Templated Molecular Recognition Materials: Theory and Simulation

Paul R. Van TasselWayne州立大学“模板分子识别材料：理论与模拟”分子识别（MR）是一个术语，用于描述弱相互作用位点互补模式之间的强和高度特异性结合。在生命系统中，MR是许多生物功能的起源，包括信号转导和装配指导。具有MR功能的全合成材料在仿生学、传感器、组织工程底物和分离/纯化剂等方面具有潜在的用途，与包含真正生物结构（蛋白质、多肽、核酸）的传统材料相比，在成本和稳健性方面具有明显的优势。制备合成MR材料的通用策略是通过在分子或超分子模板存在下的功能化、可聚合单体的纳米级组装。在聚合和模板去除之后，材料将（理想地）在纳米长度尺度上具有形状和图案，以补充模板的形状和图案。模板分子识别（TMR）背后的想法很简单，并且已经出现了一些应用（最值得注意的是，分子印迹聚合物）。然而，目前对模板形态对材料结构和识别能力的影响等基本问题的定量理解不足，限制了研究的进展。特别是，目前尚无理论描述来预测模板和单体结构以及合成变量（例如前驱体组成，温度等）的识别。开发这样的描述是本工作的总体目标。在TMR形成过程的启发下，提出了一个基于分子的模型，其起点是相对于分子力场平衡的功能单体/模板/溶剂混合物。单体的聚合是由分子位置的瞬时猝灭或冻结引起的。然后移除模板和溶剂，剩余的（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。聚合后的结构改变也可能通过膨胀/收缩或脱密。特别重要的是，我们提出了基于平衡的理论方法，利用最初用于研究旋流镜的复制方法，来确定模型系统的结合热力学。互补的分子计算机模拟也被提出。第一个目标是为能够进行tmr的简单模型系统建立这种理论描述。将建立一个积分方程理论来计算该模型材料中链式分子和团簇吸附的热力学。其意义将是首次对TMR进行理论描述。第二个目标是将理论描述应用于精心选择的模型单体、模板和吸附质结构，以回答关于TMR的重要基本问题。其意义将是对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道的系统中的TMR。该意义将是TMR的第一个预测模型。工业和社会影响：提出的TMR理论描述将是开发具有高亲和力结合的纳米结构材料的宝贵工具。能够实现合理设计的材料包括分子印迹聚合物（MIPs）、定向表面组装单层、模板功能化无机物和蛋白质模板仿生物——这些材料可能会在传感器、选择性吸附剂和组织工程基质方面得到重要应用，并且在成本、稳健性和生物相容性方面比传统材料具有显著优势，其中真正的生物结构(蛋白质、肽、核酸)被合并。利用这一描述，可以克服当前的实际问题，如低密度、低可及性和非均匀结合强度的识别位点。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。我们可以设想，未来通过模板的纳米结构修饰通常用于定制特定粘合应用的材料。此外，少数民族和妇女将被鼓励参加这所大型城市大学。最后，计划举办一系列研讨会，要求学生就他们的研究部分做报告。

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.