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

**Authors:** Tashneet Dhaliwal, Cole Babcock, Brynmar Degenhardt, Isaac Osorio Passos, Tigran Stepanyan, Makan Golizeh

PMC · DOI: 10.3390/ijms27010044 · International Journal of Molecular Sciences · 2025-12-20

## TL;DR

This study shows that PEG-EDTA, especially when combined with zinc, is less toxic than EDTA while still effectively removing harmful metals from human cells.

## Contribution

The study demonstrates that PEGylation reduces EDTA toxicity without significantly compromising chelation efficiency.

## Key findings

- PEG-EDTA has lower cytotoxicity than EDTA in human cells.
- PEG-EDTA retains high chelation efficiency for metal ions.
- Zinc(II) complexation enhances the detoxification potential of PEG-EDTA.

## Abstract

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.

## Linked entities

- **Chemicals:** EDTA (PubChem CID 6049), zinc(II) (PubChem CID 32051)

## Full-text entities

- **Diseases:** cytotoxicity (MESH:D064420)
- **Chemicals:** Zinc(II) (MESH:D015032), PEG-EDTA (-), PEG (MESH:D011092), EDTA (MESH:D004492), metal (MESH:D008670), heavy metal (MESH:D019216)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12785647/full.md

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Source: https://tomesphere.com/paper/PMC12785647