Polyacetals: Water-Soluble, pH-Degradable Polymers with Remarkable Thermoresponsive Behavior

非技术概要：近年来，聚合物应用的基本性质发生了显著变化。虽然早期的应用要求聚合物坚固轻便，耐化学品和环境惰性，但今天的应用需要智能聚合物，可以根据一系列不同的外部刺激有效地收缩、膨胀、增厚或改变其材料特性。随着温度的变化，热响应性聚合物在某些物理性质（通常是溶解度）上表现出剧烈而不连续的变化。提出的研究重点是开发一个令人兴奋的热响应性聚缩醛聚合物新家族，具有卓越的性能，非常适合无数的生物医学和其他应用。新的聚缩醛是第一个水溶性热敏聚合物本质上是可生物降解的。它们的热转变可以从它们的分子结构中预测出来，并在大约6-80°C的范围内进行高精度调整，它们具有生物相容性，并且它们在酸性条件下降解形成中性降解产物，不会在体内引起炎症。新的聚缩醛材料具有广泛应用于各种技术的潜力，这些技术不仅在经济上很重要，而且影响生活质量，特别是与医学有关的技术。这种结果的一个例子可能是开发聚缩醛作为治疗胰腺癌的潜在药物递送载体。人员发展是拟议研究的一个重要成果，包括培训和指导博士后研究人员在学术界的职位，包括硕士生参加一个创新的新项目，为本科科学专业的学生提供获得工程硕士学位的机会，并发展本科生的研究技能。参与这项研究的人员还将通过与执业医学临床医生的合作，获得对关键生物医学问题的重要见解。技术概述：主要的技术研究目标是开发聚缩醛材料作为一个新的家族的温度响应，pH可降解的聚合物；并探索其显著的低临界溶液温度（LCST）行为的根本起源，与聚合物重复单元中碳和氧原子的数量成线性比例。将对LCST相图进行建模，以提取相互作用参数的浓度和温度依赖性，从而探索独特温度响应的基本来源。该研究计划还寻求扩大可用的聚缩醛的数量，以满足当前和未来对多刺激响应聚合物的需求。扩展包括探索几种新型单体，开发具有主链功能的单体来接枝感兴趣的功能部分，以及制备具有末端叠氮化物和炔基的大单体，这些大单体可以通过点击化学偶联在一起。大单体能够制备双反应凝胶和嵌段共聚物，可用于重要应用，从用于癌症治疗的智能药物输送载体，在酸性肿瘤中生物降解，到用于农药控制释放的聚合物，在与土壤接触时缓慢降解。研究计划包括模拟显著的LCST行为，以了解其与分子结构的线性依赖关系，以及将嵌段共聚物临界胶束浓度和ph依赖性降解率等其他重要性质与分子结构相关联。成功的建模将提供预测热响应和物理行为的能力，从而可以预先设计这些卓越的新型聚缩醛基材料的性能，以满足特定应用的需求。

NON-TECHNICAL SUMMARY: The fundamental nature of polymer applications has changed markedly over the years. While early applications called for polymers that were strong and light, resistant to chemicals and environmentally inert, today's applications demand smart polymers that can shrink, expand, thicken, or change effectively their material properties in response to a host of different external stimuli. Thermally responsive polymers exhibit a drastic and discontinuous change in some physical property, usually solubility, with change in temperature. The proposed research focuses on the development of an exciting new family of thermoresponsive polyacetal polymers with remarkable properties that are well suited to a myriad of biomedical and other applications. The new polyacetals are the first water-soluble thermoresponsive polymers to be intrinsically biodegradable. Their thermal transitions can be predicted from their molecular structure and tuned to high precision anywhere within a range of about 6-80°C, they are biocompatible, and they degrade under acidic conditions to form neutral degradation products that do not cause inflammation inside the body. The new polyacetal materials have the potential to be used in a broad range of technologies that are important not only economically, but that affect the quality of life, in particular those relating to medicine. An example of such an outcome might be development of polyacetals as potential drug delivery vehicles for the treatment of pancreatic cancer.Personnel development is an important outcome of the proposed research, and involves training and mentoring of a postdoctoral researcher for a position in academia, involving Master's students enrolled in an innovative new program that provides undergraduate science majors the opportunity to obtain a Master's degree in engineering, and developing the research skills of an undergraduate student. The personnel involved with this research will also gain important insight into critical biomedical problems through collaborations with practicing medical clinicians.TECHNICAL SUMMARY: The main technical research objectives are to develop the polyacetal materials as a new family of temperature-responsive, pH degradable polymers; and to explore the fundamental origins of their remarkable lower critical solution temperature (LCST) behavior, scaling linearly with the number of carbon and oxygen atoms in the polymer repeat units. LCST phase diagrams will be modeled to extract the concentration and temperature dependence of the interaction parameter and thereby explore the fundamental origin of the unique temperature response. The research plan also seeks to extend the number of polyacetals available to meet current and future needs for multi-stimuli-responsive polymers. Extensions include exploring several new types of monomers, developing monomers that provide main chain functionality to graft functional moieties of interest and preparing macromonomers with terminal azide and alkyne groups that can be coupled together by click chemistry. The macromonomers enable preparation of dual responsive gels and block copolymers that can be used in important applications ranging from smart drug delivery vehicles for cancer treatment that biodegrade in acidic tumors, to polymers for controlled release of pesticides that slowly degrade upon contact with soil. The research plan includes modeling the remarkable LCST behavior in order to understand its linear dependence on molecular structure, as well as correlating other important properties such as the block copolymer critical micelle concentration and pH-dependant degradation rates with the molecular structure. Successful modeling will provide the ability to predict thermal response and physical behavior so that the properties of these remarkable new polyacetal-based materials can be designed a priori to meet the needs of specific applications.