Eco-Friendly Synthesis of Acetoguanamine Crown Ethers, Determination of Antioxidant and DNA Damage-Protection Properties

Abstract

Crown ethers are commonly used for metal complexation due to their affinity for cations. These compounds have a hydrophobic outer cavity and a hydrophilic inner cavity. They show an interest in various elemental ions depending on the number, proportions, and diversity of functional groups and donor atoms. The research focuses on synthesizing and characterizing compounds containing different heteroatom-containing groups on the side group, and the investigation of antioxidant and DNA damage-protection properties. Acetoguanamine (2,4-diamino-6-methyl-1,3,5-triazine), a heterocyclic compound that belongs to the triazine class and acts as an intermediate in numerous pharmaceuticals, was synthesized in this study as a crown ether derivative. This was achieved using the SN2 mechanism of 2,4-diamino-6-methyl-1,3,5-triazine and poly(ethylene) glycol dihalides. The reaction utilized a basic catalyst (Cs2CO3) and a microwave-assisted synthesis method. The targeted acetoguanamine crown ether derivatives were synthesized using green chemistry's eco-friendly (microwave-assisted synthesis) method in mild conditions, with quite high yields. After purification, the synthesized macrocyclic 2,4-diamino-6-methyl-1,3,5-triazine crown ether derivatives were characterized structurally using Fourier-Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), and tandem mass spectrometry - Liquid Chromatography (LC-MS/MS) methods. The synthesized compounds were investigated for their antioxidant and DNA damage-protective properties. Experimental tests showed that among the compounds, only S1 exhibited a radical scavenging effect (mean 5.62%), and none of the compounds affected the applied DNA plasmid, or demonstrated a DNA protection effect.