Antimicrobial effect of a new class of light resistant silver(I) complexes Adhesi

描述（由申请人提供）：严重细菌感染的发生是所有植入物插入手术中的严重并发症。它与相当大的发病率和成本有关。这个问题的解决需要开发新的植入材料，其将表现出强的抗微生物活性而对宿主组织没有毒性作用。我们的中心假设是，当用作辅助材料或替代材料时，具有强抗微生物作用的非抗生素、抗UV和抗可见光的银（I）络合物提供了这样的益处。因此，所提出的研究的目标是研究十种新合成的氰肟酸银（I），并检查它们对细菌粘附和生物膜形成的抗微生物作用。这些化合物对强UV和可见光的惰性将允许它们作为添加剂应用于关节置换治疗和牙科植入物插入中所用的光固化聚合物复合材料。由于细菌粘附和生物膜形成是植入物感染发展中的重要诱发因素，因此银（I）络合物对其发展的抑制作用将使得银（I）氰基肟酸盐能够作为新的抗微生物表面应用。 本论文的主要工作是：（1）合成一系列新型的氰肟银（I）配合物，并对其热稳定性进行测试;（2）制备含有不同质量%的银（I）氰肟酸盐的固体聚合物复合材料，并将它们成形为圆柱体和平板，并且还将它们存款成膜沉积到陶瓷和金属的表面上（3）鉴定和定量表征银（I）氰肟酸盐涂覆的表面对铜绿假单胞菌、S.金黄色葡萄球菌和变异人 该研究具有创新性，因为它将是第一个系统和严格的测试新的耐光银（I）配合物对细菌粘附和生物膜形成的抗菌效果。我们希望已经确定了最有效的化合物，可以提供进一步的体内测试。这项研究将对开发新的方法预防人工关节和植入物手术引入引起的细菌感染产生重大影响。 这项研究是化学和微生物学之间的跨学科项目。这将涉及两个机构的两名研究生和三名本科生，并将提供在现代生物无机化学，微生物学和生物医学研究领域的研究和发现过程中的宝贵的“实践”培训。学生在该项目中获得的研究经验将对他们的职业生涯发展产生重大影响。 公共卫生相关性：医疗植入材料的感染是植入物插入的常见并发症，并且与相当大的发病率和成本相关。因此，迫切需要开发能够预防术后感染的新植入物材料。需要这样的化合物来抑制细菌生长，但不对人体组织表现出毒性作用。本研究拟合成一系列新型非抗生素氰肟酸银（I），它们是抗紫外和可见光的化合物，对细菌粘附和生物膜形成具有显著的抗菌作用。这些化合物对紫外线和可见光的耐受性将使它们能够作为关节置换治疗和牙科植入物插入中紫外线辐射可固化聚合物复合材料的添加剂。它们的抗微生物作用将使它们能够应用于预防植入物相关感染，而热稳定性将允许对涂覆的留置装置进行灭菌。 拟议的研究是两个国家机构的化学和微生物学部门之间的跨学科项目。该项目将涉及两名研究生和三名本科生，并将在现代生物无机化学、微生物学和生物医学研究领域的研究和发现过程中提供宝贵的“实践”培训。

DESCRIPTION (provided by applicant): Development of severe bacterial infections is a serious complication in all implant-inserting surgeries. It is associated with considerable morbidity and costs. Solution of this problem requires development of new implant materials that would demonstrate a strong antimicrobial activity without toxic effects on host tissues. Our central hypothesis is that non-antibiotic, UV and visible light resistant silver(I) complexes with strong antimicrobial effect offer such benefits when used either as an adjunct or alternative material. Therefore the goal of the proposed research it to study the ten newly synthesized silver(I) cyanoximates and examine their antimicrobial effect on bacterial adhesion and biofilm formation. Inertness of these compounds towards intense UV and visible light will allow their application as additives to the light curable polymeric composites used in joint replacement therapy and dental implants insertions. Since bacterial adhesion and biofilm formation are important predisposing factors in the development of implant infections, the inhibitory effect of the silver(I) complexes on their development will enable application of the silver(I) cyanoximates as new antimicrobial surfaces. The goal will be achieved by accomplishing the following specific aims: (1) synthesize series of novel silver(I) cyanoximates in sufficient for further studies quantities and test their thermal stability; (2) prepare solid polymeric composites containing different mass % of silver(I) cyanoximates and shape them as cylinders and plates, and also deposit them as films onto the surface of ceramics and metals (Ag, Co, Ni) for further antimicrobial studies; (3) identify and quantitatively characterize the effect of silver(I) cyanoximate-coated surfaces on bacterial adhesion and biofilm formation of P. aeruginosa, S. aureus and S. mutans. The proposed research is innovative since it will be the first systematic and rigorous test of antimicrobial effect of the new light resistant silver(I) complexes on bacterial adhesion and biofilm formation. We expect to have identified the most effective compound that may be offered for further in vivo testing. This study will have a significant impact on the development of new methods of preventing bacterial infections caused by surgical introduction of prosthetic joints and implants. The proposed research is interdisciplinary project between chemistry and microbiology. It will involve two graduate students and three undergraduate students from both institutions, and will provide valuable "hands-on" training in research and discovery process in the areas of modern bio-inorganic chemistry, microbiology and biomedical research. The research experience that students would receive working on the project will significantly impact the development of their professional careers. PUBLIC HEALTH RELEVANCE: Infection of medical implanted materials is a common complication of implant insertions and is associated with considerable morbidity and costs. Therefore there is a critical need for developing new implant materials that would prevent post-surgical infections. Such compounds are required to inhibit bacterial growth, but not to exhibit toxic effect towards human tissues. The proposed research will synthesize a series of new non-antibiotic, silver(I) cyanoximates, which are UV and visible light resistant compounds and exhibit a significant antimicrobial effect on bacterial adhesion and biofilm formation. The resistance of these compounds towards UV and visible light will allow their application as additives to UV-radiation curable polymeric composites in joint replacement therapy and dental implants insertions. Their antimicrobial effect will enable their application in preventing implant associated infections, while thermal stability will allow sterilization of coated indwelling devises. The proposed research is an interdisciplinary project between chemistry and microbiology departments of two state institutions. This project will involve two graduate students and three undergraduate students, and will provide valuable "hands-on" training in research and discovery process in the areas of modern bio-inorganic chemistry, microbiology and biomedical research.