Thivierge, Cliferson (2011-05). Design and Syntheses of Dyes for Biological Applications. Doctoral Dissertation. Thesis uri icon

abstract

  • The challenges in modern biological imaging applications are two-fold: (i) to develop better methods of imaging, and (ii) develop dyes that are suitable for these methods. This dissertation deals with the design and synthesis of dyes mainly by modification of known dyes to make them suitable for modern biological applications. Towards this aim, novel ways of derivatizing BODIPY dyes are explored. One method involves extending the conjugation via phenyl acetylene units, pushing fluorescence wavelengths near 600 nm. A different approach deals with C-H functionalization of BODIPY in which the fluors are functionalized with acrylate units, extending their fluorescence to the red. The BODIPY dyes developed are then incorporated in through-bond energy transfer cassettes. We examine the factors affecting energy transfer efficiencies by synthesizing analogs of the cassettes and also studying the electrochemical behavior of the donor and acceptor parts. The concept of through-bond energy transfer is incorporated into conjugated polymers by random incorporation of BODIPY dyes into polyfluorenes. The ideal ratio of fluorene to BODIPY parts was found to be 4:1. The BODIPY doping agents result in dispersed emissions when excited the polyfluorene polymers. Concurrently, the polyfluorene backbone acts as an energy harvester for the BODIPY dyes, in effect increasing their molar absorptivities. Finally the use of BODIPY dyes as photodynamic therapeutic agents was examined. We found that BODIPY dyes are efficient at producing reactive oxygen species when halogens are attached directly on the BODIPY core. Furthermore, the mechanism of cell death by using such agents was elucidated. Attachment of the most promising agent to polyglutamic acid is done to promote the EPR effect. Lastly we develop a potentially new type of PDT agent that absorbs strongly above 800 nm, permitting its use in deep tissue PDT.
  • The challenges in modern biological imaging applications are two-fold: (i) to develop better methods of imaging, and (ii) develop dyes that are suitable for these methods. This dissertation deals with the design and synthesis of dyes mainly by modification of known dyes to make them suitable for modern biological applications.
    Towards this aim, novel ways of derivatizing BODIPY dyes are explored. One method involves extending the conjugation via phenyl acetylene units, pushing fluorescence wavelengths near 600 nm. A different approach deals with C-H functionalization of BODIPY in which the fluors are functionalized with acrylate units, extending their fluorescence to the red. The BODIPY dyes developed are then incorporated in through-bond energy transfer cassettes. We examine the factors affecting energy transfer efficiencies by synthesizing analogs of the cassettes and also studying the electrochemical behavior of the donor and acceptor parts.
    The concept of through-bond energy transfer is incorporated into conjugated polymers by random incorporation of BODIPY dyes into polyfluorenes. The ideal ratio of fluorene to BODIPY parts was found to be 4:1. The BODIPY doping agents result in dispersed emissions when excited the polyfluorene polymers. Concurrently, the polyfluorene backbone acts as an energy harvester for the BODIPY dyes, in effect increasing their molar absorptivities.
    Finally the use of BODIPY dyes as photodynamic therapeutic agents was examined. We found that BODIPY dyes are efficient at producing reactive oxygen species when halogens are attached directly on the BODIPY core. Furthermore, the mechanism of cell death by using such agents was elucidated. Attachment of the most promising agent to polyglutamic acid is done to promote the EPR effect. Lastly we develop a potentially new type of PDT agent that absorbs strongly above 800 nm, permitting its use in deep tissue PDT.

publication date

  • May 2011