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DMREF: Accelerated discovery of metastable but persistent contact insecticide crystal polymorphs for enhanced activity and sustainability

DMREF：加速发现亚稳态但持久的接触性杀虫剂晶体多晶型物，以增强活性和可持续性

基本信息

批准号：
2118890
负责人：
Mark Tuckerman
金额：
$ 171.36万
依托单位：
New York University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2118890&HistoricalAwards=false
关键词：
DMREF Accelerated discovery metastable but

项目摘要

Non-technical Description: The World Health Organization estimates that malaria and other vector-borne infectious diseases, such as Zika or dengue fever, are responsible for more than 700,000 deaths worldwide annually. An essential component in the fight against malaria is the control of disease vectors through the use of contact insecticides for indoor residual spraying and insecticide-treated nets. Contact insecticides are powders of organic crystalline materials. As mosquitoes rest on the powder particles, they absorb the active substance through their tarsi (feet) to lethal effect. New York University investigators previously demonstrated that the efficacy of contact insecticides strongly depends on the identity of their crystalline forms, otherwise known as polymorphs, which have identical molecular compositions but different crystal structures. The more active polymorphs must also exhibit a high stability against transformation to less active polymorphs for the duration of their application. The central objective of this project is a knowledge-guided design, through computation and experiment, of metastable crystalline forms with superior properties for their target application. In the context of contact insecticides, this will allow less toxicant to be used, reduce environmental impact, and, thereby, meet key sustainability goals on multiple fronts. Various workshops, including Computer Crystals for Kids, Machine Learning for Kids, and Crystal Kaleidoscope, will convey the science of the project to K-12 students. Special attention will be provided to engage Black, Latino, and Native American students through the Collegiate Science Technology Entry Program.Technical Description: The application of metastable polymorphs of molecular crystals in the management of vector-borne diseases such as malaria and dengue fever through innovations in contact insecticide formulations represents a new and sustainable target of opportunity. Accelerated discovery of such metastable polymorphs with low thermodynamic yet high kinetic stability constitutes a key challenge that can only be met using a tightly integrated computational and experimental workflow. Starting with twelve known contact insecticides approved by the World Health Organization for indoor residual spraying (including pyrethroids, organophosphates, carbamates, and neonicotinoids), the project will explore innovative approaches to crystal polymorphs that meet the aforementioned criteria, which are essential to insecticide efficacy that relies on physical contact between insect tarsi and crystal surfaces in indoor residual spraying applications and insecticide-treated nets. Experimentally, these metastable polymorphs can be obtained from melt or solution, by (cross-)nucleation, phase transformations, or growth under nanoconfinement. The experimental work will be complemented by the development of a theoretical framework focused on the formation of energetically accessible polymorphs – driven by both thermodynamic and kinetic factors – as well as the transformation between different polymorphs and their surface properties. These tasks are beyond the reach of standard computational tools, requiring the development of new theoretical methodologies that combine the strength of enhanced molecular simulations and machine learning. Initial computational results will be validated by experimental data to improve the theoretical framework. Similarly, theoretical predictions will be used to guide and refine experimental protocols. This iterative loop of mutual feedback will eventually converge toward comprehensive and reliable workflows that will accelerate the discovery and development of metastable polymorphs with exceptional properties, in accord with the goals of the Materials Genome Initiative. Various workshops, including Computer Crystals for Kids, Machine Learning for Kids, and Crystal Kaleidoscope, will convey the science of the project to K-12 students. Special attention will be provided to engage Black, Latino, and Native American students through the Collegiate Science Technology Entry Program.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

非技术描述：据世界卫生组织估计，疟疾和其他病媒传染病，如寨卡病毒或登革热，每年造成全球70多万人死亡。防治疟疾的一个重要组成部分是通过使用接触杀虫剂进行室内滞留喷洒和使用驱虫蚊帐来控制病媒。接触杀虫剂是有机晶体材料的粉末。当蚊子停在粉末颗粒上时，它们通过它们的跗骨（脚）吸收活性物质，达到致命的效果。纽约大学的研究人员先前证明，接触杀虫剂的功效在很大程度上取决于其结晶形式的特性，也称为多晶型物，其具有相同的分子组成但不同的晶体结构。活性更高的多晶型物还必须在其应用期间表现出高的稳定性，以防止转化为活性更低的多晶型物。该项目的中心目标是通过计算和实验，以知识为指导设计具有上级性能的亚稳晶体形式，以满足其目标应用。在接触杀虫剂的背景下，这将允许使用更少的有毒物质，减少对环境的影响，从而在多个方面实现关键的可持续性目标。各种研讨会，包括儿童计算机晶体，儿童机器学习和水晶万花筒，将向K-12学生传达该项目的科学。特别注意将提供参与黑人，拉丁美洲和美洲原住民的学生通过大学科学技术入门Program.Technical描述：亚稳多晶型分子晶体的应用在管理的媒介传播的疾病，如疟疾和登革热通过接触杀虫剂配方的创新代表了一个新的和可持续的机会目标。加速发现这种具有低热力学但高动力学稳定性的亚稳多晶型物构成了一个关键挑战，只能使用紧密集成的计算和实验工作流程来满足。从世界卫生组织批准用于室内滞留喷洒的12种已知接触杀虫剂开始（包括拟除虫菊酯、有机磷酸酯、氨基甲酸酯和烟碱类），该项目将探索符合上述标准的晶体多晶型物的创新方法，其对于依赖于在室内滞留喷洒应用中昆虫跗骨和晶体表面之间的物理接触的杀虫剂功效是必不可少的，治疗网在实验上，这些亚稳多晶型物可以从熔体或溶液中通过（交叉）成核、相变或在纳米约束下生长获得。实验工作将得到补充的理论框架的发展，重点是形成能量可访问的多晶型物-由热力学和动力学因素驱动-以及不同的多晶型物和它们的表面性质之间的转换。这些任务超出了标准计算工具的范围，需要开发新的理论方法，联合收割机增强的分子模拟和机器学习的优势。初步计算结果将通过实验数据进行验证，以完善理论框架。同样，理论预测将用于指导和完善实验方案。这种相互反馈的迭代循环最终将朝着全面和可靠的工作流程收敛，这将加速具有特殊性质的亚稳态多晶型物的发现和开发，雅阁材料基因组计划的目标。各种研讨会，包括儿童计算机晶体，儿童机器学习和水晶万花筒，将向K-12学生传达该项目的科学。通过大学科学技术入学计划，将特别关注黑人，拉丁美洲人和美洲原住民学生的参与。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。