GOALI: A Quantum Mechanics Based Method for Properties Predictions and Product Improvements Using Molecular Design

该奖项是根据2009年《美国复苏和再投资法案》(公法111-5)提供资金的。这项研究提案部分由特拉华大学化工系斯坦利·I·桑德勒教授的研究小组与特拉华州威尔明顿杜邦公司实验站的Steven Lustig博士和Michael Crawford博士合作研究的学术联络机会(GOALI)计划提供的资金支持。该项目将对能源和环境产生长期影响。热力学研究将集中于对特拉华大学最近开发的基于量子力学的物理化学性质预测方法COSMO-SAC的改进，以及它与杜邦大学Steven Lustig开发的分子设计方法的结合，用于科学和工业领域。本提案中有三个具体但相关的研究领域：改进COSMO-SAC基本模型，以更好地表示伦敦弥散相互作用，然后使用特拉华大学和杜邦公司现有的数据库对模型进行重新参数化；利用杜邦公司的拉曼光谱，对COSMO-SAC的基本假设和溶质分子构象在所在溶剂上的独立性的相关模型进行实验测试；以及将拟议的改进与COSMO设计方法相结合，开发一个自成一体的工具，可用于设计分子以实现某些性能目标。智力价值这一具有独创性和鲜明智力价值的建议有三个特点。第一种是将基于量子力学的方法以一种新颖的方式预测热力学性质与基于人工智能的方法相结合，以选择流体和混合物以满足产品或工艺的优化设计要求。第二是这种基于量子的方法的进一步发展，在基于更好的物理化学理论和描述的基础上，在处理色散和氢键能量的方法上有了显着的改进。最后，虽然已知溶液对分子构象的影响很重要，例如，在蛋白质的卷曲和解卷或聚合物和折叠和展开(变性)中，这种影响在描述小分子时被很大程度上忽略了。在这项研究中，PI将通过实验检验分子构象变化的重要性，然后将这些信息纳入热力学性质模型。更广泛的影响建议的研究最重要的影响是开发一种公众可用的全新设计工具，供化学家和工程师用于产品或溶剂的逆向工程，特别是那些具有环境可接受性的产品或溶剂。也就是说，一旦一种产品或溶剂的一组期望的性质已经确定，拟议的研究结果将允许识别具有这些性质的纯流体或混合物，即使没有实验数据或物质(S)甚至还没有合成。离子液体就是一个这样的例子，根据阴离子和阳离子的不同选择，有许多可能的离子液体，但只有几个已经被合成。另一个是选择一种新的制冷剂或制冷剂，以满足能源效率或环境标准。该方法的其他应用包括使用基于量子力学的理论来选择性地将物质结合到电子和生物底物上；估计毒性；以及设计具有所需药物配方和/或输送特性的药物和其他生物制品。除了这项研究的科学和工程影响外，至少一名博士和一名博士后助理将根据拟议的拨款接受培训，从而增加美国训练有素的专业人员队伍。此外，通过特拉华大学的RISE计划，我们将邀请来自未被充分代表的少数民族的本科生参与研究。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). The research proposal is supported in part through the funds from the Grant Opportunities for Academic Liaison with Industry (GOALI) program for cooperative research between the research group of Professor Stanley I. Sandler of the Department of Chemical Engineering at the University of Delaware and Drs. Steven Lustig and Michael Crawford at the Experimental Station of the DuPont Company in Wilmington Delaware. The project will have long term energy and environmental impact. It involves simulation/modeling and comparisons with experimentation.The thermodynamics research will focus on improvements to the recent quantum mechanics based physical and chemical properties prediction method, COSMO-SAC, developed at the University of Delaware, and its combination with a molecular design methodology developed by Steven Lustig at DuPont to areas of both scientific and industrial interest. There are three specific, but related areas of research in this proposal are improvement of the basic COSMO-SAC model to better represent London dispersion interactions, and then reparameterization of the model using databases available at the University of Delaware and at the DuPont Company; an experimental test of a fundamental assumption of the COSMO-SAC and related models of the independence of the solute molecular conformation on the solvent in which it is located using Raman spectroscopy at the DuPont Company; and combination of the proposed refinements with the COSMOdesign methodology to develop a self contained tool that can be used to design molecules to achieve certain performance goals. Intellectual Merit There are three features of this proposal of original and distinct intellectual merit. The first is the combination of a quantum mechanics based approach to predicting the thermodynamic properties in a novel manner with an artificial intelligence based method to choose fluids and mixtures to meet specifications for the optimal design of a product or process. Second is the further development of this quantum based method by a significant improvement in the way dispersion and hydrogen bonding energies are treated based on better physiochemical theory and descriptions. Finally, while the solution effects on conformations of molecules is known to be important, for example, in the coiling and uncoiling or polymers and folding and unfolding (denaturation) of proteins, this effect is largely ignored in the description of smaller molecules. The PIs will examine the importance of changes in molecular conformation experimentally in this research, and then incorporate this information into thermodynamic properties model. Broader Impacts The most important impact of the research proposed is the development of a publically-available, completely new design tool for chemists and engineers to use in reverse engineering of a product or solvent, and especially those with environmentally acceptability. That is, once a desired set of properties for a product or solvent have been specified, the result of the proposed research will allow pure fluids or mixtures to be identified that have these properties, even if there are no experimental data or the substance(s)has not yet even been synthesized. One such example is ionic liquids, of which there are many possible based on different choices of anion and cation, while only a few have been synthesized. Another would be in choosing a new refrigerant or refrigerant to meet energy efficient or environmental standards. Still other applications of the method include using the quantum mechanical based theory to selective binding of substances to electronic and biological substrates; estimating toxicity; and to the design of pharmaceutical and other biologics with desired drug formulation and/or delivery properties. In addition to the scientific and engineering impact of the research, at least one Ph.D. and one postdoctoral associate will receive training under the proposed grant, thereby increasing the U.S. pool of trained professionals. Also, through the RISE program of the University of Delaware, we will involve undergraduate students from underrepresented minorities in the research.