Open AccessSynthesis and Operating Optimization of the PEG Conjugate via CuAAC in scCO2
Author(s) -
Sonia López,
Ignacio Gracia,
Juan F. Rodrı́guez,
María Jesús Ramos
Publication year - 2021
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.0c05466
Subject(s) - coumarin , response surface methodology , factorial experiment , dpph , peg ratio , click chemistry , supercritical carbon dioxide , chemistry , polyethylene glycol , supercritical fluid , proton nmr , combinatorial chemistry , organic chemistry , chromatography , antioxidant , economics , statistics , mathematics , finance
A new sustainable green protocol for obtaining polyethylene glycol (PEG) conjugates, with a prototype molecule, which in this work was coumarin, by means of click chemistry is presented. The organic solvents commonly used for this type of reaction were replaced by supercritical carbon dioxide (scCO 2 ). The synthesis and characterization of PEG-coumarin were successfully reported using FTIR, 1 H NMR, and MALDI TOF. Subsequently, a preliminary study was carried out using the response surface methodology to examine the variables that most affect the use of scCO 2 as a reaction medium. The main effects caused by these variables, individually and their binary interaction, have been estimated. The response surface methodology has been used in this work to screen variables using a factorial design 2 3 . The p -values of temperature and pressure were 0.006 and 0.0117, being therefore the most significant variables of the response surface methodology study. Subsequently, a more intensive study has been carried out on the variables that have shown the greatest significant effect on reaction performance where an 82.32% synthesis success was achieved, which broadens the scope of the use of scCO 2 as a reaction medium. The conjugated coumarin with mPEG-alkyne and coumarin were evaluated for their in vitro antioxidant activities by the DPPH radical scavenging assay and were found to exhibit substantial activities. The click product showed comparable or even better efficacy than the initial coumarin.