International Collaboration in Chemistry: Aqueous Host-Guest Chemistry with Self-Assembling Metal-templated Cages

随着国际化学合作（ICC）奖，明尼苏达大学的Laura Gagliardi教授（PI）和Christopher J. Cramer教授（共同PI），由大分子，超分子和纳米化学（MSN）计划和化学理论，模型和计算方法计划（CTMCM）在化学系以及NSF国际科学与工程办公室（OISE）共同支持，将与英国剑桥大学化学系的Jonathan Nitschke教授进行研究，以评估影响自组装金属模板笼中小至中等大小的有机分子在水溶液主客体化学中结合和识别的基本因素。通过利用建模和实验之间的螺旋反馈，他们将确定复合物中的关键空间和静电相互作用，控制这些相互作用将有助于改进主客体组合的合理设计。将采用基于量子力学和分子力学的理论模型。量子力学模型将被用来补充实验与基准数据的经典机械力场的选择，也被用来计算光谱数据（例如，NMR和UV/维斯）以与实验主体-客体组合进行比较。经典的机械力场模型将被用来模拟主客体组合的动力学行为，并预测与水结合事件相关的平均力的潜力。有了足够的验证数据在手，在电脑设计的努力，将集中在主-客体组合显示增强的选择性和bindingefficiency.Molecular笼合成努力的目标已被证明稳定不稳定的分子，如白色磷，自发易燃和剧毒形式的元素。笼也可以选择性地加速（催化）反应结合到高能量的反应中间体，从而降低它们的能量。为了扩展这些用途并开发新的用途，必须对封装分子与其宿主之间的弱相互作用有基本的了解。这个合作研究项目将使一个美国-英国团队联合收割机理论和实验相结合，以了解这种"主客体化学"的基本原理，目标是能够为尚未梦想的应用设计新的笼子。

With an International Collaborations in Chemistry (ICC) award, Professors Laura Gagliardi (PI) and Christopher J. Cramer (co-PI) of the University of Minnesota, supported jointly by the Macromolecular, Supramolecular, and Nanochemistry (MSN) Program and the Chemical Theory, Models and Computational Methods Program (CTMCM) in the Division of Chemistry as well as the NSF Office of International Science and Engineering (OISE), will engage in research with Professor Jonathan Nitschke of the Department of Chemistry, Cambridge University, United Kingdom, to assess the fundamental factors affecting binding and recognition in the aqueous host-guest chemistry of small to moderate-sized organic molecules inside self-assembling, metal-templated cages. By taking advantage of spiral feedback between modeling and experiment, they will identify key steric and electrostatic interactions in the complexes, the control of which will facilitate the rational design of improved host-guest combinations. Theoretical models based on both quantum and molecular mechanics will be employed. Quantum mechanical models will be employed to supplement experiment with benchmark data for the selection of classical mechanical force fields and also be used to compute spectral data (e.g., NMR and UV/Vis) in order to compare to experimental host-guest combinations. Classical mechanical force field modeling will be used to simulate the dynamical behavior of host-guest combinations and for the prediction of potentials of mean force associated with aqueous binding events. With sufficient validating data in hand, in silico design efforts will be undertaken with the goal of focusing synthetic efforts on host-guest combinations showing enhanced selectivity and binding efficiencies.Molecular cages have been shown to stabilize unstable molecules, such as white phosphorus, a spontaneously-flammable and highly toxic form of the element. Cages can also selectively speed up (catalyze) reactions by binding to high-energy reactive intermediates, thus lowering their energies. In order to extend these uses and develop new ones, fundamental understanding must be gained as to the weak interactions between encapsulated molecules and their hosts. This collaborative research project will allow a US-UK team to combine theory and experiment to come to an understanding of the fundamentals of this 'host-guest chemistry' with the goal of being able to design new cages for applications as yet undreamt-of.