Templated Molecular Recognition Materials: Theory and Simulation

Paul R.货车TasselWayne州立大学“模板分子识别材料：理论与模拟“分子识别（MR）是一个用来描述弱相互作用位点互补模式之间强而高度特异性结合的术语。在生命系统中，MR是许多生物功能的起源，包括信号转导和组装指导。能够进行MR的全合成材料潜在地可用作生物模拟物、传感器、组织工程基底和分离/纯化剂，并且与其中掺入真实生物结构（蛋白质、肽、核酸）的常规材料相比，在成本和稳健性方面提供明显的优势。用于制备合成MR材料的通用策略是通过在分子或超分子模板的存在下官能化的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）具有纳米长度尺度上的形状和图案，与模板的形状和图案互补。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，进展是有限的，如模板形态对材料的结构和识别能力的影响等基本问题，目前的定量理解差。特别是，目前没有理论描述可用于预测从模板和单体结构和合成变量（例如，前体组成，温度等）的识别。这是这项工作的总体目标，发展这样一个描述。一个基于分子的模型的启发TMR形成过程中，提出了其出发点是一个功能单体/模板/溶剂混合物在平衡相对于分子力场。单体的聚合是由分子位置的瞬时淬灭或冻结来解释的。然后除去模板和溶剂，剩余的（淬灭的）单体用作初始模型材料，其中浸入含有与原始模板相同或结构上相关的分子的新溶液。通过膨胀/收缩或去致密化，聚合后结构改变也是可能的。特别重要的是，我们提出的平衡为基础的理论方法，利用复制品的方法最初开发的研究spinglasses，以确定模型系统的结合热力学。补充分子计算机模拟也被提出。第一个目标是建立这种理论描述的简单模型系统能够TMR。应用积分方程理论计算了链状分子和团簇在该模型材料中的吸附热力学。其意义在于首次从理论上描述了TMR。第二个目标是将理论描述应用于精心选择的模型单体，模板和吸附物结构，以回答TMR上的重要基本问题。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。的意义将是第一个预测模型的TMR。工业和社会影响：建议的理论描述TMR将是一个有价值的工具，在发展ofnanostructured材料能够高亲和力结合。其合理设计将成为可能的材料的实例包括分子印迹聚合物（MIP）、定向表面组装单分子层、模板官能化无机物和蛋白质模板仿生-这些可以作为传感器、选择性吸附剂和组织工程基底找到重要的应用，并且在成本、鲁棒性和生物相容性方面提供优于常规材料的显著优势，其中真正的生物结构（蛋白质、肽、核酸）被掺入。使用这种描述，可以克服当前的实际问题，例如识别位点的低密度、差的可及性和异质结合强度。此外，这些有机形成的材料在水性环境中发挥作用的能力将得到增强。人们可以想象，未来通过模板进行的纳米结构修饰将被常规地用于为特定的结合应用定制材料。此外，少数民族和妇女将被鼓励参与这所大型城市大学。 最后，计划举办一系列研讨会，要求学生就他们的研究部分进行演讲。

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.