Theoretical Studies of Biochemical and Environmental Relevance

生化和环境相关性的理论研究

• 批准号: RGPIN-2022-05432
• 负责人: MoraDiez, Nelaine
• 金额: $ 2.62万
• 依托单位: Thompson Rivers University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762194
• 关键词: Theoretical; Studies; Biochemical; Environmental; Relevance

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.

强大计算机的可用性以及新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，涉及化学系统的研究，由于成本、时间、资源和系统复杂性，这些化学系统的实验数据不足。第一个研究领域旨在寻找与阿片类药物成瘾相关的国际健康危机的解决方案。通过开发一种理论方法来建立对阿片类药物酸解离常数的高预测能力，我们将探索简单的化学修饰对产生对发炎组织中阿片类受体具有更大亲和力的阿片类药物的影响，由于酸中毒，阿片类药物受体的亲和力较低。 pH 值高于健康细胞的 pH 值。当阿片类药物仅针对发炎组织时，其成瘾潜力会显着降低（或可能消除）。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）是否比阿片类药物更有效地与大脑中的阿片类受体相互作用，以了解它们最近建议用于治疗阿片类药物添加的用途。第二个研究方向涉及与加拿大核工业高度相关的计算。加拿大氘铀 (CANDU) 核反应堆使用重水作为中子慢化剂和主冷却剂。我们将开发模型来了解主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。我们提出的工作将增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。