López Sonia, Gracia Ignacio, García María Teresa, Rodríguez Juan Francisco, Ramos María Jesús
Institute of Chemical and Environmental Technology (ITQUIMA), Department of Chemical Engineering, University of Castilla-La Mancha, Avda. Camilo José Cela 1, 13071 Ciudad Real, Spain.
ACS Omega. 2021 Feb 25;6(9):6163-6171. doi: 10.1021/acsomega.0c05466. eCollection 2021 Mar 9.
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). The synthesis and characterization of PEG-coumarin were successfully reported using FTIR, 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 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. The -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 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.
本文提出了一种新的可持续绿色方案，通过点击化学获得聚乙二醇（PEG）缀合物，其原型分子在本工作中为香豆素。此类反应常用的有机溶剂被超临界二氧化碳（scCO₂）取代。使用傅里叶变换红外光谱（FTIR）、核磁共振氢谱（¹H NMR）和基质辅助激光解吸电离飞行时间质谱（MALDI TOF）成功报道了PEG-香豆素的合成与表征。随后，采用响应面法进行了初步研究，以考察对使用scCO₂作为反应介质影响最大的变量。估计了这些变量单独以及它们的二元相互作用所产生的主要影响。本工作中使用响应面法通过析因设计2来筛选变量。温度和压力的p值分别为0.006和0.0117，因此是响应面法研究中最显著的变量。随后，对那些对反应性能显示出最大显著影响的变量进行了更深入的研究，在此研究中实现了82.32%的合成成功率，这拓宽了scCO₂作为反应介质的使用范围。通过DPPH自由基清除试验评估了与甲氧基聚乙二醇-炔烃共轭的香豆素和香豆素的体外抗氧化活性，发现它们具有显著活性。点击产物显示出与初始香豆素相当甚至更好的效果。
