Protective Effect of PEG-EDTA and Its Zinc(II) Complex on Human Cells

The most widely used chelating agent, ethylenediaminetetraacetic acid (EDTA), can cause mild to serious side effects when used for clinical applications. Introducing a polyethylene glycol (PEG) moiety into the molecular structure of EDTA has been shown to lower its toxicity; however, it is unclear whether this could affect EDTA chelation efficiency due to the steric hindrance and the loss of a coordination site caused by the PEGylation reaction. This research aimed to determine if PEGylation could reduce EDTA toxicity without affecting its chelation efficiency. To this end, effective formation constants were determined for EDTA and PEG-EDTA rare earth metal ion complexes using spectrophotometric and titrimetric methods. The stability of PEG-EDTA complexes with the target metal ions was assessed under different conditions using Fourier-transform infrared spectroscopy. The cytotoxicity and metal detoxification capacity of EDTA, PEG-EDTA, and their zinc(II) complexes were determined in two selected human cell types exposed to toxic heavy metal ions. This study suggests that PEG-EDTA has lower toxicity than EDTA, especially when complexed with a nontoxic metal ion, such as zinc(II), while only slightly losing chelation efficiency, potentially making PEG-EDTA a more favourable metal detoxification reagent for clinical applications.