and co-authored one paper.
