Unified Approach to Molecular Recognition and Catalysis

分子识别和催化的统一方法****当涉及到为身体开发高效和选择性催化剂时，大自然知道得最多。从酶如何催化反应中可以学到很多东西，并将其应用于开发对世界有用的化学催化剂。采用这种仿生方法可以开发用于治疗疾病的药物或开发用于清洁环境和清洁能源的催化剂。我们将采用计算和实验两种方法来解决我们的研究问题。****我的建议主要有两个部分。第一部分通过计算和合成设计磷酸吡哆醛（维生素B6）模型。我们的目标是更好地了解大自然如何使用磷酸吡哆醛作为辅酶来催化各种基本反应，如氨基酸的合成和分解。更好地了解吡哆醛的作用机制已经导致抗菌和抗帕金森药物的发展。我们还计划开发利用我们的吡哆醛模型制造非天然氨基酸和其他生物活性胺的方法。通过模仿自然，我们打算更好地理解它，同时尝试做自然不能做的事情。****在提案的第二部分，我们计划使用计算来更好地了解已知催化剂的立体选择性和反应性的起源。在过去的30或40年里，高效和有用的催化剂已经被开发出来用于制造药物。然而，在开发立体选择性催化剂时，意外发现仍然起着重要作用。我们计划研究Jacobsen环氧化和开环催化剂立体选择性的来源。更好地了解立体选择性的起源可以导致更合理的设计优良的催化剂。我们还计划利用计算来更好地了解我们过去开发的人工水解金属酶的反应性起源。这些知识将应用于开发催化剂，快速有效地将二氧化碳转化为有用的材料。虽然二氧化碳经常被指责为污染地球的最不受欢迎的工业产物，但它也可以成为清洁能源的原材料。****1。吡哆醛模拟。****a)基础知识。****b)手性单胺的制备方法，包括氨基醇和氨基酸。****催化剂的立体选择性和反应性的来源****a)环氧化的立体选择性****b)环氧化物水解开环的立体选择性****c)人工水解金属酶的反应性****d) CO2活化******

Unified Approach to Molecular Recognition and Catalysis****Nature knows best when it comes to developing highly efficient and selective catalysts for the body. Much can be learned from how enzymes catalyze reactions and apply them to developing chemical catalysts that are useful for the world. Taking this biomimetic approach can lead to development of pharmaceutical drugs for curing illnesses or to development of catalysts for clean environment and clean energy. Both computational and experimental approaches will be taken to solve our research problems.****There are two main parts to my proposal. In the first part, pyridoxal phosphate (vitamin B6) models will be designed by computation and synthesized. Our aim is to better understand how nature uses pyridoxal phosphate as coenzyme to catalyze a wide variety of fundamental reactions like amino acid synthesis and breakdown. Better understanding of the mechanism of action of pyridoxal has led to the development of antibacterial as well as antiparkinsons drugs. We also plan to develop methods for making unnatural amino acids and other biologically active amines using our pyridoxal models. By mimicking nature, we plan to better understand it and at the same time try to do what nature cannot do.****In the second part of the proposal, we plan to use computation to better understand the origin of stereoselectivity and reactivity of well-known catalysts. Highly efficient and useful catalysts have been developed in the past 30 or 40 years for making drugs. Yet when it comes to developing stereoselective catalysts, serendipity still plays an important role. We plan to investigate the origin of stereoselectivity of Jacobsen's epoxidation and ring-opening catalysts. Better understanding of the origin of stereselectivity could lead to more rational designs of superior catalysts. We also plan to use computation to better understand the origin of reactivity of artificial hydrolytic metalloenzymes that we developed in the past. This knowledge will be applied to developing catalysts that rapidly and efficiently convert CO2 to useful materials. While carbon dioxide is often blamed as the most undesirable product of industry that pollutes the globe, it can also be raw material for clean energy.****1. Pyridoxal mimics.****a) Fundamental knowledge.****b) Methods for making chiral monoamines including amino alcohols and amino acids.****2. Origin of stereoselectivity and reactivity of catalysts****a) Stereoselectivity of epoxidation****b) Stereoselectivity of hydrolytic ring-opening of epoxides****c) Reactivity of artificial hydrolytic metalloenzymes****d) CO2 activation******