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

项目摘要：天然酚类化合物以其独特的抗生素和抗氧化活性而闻名，可用于医疗、制药和工业领域。在本研究中，将选择几种天然酚类化合物作为模型化合物，并将其聚合和交联形成永久的抗生素和抗生物污染涂层。研究其构效关系，提出新的抗生素抗生物污染机制。这些化合物的氧化还原电位（即抗氧化活性）将用于描述可能的新的抗生物污染机制。初步实验表明，模型化合物及其聚合物和涂层具有独特的抗生素和抗生物污垢活性。这些活性被认为可能是由于细胞膜与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穿膜作用的综合作用。氧化还原电位受酚环取代基（如OH和COOH）和酯键控制，认为氧化还原电位干扰了电子传递系统（ETS）和细胞膜酶，从而导致细胞死亡。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外聚合物感应分子（如酰基-高丝氨酸内酯（AHL））之间的相互作用，以验证新的抗生物污垢机制。模型化合物的各种结构将被分离、合成、聚合和表征，以确定构效关系。酶合成的聚合物也将用于形成具有明确结构的聚合物和固体表面的永久抗生物污染涂层。1)所提出的抗生素机制被认为与现有抗生素的机制不同，有望有助于开发减少抗生素耐药性的新抗生素。2)羟基自由基对群体感应分子和膜酶失活的机制是一种新的途径，将为更好地理解抗生物污染的机制和策略提供新的思路。3)可再生资源的酶法聚合是一种精确、环保的过程，与从可再生资源中合成新材料相吻合。3)使用金交叉电极膜和阻抗分析仪测量涂层的氧化还原电位（它也被认为是易于准确测量固体材料抗氧化或促氧化活性的有价值的工具）。更广泛的影响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整合到科学和工程教学中。2)本研究开发的抗生物污涂料高效环保，有望对船舶、导管、食品加工、医疗/牙科设备和配水系统产生重大影响。4)利用交叉指状电极膜和交流阻抗分析仪测量固体涂层的氧化还原电位，可应用于检测环境污染物中低浓度自由基或癌变或肿瘤发生早期的超灵敏生化传感器。

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.