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：世界卫生组织估计疟疾和其他媒介传染性疾病发烧，每年在全球范围内有700,000多人死亡。由于蚊子在粉末粒子上，造成杀虫剂晶体材料。 HA相同的分子组成但UST在Theis Project的持续时间内表现出高度的稳定性，可转化为活性的多晶型物。他们的目标应用程序可以减少毒性，从而减少环境影响，从而使孩子们的机器学习和水晶万花筒将项目的科学传达给K-12学生。黑人和美洲原住民的学生通过大学技术专业人员。技术描述：分子晶体在媒介传播的laria和登革热的管理中的应用，通过Contacticide Formulations中的创新，一种新的和可持续的机会目标。稳定征兵只能使用世界卫生组织批准的十二个已知的接触杀虫剂才能通过室内残留喷涂和新烟碱素来应对的关键挑战，该项目将创新的方法tolystal polystal polymorphs，这些多态多晶型物具有上述标准对杀虫剂的效率，昆虫tarsi和晶体表面之间的物理接触在室内残留的spplicatietide网络中，可以通过融化或溶液来获得（跨 - ）成核，纳米芬的生长。框架上的框架是能量可访问的多晶型物和动力学因素 - 随着不同的多晶型物及其表面特性之间的转化结果数据以改进理论框架和完善的实验协议。倡议。 Demed认为值得通过Toundation的智力优点和更广泛影响的评论标准来评估值得支持。