Templated Molecular Recognition Materials: Theory and Simulation

保罗·R·范·塔塞尔韦恩州立大学《模板化分子识别材料：理论与模拟》分子识别(MR)是一个用来描述弱相互作用位点互补模式之间强而高度特异的结合的术语。在生命系统中，MR是许多生物学功能的起源，包括信号转导和组装指导。具有MR功能的全合成材料在生物模拟物、传感器、组织工程底物和分离/纯化试剂等方面具有潜在的应用价值，与包含真正生物结构(蛋白质、多肽、核酸)的传统材料相比，在成本和稳定性方面具有明显的优势。制备合成磁共振材料的一个通用策略是在分子或超分子模板存在的情况下，通过功能化的、可聚合的单体进行纳米级组装。经过聚合和模板去除后，材料将(理想情况下)具有纳米级的形状和图案，与模板的形状和图案相辅相成。模板分子识别(TMR)背后的想法很简单，一些应用已经出现(最著名的是分子印迹聚合物)。然而，由于目前对模板形态对材料结构和识别能力的影响等元素问题的定量了解较差，限制了进展。特别是，目前还没有理论描述来根据模板和单体结构以及合成变量(例如前体组成、温度等)来预测识别。开发这样的描述是这项工作的总体目标。受TMR形成过程的启发，提出了一个基于分子的模型，其起点是相对于分子力场处于平衡状态的功能单体/模板/溶剂混合物。单体的聚合是通过分子位置的瞬间熄灭或冻结来解释的。然后除去模板和溶剂，剩下的(淬火的)单体作为初始模型材料，将含有与原始模板相同或结构相关的分子的新溶液浸入其中。聚合后的结构变化也可以通过膨胀/收缩或去致密来实现。特别重要的是我们提出的基于平衡的理论方法，利用最初为研究自旋玻璃而开发的复制方法来确定模型体系的结合热力学。我们还提出了互补的分子计算机模拟。第一个目标是为具有TMR能力的简单模型系统建立这种理论描述。用积分方程组理论计算了该模型材料中链状分子和团簇吸附的热力学。这一意义将是TMR的第一个理论描述。第二个目标是将理论描述应用于精心选择的模型单体、模板和吸附结构，以回答关于TMR的重要基本问题。这一意义将是对TMR的第一个基本的、分子水平的理解。第三个目标是使用理论描述来预测文献中报告的系统中的TMR。其意义将是第一个预测TMR的模型。产业和社会影响：所提出的TMR的理论描述将是开发能够高亲和力结合的纳米结构材料的有价值的工具。能够进行合理设计的材料包括分子印迹聚合物(MIP)、定向表面组装的单分子膜、模板功能化无机物和蛋白质模板化生物仿生材料--这些材料可能会作为传感器、选择性吸附剂和组织工程基质而得到重要应用，并在成本、稳定性和生物相容性方面比传统材料具有显著的优势，这些材料中包含了真正的生物结构(蛋白质、多肽、核酸)。使用该描述，可以克服当前的实际问题，例如识别位点的密度低、可访问性差、以及不同的结合强度。此外，这些有机形成的材料在水环境中发挥作用的能力将得到增强。人们可以想象，在未来，通过模板进行的纳米结构修改通常被用来为特定的粘合应用量身定做材料。此外，这所大型城市大学将鼓励少数族裔和妇女参与其中。最后，计划举行一系列研讨会，要求学生就他们的研究内容做报告。

Paul R. Van TasselWayne State University "Templated Molecular Recognition Materials: Theory and Simulation"Molecular recognition (MR) is a term used to describe the strong and highly specific bindingbetween complementary patterns of weakly interacting sites. In living systems, MR is at the origin of many biological functions, including signal transduction and assembly guidance. Fully synthetic materials capable of MR are potentially useful as bio-mimics, sensors, tissue engineering substrates, and separation/purification agents and offer clear advantages in terms of cost and robustness compared to conventional materials into which true biological structures (proteins, peptides, nucleic acids) are incorporated. A universal strategy for preparing synthetic MR materials is through the nanoscale assembly of functionalized, polymerizable monomers in the presence of molecular or supramolecular templates. Following polymerization and template removal, the material will (ideally) possess a shape and pattern, on a nanometer length scale, that complements those of the template.The idea behind templated molecular recognition (TMR) is straightforward and some applications have appeared (most notably, the molecularly imprinted polymers). However, progress is limited by the current poor quantitative understanding of elemental issues like the influence of template morphology on the material's structure and recognition ability. In particular, no theoretical description is currently available to predict recognition from template and monomer structures and synthesis variables (e.g. precursor composition, temperature, etc.). It is the overall goal of this work to develop such a description. A molecular-based model inspired by the TMR formation process is proposed whose starting point is a functional monomer / template / solvent mixture in equilibrium with respect to a molecular force field. Polymerization of the monomers is accounted for by an instantaneous quench, or freezing, of the molecular positions. The template and solvent are then removed, and the remaining (quenched) monomers serve as the initial model material into which is immersed a new solution containing molecules identical or structurally related to the original template. Post-polymerization structural alterations are also possible through expansion/contraction or de-densification. Of particular significance is our proposed equilibrium based theoretical approach, exploiting the replica method originally developed to study spinglasses, to determine the binding thermodynamics of the model system. Complementary molecular computer simulations are also proposed.The first objective is to establish this theoretical description for simple model systems capable ofTMR. An integral equation theory will be developed to calculate the thermodynamics of chain molecule and cluster adsorption in this model material. The significance will be the first theoretical description of TMR. The second objective is to apply the theoretical description to carefully chosen model monomer, template, and adsorbate structures in order to answer to important fundamental questions on TMR. The significance will be the first fundamental, molecular-level understanding of TMR. The third objective is to use the theoretical description to predict TMR in a system reported in the literature. The significance will be the first predictive model of TMR.Industrial and Societal Impact:The proposed theoretical description of TMR will be a valuable tool in the development ofnanostructured materials capable of high affinity binding. Examples of materials whose rational design will be enabled include molecularly imprinted polymers (MIPs), directed surface assembled monolayers, template functionalized inorganics, and protein templated biomimics - these may find important application as sensors, selective adsorbents, and tissue engineering substrates and offer significant advantages in cost, robustness, and biocompatibility over conventional materials into which true biological structures (proteins, peptides, nucleic acids) are incorporated. Using this description, current practical problems such as low density, poor accessibility, and heterogeneous binding strength of the recognition sites may be overcome. Additionally, the ability of these organically formed materials to function in an aqueous environment will be enhanced. One can envision a future where nanostructural modification by templating is routinely used to tailor materials for specific binding applications.Also, minorities and women will be encouraged to participate at this large, urban university. Finally, a seminar series is planned in which the students will be required to make presentations relating to their part of the research.