Chemical Modification of Analytes to Enhance Biochemical & Environmental Analysis

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For millennia humans have sought tools to fight infections and disease. The mid- to late 20th century saw the arrival of broad-spectrum antibiotics, cancer chemotherapy, antiviral drugs, cardiac medicines, and more thanks to the development of modern chemical and biochemical techniques and analytical instruments. Our understanding of our environment and pollution has undergone a similar revolution. The development of the next generation transformative medicines is now hampered by a shortage of understanding of the relevant biochemistry, rather than an inability to make molecules that treat the illness or disease. Thanks to its sensitivity and diversity of molecular information it provides, mass spectrometry is now the preeminent tool for molecular analysis in chemistry, biochemistry, and environmental analysis. Despite the exquisite nature of mass spectrometry, it is currently unable to address certain challenges and this application seeks to remedy this situation.In order to be observed by mass spectrometry, molecules must have one or more charges (+ or ). Unfortunately, some molecules will generate or host a charge much more easily than others. This means that two different molecules may be present in equal amounts but they will not produce equal signal strength in the mass spectrometry data. In turn, this makes it very difficult to accurately determine how much of a given molecule is present in a solution, especially if the solution is a mixture of many things, like a blood, tissue, or environmental sample. This is a critical issue in mass spectrometry because the fluctuation of the levels/concentrations of certain molecules are exactly the information required to better understand how diseases and illnesses work at a molecular level, as well as determine the concentration of different “compounds of concern” in the environment. This application seeks to address this by developing methods for the installation of fixed (i.e. non-moveable), permanent charges into organic/biological molecules. This highly original and innovative fundamental science research program, which stems from TrEnDi (Trimethylation Enhancement with Diazomethane, a technique developed by the applicant and a collaborator), is likely to lead to groundbreaking advances in our understanding of biochemistry and the environment. This will address Canada's socio-economic needs through applications in medicine, toxicology, forensics, polymers, food science and food safety, and environmental analysis of pollutants.