Indole-Based Near Infrared Chromophores as Potential Phototherapeutic Agents

Here we report the effects of net charge on DNA photocleavage by a series of six negative, neutral, and positive near-infrared (NIR) donor-π-acceptor chromophores (D-π-A) each containing an indole donor group attached to a chloroacrylic acid acceptor vs. an analogous positively charged cyanine dye in which the chloroacrylic acid moiety is replaced by a second indole group. UV-visible spectrophotometry was utilized to investigate dye stability and DNA interactions. Competitive DNA binding experiments with pentamidine and methyl green suggest that the neutrally and positively charged dyes may interact with both the minor and major grooves of B-form DNA. Additionally, using radical specific fluorescent probes and chemical additives in microplate experiments, we show that the irradiation of the neutrally and positively charged dyes with a 750 nm LED medical lamp sensitizes the production of DNA damaging Type II singlet oxygen and/or Type I hydroxyl radicals that cleave plasmid DNA in good to high yields (pH 7.0, 10 °C). NIR phototoxicity data of the dyes in E. coli cultured cells will be discussed. Our goal is to develop indole-based chromophores as NIR photosensitizing agents (PS) in photodynamic therapy (PDT).