Sorption and reactivity in flexible amino acid-based nanoporous materials

沸石和碳是刚性吸附剂，它们构成了大型工业的基础。金属有机框架具有与这些经典体系互补的性质。提案团队已经展示了这些属性可以产生的新科学，特别是通过这些系统对客人的灵活响应。本提案利用了我们小组的两项最新进展（基于氨基酸的纳米多孔材料的分离，以及柔性开放框架材料可以作为通过衍射直接观察化学反应的容器的证明）来开发和理解功能化多孔材料的选择性吸附和反应性，并通过灵活性增强或允许。这两种新材料创造了相互关联的科学机遇。多孔氨基酸基材料具有比先前的手性开骨架材料更小的孔隙，但高密度的官能团排列在孔隙中，对于具有正确的相互作用位点的主体具有良好的对映选择性吸附- 1,3-二醇具有对映选择性吸附，而1,2-二醇表现出很小的分辨率。反应框架（发表在2007年的《科学》杂志上）由具有结构和反应作用的不同模块组成，并将两个参与孔内化学反应的客体分子预先放置在不同的位置，这表明这种系统的发展可以控制孔内的反应性和催化作用。该项目将通过扩展化学和开发结构、动力学和计算方法的综合组合来确定控制新系统行为的特征，从而开发这些材料，使其朝着具有类似酶性质的合成材料的长期目标发展。增强灵活性（被客人扭曲的主人）和允许灵活性（被刚性主人不接受的客人）的吸收将得到发展。实现这些目标所需要的三条链是——一个合成程序，生成更大的孔，增强控制分子定位的能力，并产生不同寻常的催化反应位点（例如氨基酸质子化以提供Bronsted酸位点）。这个方案涉及复杂的相场，在某些情况下必须是小规模的初始合成-搜寻反应，因此由材料发现中心的高通量设施得以实现；-一种计算方法，可以理解主人的灵活性如何控制对客人的反应，并允许识别利用新材料特性的客人。将开发一种筛选方法，以确定最适合对映选择性吸附的手性客体和可以定位多个客体并灵活响应它们的宿主。详细了解特定的吸附过程（以高ee吸附或独特的灵活性为特征）将涉及DFT和基于力场的MD（显示宿主动力学如何影响客体吸收），以确保确定电荷基（例如氢键）和色散相互作用的影响；-测量吸附，结构（衍射，专注于孔内反应性），动力学（NMR）和催化的实验程序，以测试计算预测并评估针对现有的对映选择性吸附，非手性分离和候选催化反应的行为；-一个工业研究实验室合作小组，对分离材料（ThermoFisher）进行具体评估，重点关注制药公司的特定目标（辉瑞），并协助开发建模方法（联合利华），重点关注宿主材料的灵活客体反应。

Zeolites and carbons are rigid sorbents which form the basis of large industries. Metal-organic frameworks have properties complementary to these classical systems. The proposal team have demonstrated the new science that can arise from these properties, in particular through the flexible response of these systems to guests. This proposal exploits two recent advances from our group (the isolation of nanoporous materials based on amino acids and the demonstration that flexible open-framework materials can act as containers for the direct observation of chemical reactions by diffraction) to develop and understand functionalised porous materials for selective sorption and reactivity enhanced or permitted by flexibility.The two new families of materials create linked scientific opportunities. The porous amino acid-based materials have smaller pores than previous chiral open-framework materials but the high density of functional groups lining the pores results in superior enantioselective sorption for guests which have the correct disposition of sites for interaction - 1,3-diols are enantioselectively sorbed whereas 1,2-diols show little resolution. The reactive frameworks (reported in Science 2007) consist of distinct modules with structural and reactive roles, and pre-position two guest molecules involved in an intrapore chemical reaction at distinct sites, suggesting the development of such systems for the control of reactivity and catalysis within the pores.The project will develop these materials towards the long-term target of synthetic materials with properties resembling those of enzymes, by expanding the chemistry and developing an integrated combination of structural, dynamics, and computational approaches to identify the features controlling the behaviour of the new systems. Flexibility-enhanced (host distortion by the guest) and flexibility-permitted (guest not admitted by the rigid host) sorption will be developed. The three strands required to achieve these goals are- a synthesis programme to generate larger pores with enhanced capability to control molecular positioning and generate unusual reactive sites for catalysis (e.g.amino acid protonation to afford Bronsted acid sites). This programme involves complex phase fields and in some cases necessarily small-scale initial synthesis-search reactions, and is thus enabled by the high-throughput facilities in the Centre for Materials Discovery;- a computational methodology which enables understanding of how host flexibility controls the response to guests, and permits the identification of guests which exploit the properties of the new materials. A screening methodology to permit the identification of chiral guests best suited to enantioselective sorption and of hosts which can locate multiple guests and respond flexibly to them will be developed. Detailed understanding of specific sorption processes (distinguished by high ee sorption or unique flexibility) will involve DFT and forcefield-based MD (showing how host dynamics influence guest uptake) to ensure the influence of both charge-based (e.g. hydrogen bonding) and dispersive interactions are identified;- an experimental programme measuring sorption, structure (diffraction, focussing on intra-pore reactivity), dynamics (NMR) and catalysis to both test computational prediction and evaluate the behaviour against an existing set of guests for enantioselective sorption, non-chiral separations and candidate catalytic reactions;- a partner group of industrial research labs to carry out specific evaluations of the materials for separations (ThermoFisher) focussed on specific targets of pharmaceutical interest (Pfizer) and assist development of the modelling approach (Unilever), focussing on flexible guest response by host materials.