The Investigation of Configurationally Stable Longitudinally Twisted Acenes and the Development of a Silorane-Based Biomaterial for Use as an Antimicrobial Delivery Device
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Longitudinally twisted acenes (LTAs) adopt a helical twist in order to alleviate steric congestion caused by bulky substituents along the acene backbone and are inherently chiral. As is observed in helicenes, this helical twist gives rise to M and P enantiomers, which may possess theoretically interesting chiroptical properties. In order to study the chiroptical properties of these compounds, they must be configurationally stable. One approach to configurational stability is through the extension of the acene core. Semiempirical calculations at the AM1 level resulted in values that align well with the experimentally determined crystal structure values. DFT calculations generated similar results, albeit with slightly larger differences. Inducing an energetically favored twist bias through the incorporation of bulky naphthyl groups in a dissymmetric fashion is an alternative approach to configurationally stable compounds. A twist bias was observed for all naphthyl substituted compounds. From this study, it is apparent that the twist bias is not directly proportional to the overall twist and is affected by many factors, including sterics. The number of joint replacement procedures is expected to rise exponentially over the next few decades. As with any surgery, a number of complications can occur including prosthetic joint infection (PJI), an infection of the surrounding bone and tissues. These risks are further compounded when presented with additional risk factors including previous joint infections, obesity, and diabetes. PJI affects approximately 2% of all primary hip and knee replacements, but increases to 15.8% for multiple replacements/revisions. Treatment options are limited to heat and chemically stable antimicrobials due to the composition and curing temperatures (>70 °C) of commercially available poly(methyl methacrylate) (PMMA) bone cements. With the number of antibiotic and antifungal resistant pathogens on the rise, it is pertinent to expand the number of antimicrobials that can be incorporated into and eluted from bone cement. We have developed a novel silorane-based biomaterial that has the potential to serve as a delivery device for a breadth of antimicrobials including those unsuited for use in PMMA while displaying none of the drawbacks typical of commercial bone cements The silorane-based biomaterial exhibits a lower exotherm (~26 °C), is non-toxic, has less shrinkage, and maintains comparable mechanical strength to commercial PMMA bone cements in vitro and in vivo. PMMA compatible and incompatible antimicrobials have been incorporated into silorane bone cement. The elution profiles and the effect of incorporation on the retention of antimicrobial activity and mechanical properties were measured. Our preliminary results have demonstrated the ability of silorane to serve as an antimicrobial delivery device.
Table of Contents
Investigation of Configurationally Stable Longitudinally Twisted Acenes -- Development of a Silorane-based Biomaterial -- Silorane-based Biomaterial as an antimicrobial Delivery Device -- Summary -- Future Work -- Materials and Methods
Ph.D. (Doctor of Philosophy)