Natural Resin Acid-Containing Antimicrobial BioMaterials: Synthesis and Mechanism

ID：MPS/DMR/BMAT(7623)1206072 PI：唐，传兵ORG：南卡罗来纳大学标题：天然树脂酸抗菌剂生物材料：合成和机理电子优点：细菌感染仍然是导致局部组织破坏、患者残疾、发病率和死亡的最严重的并发症之一。该项目寻求开发低成本的生物材料和抗菌剂，以杀死广泛的细菌，但对哺乳动物细胞的毒性较低。有人提出，天然树脂酸基阳离子材料可以大量合成，成本低，可以作为坚固的、选择性的抗菌剂来治疗各种细菌感染，或者加入到塑料中，如用于医疗导管的塑料中。初步数据显示，当天然树脂酸化学修饰为酸基阳离子化合物和聚合物时，可以有效地抑制多种革兰氏阳性和革兰氏阴性细菌的生长，而不会导致显著的红细胞溶血。PI将通过精确的分子和大分子设计展示具有可控电荷位置、电荷密度、平衡疏水性和独特构象的树脂酸基阳离子化合物和聚合物的多功能性。该项目将结合荧光显微镜/光谱学和原子分子动力学建模来研究这些材料与细菌膜之间的相互作用。这些独特的材料将被配制成以钛和聚合物为基础的医疗植入物上的抗菌涂层。最终目标是将树脂、酸基阳离子化合物和聚合物最理想和最独特的特性转化为具有当前抗菌材料前所未有的功能和性能的新型抗菌剂。更广泛的影响：与细菌污染相关的感染是全球医疗保健中的一个关键问题。这一建议不仅通过前所未有的化学和聚合技术的使用促进了对树脂酸的认识，而且还揭示了将疏水性树脂酸用作抗菌剂中的活性成分的新概念。本文提出的研究将对减少细菌感染的不断升级的发生产生积极影响。拟议的调查涉及合成有机和聚合物化学、微生物学和生物医学等领域。这项提案的技术性质将为研究生和本科生提供聚合物合成和抗菌剂方面的培训机会。上述计划的一个重要组成部分是针对高中生、本科生和研究生的几项综合教育活动，以增加全球研究和教育培训机会，激发他们对科学技术的兴趣。将与一家中国机构开展可持续材料和纳米技术教育的国际推广计划，以促进在解决自然产品利用和全球医疗保健方面的全球合作/网络，并加强美国学生的国际能力和竞争力。此外，该项目将参与ACS SEED计划，以支持来自经济困难背景的高中生的暑期研究机会。与历史悠久的黑人学院和大学的现有合作将继续培养非裔美国本科生。最后，十多年前通过国家科学基金会资助发起的青年科学家计划将在当地中小学继续开展。

ID: MPS/DMR/BMAT(7623) 1206072 PI: Tang, Chuanbing ORG: University of South CarolinaTitle: Natural Resin Acid-Containing Antimicrobial BioMaterials: Synthesis and MechanismINTELLECTUAL MERIT: Bacterial infections remain one of the most serious complications leading to destruction of local tissues, patient disability, morbidity, and death. This project seeks to develop low-cost biomaterials and antimicrobial agents that kill a broad spectrum of bacteria, but present low toxicity to mammalian cells. It is proposed that natural resin acid-based cationic materials, which can be synthesized in large quantities and at low cost, can be used as robust, selective antimicrobial agents to treat various bacterial infections or incorporated into plastics such as those used in medical catheters. Preliminary data show that natural resin acids, when chemically-modified to acid-derived cationic compounds and polymers, efficiently inhibit growth of a wide range of Gram-positive and Gram-negative bacteria, without inducing significant hemolysis of red blood cells. The PI will demonstrate the versatility of resin acid-derived cationic compounds and polymers with controlled charge location, charge density, balanced hydrophobicity, and unique conformation via precise molecular and macromolecular design. The project will combine fluorescence microscopy/spectroscopy and atomistic molecular dynamics modeling to study interactions between these materials and bacterial membranes. These unique materials will be formulated into antimicrobial coatings on medical implants based on titanium and polymers. The ultimate goal is to translate the most desirable and unique properties of resin acid-based cationic compounds and polymers into new classes of antimicrobial agents with functionality and performance that are unprecedented for current antimicrobial materials. BROADER IMPACTS: Infections associated with bacterial contamination are a critical issue in global healthcare. This proposal advances not only the knowledge of resin acids via the unprecedented use of chemistry and polymerization techniques, but also uncovers new concepts for utilizing hydrophobic resin acids as active components in antimicrobial agents. The research proposed herein will have a positive impact on reducing the escalating occurrences of bacterial infection. The proposed investigations cut across the fields of synthetic organic and polymer chemistry, microbiology, and biomedicine. The technical nature of this proposal will provide training opportunities for graduate and undergraduate students in polymer synthesis and antimicrobials. An important component of the above plan involves several integrated educational activities for high school, undergraduate, and graduate students to stimulate their interest in science and technology with enhanced global research and education training opportunities. An international outreach program for Education in Sustainable Materials and Nanotechnologies will be pursued with a Chinese institution to facilitate global cooperation/networking in addressing natural product utilization and global healthcare and to strengthen the international competence and competitiveness of American students. Furthermore, the project will participate in the ACS Seed program to support summer research opportunities for high school students from economically disadvantaged backgrounds. Existing collaborations with Historically Black Colleges and Universities will continue to train African American undergraduate students. Finally, a Young Scientist Program, which was initiated over a decade ago through NSF funding, will be continued at local Primary and Middle schools.