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

描述（由申请人提供）：严重的细菌感染是所有种植体植入手术的严重并发症。它与相当高的发病率和成本有关。解决这个问题需要开发新的植入材料，这些材料将显示出强大的抗菌活性，而不会对宿主组织产生毒性作用。我们的中心假设是，非抗生素、抗紫外线和可见光的银(I)配合物具有很强的抗菌作用，当用作辅助材料或替代材料时，可以提供这样的好处。因此，本文拟对新合成的10种氰化肟酸银进行研究，考察其对细菌粘附和生物膜形成的抑菌作用。这些化合物对强紫外线和可见光的惰性将允许它们作为添加剂应用于光固化聚合物复合材料中，用于关节替代治疗和牙科植入物插入。由于细菌的粘附和生物膜的形成是种植体感染发展的重要诱发因素，银(I)配合物对其发展的抑制作用将使银(I)氰肟酸盐作为新的抗菌表面得到应用。该目标将通过实现以下具体目标来实现：(1)合成一系列新的银(I)氰肟酸酯，以供进一步研究的数量和测试其热稳定性；(2)制备含有不同质量%的氰酸银(I)的固体聚合物复合材料，并将其成型为圆柱体和板，并将其作为薄膜沉积在陶瓷和金属（Ag, Co, Ni）表面，用于进一步的抗菌研究；(3)鉴定并定量表征氰酸银涂层表面对铜绿假单胞菌、金黄色葡萄球菌和变形葡萄球菌细菌粘附和生物膜形成的影响。拟议的研究具有创新性，因为它将是首次系统和严格地测试新型耐光银(I)配合物对细菌粘附和生物膜形成的抗菌作用。我们期望已经确定了最有效的化合物，可以提供进一步的体内试验。这项研究将对预防手术引入假体关节和植入物引起的细菌感染的新方法的发展产生重大影响。拟议的研究是化学和微生物学之间的跨学科项目。该项目将涉及两所院校的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。学生将在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。

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.