Synthesis and characterization of triblock poly(ethylene glycol)-b-[poly(lactide-co-serine-nh2)] polymers

The aim of this study was to synthesize PLDSNH2-PEG-PLDSNH2 block copolymers in three stages. Firstly, LDS, LD2S, and LD3S monomers were synthesized by reacting Boc-serine-OH amino acid with lactide, heated at 95°C for 15-30 hours. FT-IR spectra of the LDS monomers showed stretching bands for methyl, methylene, and methine groups (3000-2800 cm-1). Active hydrogen stretching bands for urethane, hydroxyl, and carboxylic acid groups were observed (3500-2500 cm-1). Three carbonyl groups (ester, carboxylic acid, and urethane) were identified at 1736, 1720, and 1690 cm-1. The presence of tert-butoxycarbonyl protection group was confirmed by (tert-butoxycarbonyl) methyl bending vibrations. The 1H-NMR spectrum of the LDS monomers revealed proton peaks corresponding to the tert-butoxycarbonyl protection group OC(CH3)3 at 1.47 ppm and lactide methyl protons at 1.60 ppm chemical shift values. The shifting of methylene protons in the range of 4.00-3.70 ppm confirmed the ester formation between the lactide ring and the hydroxyl group of serine. Protons from the urethane group and the methine proton =CH-NH- of the LDS monomer were observed at chemical shift values of 5.67 and 3.40 ppm, respectively. The broad signal in the 5.10-5.50 ppm chemical shift range indicated the presence of lactic acid repeating units in the LDS monomer, which can occur due to both end and ester group attachment on the chain, as well as the presence of multiple lactide units such as LD2S and LD3S. MALDI-TOF-MS analysis showed binding of one to three lactides to Boc-serine, forming LDS, LD2S, and LD3S monomers. Boc-serine's molecular weight was 205.11 g/mol, lactide was 144.13 g/mol, and sodium was 22.99 g/mol, totaling 372.23 g/mol. The LDS monomer spectrum exhibited an observed m/z value of 372.244, corresponding to its theoretical molecular weight. LD2S monomer's theoretical molecular weight was 516.36 g/mol, and the observed m/z value was 516.201. After the completion of LDS monomer synthesis, the study focused on the synthesis of poly(lactide-co-serine) (PLDS) copolymers. Using LDS15 and LDS30 monomers obtained by varying the reaction time, PLDS15 and PLDS30 copolymers were synthesized through DCC polymerization. The MALDI-TOF-MS spectra of PLDS samples showed positive ion peaks in the mass range of 700-1700 m/z, indicating the presence of oligomers. The predominant units in the PLDS15 and PLDS30 polymers were identified as LDS and LD2S monomers. The highest molecular weight peaks observed in the spectra were determined to belong to specific polymer structures, with 1408 m/z corresponding to DL3S5 and 1696 m/z corresponding to DL5S5. The studies on PEG-b-PLDS block copolymers were conducted using PEG-diacid (PEGDA) with carboxyl end groups or PEG-diol (PEGDO) with hydroxyl end groups. The characterization of the PLDS-PEG-PLDS block copolymer was performed through MALDI-MS, FTIR, and 1H-NMR studies. In the final stage, the protected amine side groups of the PLDS-PEG-PLDS block copolymer were removed using nitric acid, resulting in the synthesis of a block copolymer with consecutive amine side groups, known as PLDSAm-PEG-PLDSAm. This synthesis allowed for the incorporation of consecutive amine side groups in the polymer main chain, representing a novel approach with potential new applications and functionalities.