Linker‐Free Near‐IR Aza‐BODIPY‐Glutamine Conjugates Through Boron Functionalization

Abstract

A series of linker‐free aza‐BODIPY‐glutamine conjugates were synthesized and investigated, both experimentally and computationally. The structures of the aza‐BODIPYs were confirmed spectroscopically, and in the case of 3a an X‐ray structure was obtained. All aza‐BODIPYs show intense absorption bands between 642–667 nm and fluorescence emissions between 691–703 nm. The fluorescence quantum yields of the 2,6‐unsubstituted compounds 1a–4a were found to be Φf ≈ 0.2 in chloroform, while those of the corresponding 2,6‐dibrominated derivatives 1b–4b were less than 0.01. The cytotoxicity and cellular uptake of all aza‐BODIPYs were investigated in human carcinoma HEp2 cells. The most cytotoxic aza‐BODIPYs were found to be 3a and 3b, due to the presence of the cyclic N,O‐bidentate amino acid ring, rather than the presence of the 2,6‐bromine atoms. The results show that the mode of glutamine conjugation to the aza‐BODIPY determines the stability and cytotoxicity of the conjugates.