Sorption and reactivity in flexible amino acid-based nanoporous materials

沸石和碳是刚性吸附剂，构成了大型工业的基础。金属有机框架具有与这些经典系统互补的性质。提案团队已经展示了这些特性可能产生的新科学，特别是通过这些系统对客人的灵活响应。该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和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，以实现选择性吸附和反应性增强或允许的灵活性。这两个新的材料家族创造了相关的科学机会。基于氨基酸的多孔材料具有比以前的手性开放骨架材料更小的孔，但是内衬孔的高密度官能团导致对具有正确的相互作用位点布置的客体的上级对映选择性吸附-1，3-二醇对映选择性吸附，而1，2-二醇显示出很小的分辨率。Reactive框架（发表于Science 2007）由具有结构和反应作用的不同模块组成，并将参与孔内化学反应的两个客体分子预先定位在不同位点，这表明开发此类系统用于控制孔内的反应性和催化作用。该项目将朝着具有类似酶的性质的合成材料的长期目标开发这些材料，通过扩大化学和发展结构，动力学和计算方法的综合组合，以确定控制新系统行为的特征。将开发可吸附性增强（客体对主体的扭曲）和灵活性允许（刚性主体不允许客体进入）吸附。实现这些目标所需的三条链是-合成程序，以产生更大的孔，具有增强的控制分子定位的能力，并产生不寻常的催化反应位点（例如，氨基酸质子化以提供布朗斯台德酸位点）。该计划涉及复杂的相场，在某些情况下，必然是小规模的初始合成搜索反应，因此能够通过材料发现中心的高通量设施实现;-一种计算方法，能够理解主机灵活性如何控制对客人的响应，并允许识别利用新材料特性的客人。将开发一种筛选方法，以确定最适合对映体选择性吸附的手性客体和能够定位多个客体并对其作出灵活反应的主体。详细了解特定的吸附过程（通过高ee吸附或独特的灵活性区分）将涉及DFT和基于力场的MD（显示主体动力学如何影响客体吸收）以确保基于电荷的（如氢键）和分散的相互作用被确定;- 测量吸附、结构的实验计划（衍射，聚焦于孔内反应性），动力学（NMR）和催化来测试计算预测和评估针对现有的一组客体的对映选择性吸附的行为，非手性分离和候选催化反应;-一个工业研究实验室的合作伙伴小组，对分离材料（ThermoFisher）进行具体评估，重点关注特定的药物目标（辉瑞），并协助开发建模方法（联合利华），重点关注主体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.