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 (scCO2). The synthesis and characterization
of PEG-coumarin were successfully reported using FTIR, 1H 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 scCO2 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
23. 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 scCO2 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.