A Novel Approach to Antibiotic and Anti-biofouling Activities of Natural Phenols

项目摘要天然酚类化合物具有独特的抗菌和抗氧化活性，可用于医疗、制药和工业应用。本研究将以几种天然酚类化合物为模型化合物，通过聚合和交联反应形成永久性的抗菌防污涂料。我们将研究这些化合物的构效关系，并提出新的抗生素抗生物污损机制。这些化合物的氧化还原电位(即抗氧化活性)将被用来描述可能的新的抗生物污垢机制。初步实验表明，这些模型化合物及其聚合物和涂层具有独特的抗菌和抗生物污垢活性。这些活性被认为是由于细胞膜和酚类化合物之间的强氧化还原电位和氢键以及长烷基链的膜穿透效应的综合作用。氧化还原电位受酚环取代基如OH、COOH和酯键的控制，电子传递系统(ETS)和细胞膜酶被认为受到氧化还原电位的干扰，导致细胞死亡。对于涂层的抗生物污垢活性，将研究酚类化合物与微生物的胞外聚合物诱导的传感分子之间的相互作用，例如酰基高丝氨酸内酯(AHL)，以验证新的抗生物污垢机理。模型化合物的各种结构将被分离、合成、聚合和表征，以确定结构-活性关系。酶法合成的聚合物还将用于在固体表面形成具有明确结构和永久防生物污损涂层的聚合物。1)所提出的抗生素机制被认为不同于现有抗生素的机制，并有望有助于开发降低抗生素耐药性的新抗生素。2)提出的羟基自由基灭活群体感应分子和细胞膜酶的机制是一种新的方法，将为更好地理解生物污染的机制和策略提供依据。3)可再生资源的酶促聚合是一种精确的、环境友好的聚合过程，与利用可再生资源合成新材料相吻合。3)将使用金交指电极膜和阻抗分析仪测量涂层的氧化还原电位(它也被认为是简单而准确地测量固体材料的抗氧化性或促氧化活性的宝贵工具)。广泛影响1)来自代表性不足地区的本科生和当地高中生将参与该项目，以便在更广泛的层面上将研究活动融入理工科教学。2)本研究开发的防生物污损涂料是高效和环保的，预计将对船舶、导管、食品加工机、医疗/牙科设备和供水系统产生重大影响。4)用交指电极膜和交流阻抗分析仪测量固体涂层的氧化还原电位，可应用于超灵敏生化传感器，用于检测环境污染物中的低浓度自由基或在致癌或致癌的早期阶段。

ABSTRACTPI: Dong-Shik Kim and Xuefei Huang Institution: University of ToledoProposal Number: 0626022Title: A Novel Approach to Antibiotic and Anti-biofouling Activities of Natural PhenolsProject SummaryNatural phenolic compounds are known for unique antibiotic and antioxidant activities that can be used for medical, pharmaceutical, and industrial applications. In this research, several natural phenolic compounds will be selected as model compounds, and will be polymerized and crosslinked to form permanent antibiotic and anti-biofouling coatings. The structure-activity relationships will be investigated, and novel antibiotic anti-biofouling mechanisms will be suggested. The redox potential (i.e., antioxidant activity) of these compounds will be used to delineate possible new anti-biofouling mechanisms.Preliminary experiments show unique antibiotic and anti-biofouling activities of the model compounds and their polymers and coatings. These activities are thought to be possible by a combinatory effect of strong redox potential and hydrogen bonding between the cell membranes and phenolic compounds as well as the long alkyl chains membrane penetrating effect. The redox potential is controlled by the phenol ring substituents such as OH and COOH, and ester-linkage, and it is thought that the electron transport system (ETS) and cellular membrane enzymes are disturbed by redox potential, which leads to cell death. For the anti-biofouling activity of the coating, the interaction between the phenolic compound and exopolymer-inducing sensing molecules of the microbes, e.g., acyl-homoserine lactone (AHL), will be investigated to verify the novel anti-biofouling mechanisms. Various structures of the model compounds will be separated, synthesized, polymerized and characterized to determine the structure-activity relationship. The enzymatically synthesized polymers will also be used to form polymers with well-defined structures and permanent anti-biofouling coating on the solid surface.Intellectual Merit1) The suggested antibiotic mechanisms are thought to be different from those of existing antibiotics, and expected to contribute to development of new antibiotics that reduce antibiotic resistance. 2) The suggested mechanisms of deactivation of quorum sensing molecules and membrane enzymes by hydroxyl radicals are a novel approach that will provide a better understanding on anti-biofouling mechanisms and strategies. 3) Enzymatic polymerization of the renewable resources is a precise and environmentally benign process that dovetails with synthesis of new materials from renewable resources. 3) Measuring redox potential of the coating using a gold interdigitated electrode film and impedance analyzer will be used (it is also considered a valuable tool for easy and accurate measurement of anti- or prooxidant activity of solid materials).Broader Impacts1) Undergraduate students and local high school students from underrepresented areas will participate in the project in order to integrate research activities into the teaching of science and engineering at broader levels. 2) The anti-biofouling coatings developed in this study are efficient and environmentally-benign, and expected to make significant impacts on ships, catheters, food processors, medical/dental devices, and water distribution systems. 4) Measurement of the redox potential of solid coating by using an interdigitated electrode film and ac impedance analyzer can be applied to ultra-sensitive biochemical sensors for detecting low concentrations of free radicals in environmental pollutants or in the early stage of carcinogenesis or tumorigenesis.