Fluorescent histidine-derived biodynamers as biocompatible and highly water-soluble copper(ii)-sensors†

Amino-acid derived biodynamers, characterized as dynamic biopolymers, are synthesized under acidic pH conditions through dynamic covalent chemistry (DCC) between amino acid hydrazides and carbazole hexaethylene glycols (CA-HG). In the field of biomedical research, especially for the designs of smart drug delivery systems, DCC has increasingly gained popularity within the last years. Biodynamers possess a range of advantageous properties, such as fluorescence, tunability through amino acid monomer exchange, water solubility, and biocompatibility. These characteristics make them promising materials for a variety of biomedical applications. By leveraging these beneficial traits, biodynamers can be applied as detectors for physiologically important metal ions, utilizing changes in their fluorescence emission upon binding to the DCC framework and polymer's side chains. In this study, we investigated the potential of histidine-based biodynamers (HisBD) for detecting a key biomarker, Cu(II), using in silico simulations and cuvette assays. Our results revealed that HisBD exhibited selective fluorescence in the presence of Cu(II), with approximately 90% quenching of fluorescence due to binding site interactions and side chain effects under physiological conditions. This study broadens the applications of DCC and underscores the potential of HisBD as a candidate for Cu(II) chemosensors, overcoming the limitations of current systems such as limited solubility, sensitivity, and biocompatibility.