Cardiac cells imaging via non-linear optical techniques: synthesis and spectroscopic characterization of a selected library of quadrupolar dyes

Voltage sensitive dyes are fluorescent potential-sensitive probes extensively used for myocardial contraction mapping. The majority of commercially available probes relies on two mechanisms: electrochromism or photoinduced electron transfer. Despite the great time resolution provided by these systems, they are affected by a low signal to noise ratio. Our aim is to tackle this issue by creating a non-linear optical technique for examining the contraction of cardiomyocytes, providing a four-dimensional resolution encompassing both spatial and temporal dimensions. We decided to use quadrupolar pull-pull fluorescent molecules1 able to stain the phospholipidic bilayer of cardiac cells. These probes operate on a dual mechanism: first, the variation of membrane potential during the cell contraction should result in a different fluorescent response (electrochromism). Second, the presence of an electric field along the molecular axis generates a non-symmetric excited state, resulting in the capability to generate non-linear second order responses, such as second harmonic generation.2 In this poster presentation, we report the synthesis and spectroscopic properties of a selected library of fluorene-based quadrupolar dyes. The central fluorescent core is asymmetrically functionalized exploiting Sonogashira coupling reactions, with two electron-donating arms, one bearing a lipophilic and the other a polar end, to ensure a homogeneous orientation of the probe within the cell membrane.