Chemical Modification of Analytes to Enhance Biochemical & Environmental Analysis

几千年来，人类一直在寻找对抗感染和疾病的工具。世纪中后期，随着现代化学和生物化学技术以及分析仪器的发展，广谱抗生素、癌症化疗、抗病毒药物、心脏药物等相继问世。我们对环境和污染的理解也经历了类似的革命。** 下一代变革性药物的开发现在受到了对相关生物化学缺乏理解的阻碍，而不是无法制造治疗疾病的分子。由于其提供的分子信息的灵敏度和多样性，质谱法现在是化学，生物化学和环境分析中分子分析的杰出工具。尽管质谱法具有精致的性质，但它目前无法解决某些挑战，本申请寻求补救这种情况。为了被质谱法观察到，分子必须具有一个或多个电荷（+或）。不幸的是，有些分子比其他分子更容易产生或携带电荷。这意味着两种不同的分子可能以相等的量存在，但它们在质谱数据中不会产生相等的信号强度。反过来，这使得很难准确地确定溶液中存在多少给定分子，特别是如果溶液是许多东西的混合物，如血液，组织或环境样品。这是质谱分析中的一个关键问题，因为某些分子的水平/浓度的波动正是更好地了解疾病和疾病在分子水平上如何工作以及确定环境中不同“关注化合物”浓度所需的信息。本申请试图通过开发用于将固定（即不可移动）的永久电荷安装到有机/生物分子中的方法来解决这个问题。这项高度原创和创新的基础科学研究计划源于TrEnDi（重氮甲烷三甲基化增强，由申请人和合作者开发的技术），可能会导致我们对生物化学和环境的理解取得突破性进展。这将通过在医学、毒理学、法医学、聚合物、食品科学和食品安全以及污染物的环境分析方面的应用来满足加拿大的社会经济需求。

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.