Structural Insights into Low-Temperature Copolymerization of Thermodegradable Amino Acids Mediated by Pyroglutamic Acid

The demand for biocompatible multifunctional systems for bioimaging is driving the interest in new-generation fluorescent peptide based on nonaromatic amino acids such as l-glutamic acid and l-alanine. In general, due to the high melting points characterizing the zwitterionic structures of amino acids, their thermal polymerization is performed at temperatures between 200 and 300 °C. However, in this range of temperatures, most of the amino acids tend to decompose rather than undergo polymerization. The present work shows how to obtain nonaromatic fluorescent peptides at temperatures as low as 160 °C by copolymerizing l-glutamic acid with other high-melting amino acids, such as l-alanine, l-valine, and l-leucine. The low-temperature conversion of l-glutamic acid into pyroglutamic acid and its copolymerization with another amino acid were fully characterized by infrared and NMR spectroscopies, MS spectrometry, and thermal analysis. The reaction is mediated by the in situ transformation of l-glutamic acid into pyroglutamic acid, which acts simultaneously as an inomer, initiator + monomer, as well as a dispersing agent, allowing copolymerization with another amino acid. The resulting peptides exhibit fluorescent emission in the visible range typical of PGA derivatives, but they also possess a different polar nature that is inherited by the side chain of the second amino acid.