Unified Approach to Molecular Recognition and Catalysis

分子识别和催化的统一方法*当谈到为人体开发高效和选择性催化剂时，大自然最了解。从酶如何催化反应并将其应用于开发对世界有用的化学催化剂中，可以学到很多东西。采用这种仿生方法可以导致治疗疾病的药物的开发，或者清洁环境和清洁能源催化剂的开发。我们将采取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。在第一部分中，通过计算设计并合成了磷酸吡哆醛(维生素B6)模型。我们的目的是更好地了解自然界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。对吡哆醛作用机制的更好理解导致了抗菌药物和抗帕金森药物的发展。我们还计划利用我们的吡哆醛模型开发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，我们计划更好地理解它，同时尝试做自然做不到的事情。*在提案的第二部分，我们计划使用计算来更好地理解立体选择性的起源和众所周知的催化剂的反应性。在过去的三四十年里，已经开发出了用于制造药物的高效和有用的催化剂。然而，在开发立体选择性催化剂方面，机缘巧合仍然发挥着重要作用。我们计划研究Jacobsen的环氧化和开环催化剂的立体选择性的来源。更好地理解空间选择性的来源可能会导致更合理的优质催化剂的设计。我们还计划使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活性的来源。这些知识将被用于开发快速有效地将二氧化碳转化为有用材料的催化剂。虽然二氧化碳经常被指责为污染全球的最不受欢迎的工业产品，但它也可以成为清洁能源的原料。*1.吡哆醇类化合物。*a)基础知识。*b)包括氨基醇和氨基酸在内的手性单胺的制造方法。*2.催化剂的立体选择性和反应性*a)环氧化的立体选择性*b)水解环的立体选择性--环氧化物的开环*c)人工金属水解酶的反应活性*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******