Theoretical Studies of Biochemical and Environmental Relevance

强大的计算机的可用性以及新的理论方法和算法的发展促进了理论研究，这两者都使计算化学成为实验化学研究的补充工具。理论化学的拟议研究涵盖两个领域，涉及由于成本，时间，资源和系统复杂性而无法获得足够实验数据的化学系统的研究。第一个研究领域旨在为与阿片类药物成瘾有关的国际健康危机找到解决方案。通过开发一种理论方法来建立阿片类药物的酸解离常数的高预测能力，我们将探索简单的化学修饰在创建阿片类药物中的作用，这些阿片类药物对炎症组织中的阿片受体具有更大的亲和力，由于酸中毒，pH值低于健康细胞。阿片类药物的成瘾潜力显着降低（或可能消除）时，他们只针对发炎组织。该研究领域的另一个分支旨在确定大麻素（大麻中发现的相关物质）是否比阿片类药物与大脑中的阿片类受体更有效地相互作用，以了解其最近建议用于治疗阿片类药物添加。第二个研究流涉及与加拿大核工业高度相关的计算。加拿大的重水铀（CANDU）核反应堆使用重水作为中子减速剂和主冷却剂。我们将开发模型，以了解在一次冷却剂回路中存在的水热条件（非常高的温度和压力）下弱酸和过渡金属络合物的化学性质。我们提出的工作将推进我们对重水如何影响化学系统热力学的理解，同时提供有价值的数据，有助于CANDU核反应堆的技术改进。

Theoretical research is facilitated by the availability of powerful computers and the development of new theoretical methods and algorithms, both of which have made computational chemistry a complementary tool to experimental chemical research. The proposed research in theoretical chemistry covers two areas and deals with the study of chemical systems for which insufficient experimental data are available due to cost, time, resources, and system complexities. The first research area aims to find solutions for the international health crisis related to opioid addiction. By developing a theoretical methodology to establish a high predictive power for the acid dissociation constants of opioids, we will explore the effect of simple chemical modifications in creating opioids with greater affinity for opioid receptors in inflamed tissue, that due to acidosis, is at a lower pH than that of healthy cells. The addictive potential of opioids is significantly reduced (or perhaps eliminated) when they only target inflamed tissue. Another branch of this area of study aims to determine if cannabinoids (relevant substances found in cannabis) interact more effectively than opioids with opioid receptors in the brain to understand their recently suggested use to treat opioid addition. The second research stream involves calculations that are highly relevant for the Canadian nuclear industry. CANadian Deuterium Uranium (CANDU) nuclear reactors use heavy water as a neutron moderator and primary coolant. We will develop models to understand the chemistry of weak acids and transition metal complexes under hydrothermal conditions (very high temperatures and pressures) present in the primary coolant circuits. Our proposed work will advance our understanding of how heavy water affects the thermodynamics of chemical systems, while providing valuable data that will contribute to the technological improvement of CANDU nuclear reactors.