Executive Summary : | Push-pull chromophores, resulting from the click type [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction between electron-rich alkynes and electron-deficient alkenes, are an efficient method for creating nonplanar 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs) based donor-acceptor (D–A) chromophores in molecular and polymeric platforms. These chromophores have gained attention due to their opto-electronic properties, high solubility, and application in organic electronics. However, their use in synthesis of molecular drug analogs and biological applications has been hindered by insoluble substrates and products in aqueous solvents. This challenge can be overcome using micellar chemistry (nanoreactors), which increase the turnover of water systems and produce different reactivity. The effects of various parameters can be evaluated to identify ideal conditions and ensembles for the [2+2] CA-RE reaction in water to produce TCBDs or other heterocycles. Ensembles of transformed surfactants can accelerate post-cycloaddition reactions in polar media by introducing new reactivity. For example, in an amphiphilic system under thermal or microwave heating, one of the donor-connected nitriles was found to undergo water addition, producing 5 or 6-membered heterocycles analogs of cardiotonic drugs amrinone and milrinone. These drugs are proven to treat many diseases and are being tested for their efficacy against these diseases. Establishing a series of derivatives will offer a new method for making such drug candidates. The research aims to obtain TCBDs in water as substitutes for organic solvent-mediated chemistry and focus on using this result in biological applications. This unique approach in [2+2] CA-RE click reactions may open new doors for its exploitation in drug discovery. |