Comparative triad of routes to an alkyne-BF2 azadipyrromethene near-infrared fluorochrome

Abstract

A series of three inter-related synthetic routes to a water soluble alkyne substituted BF2-azadipyrromethene fluorochrome is described. Each route allows for the introduction of the required reactive alkynyl group and water solubilizing propane-sulfonic acid through either more advanced pyrrole intermediates or through their earlier synthetic precursors. The advantages and disadvantages of each route lie in the number of synthetic steps required versus the formation of undesired azadipyrromethene by-products. Upon its synthesis, the alkyne-bearing fluorochrome was shown to efficiently participate in CuACC reactions with a series of azido substrates in water at room temperature and 37 °C. NIR-photophysical properties of the fluorochrome and its conjugates were similar, showing strong potential for in vitro and in vivo imaging applications.