INTELLECTUAL 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.
