Synthesis and Characterization of N-Demethylated Metabolites of Malachite Green and Leucomalachite Green

Abstract

Malachite green (MG), a triphenylmethane dye used to treat fungal and protozoan infections in fish, undergoes sequential oxidation to produce various N-demethylated derivatives (monodes-, dides(sym)-, dides(unsym)-, trides-, and tetrades-) both before and after reduction to leucomalachite green (LMG). The close structure resemblance of the metabolites with aromatic amine carcinogens implicates a potential genotoxicity from exposure to MG. The availability of the synthetic standards is important for metabolic and DNA adduct studies of MG. This paper describes a simple and versatile method for the synthesis of MG, LMG, and their N-demethylated metabolites. The synthesis involves a coupling of 4-(dimethylamino)benzophenone or 4-nitrobenzophenone with the aryllithium reagents derived from appropriately substituted 4-bromoaniline derivatives, followed by treatment with HCl in methanol. The resulting cationic MG and their leuco analogues showed systematic UV/vis spectral and tandem mass fragmentation patterns consistent with sequential N-demethylation. The extensive (1)H and (13)C spectral assignments of the metabolites were aided by the availability of (13)C(7)-labeled MG and LMG. The results indicate the existence of a resonance structure with the cationic charge located in the central methane carbon (C(7)). The synthetic procedure is general in scope so that it can be extended to the preparation of N-demethylated metabolites of other structurally related N-methylated triphenylmethane dyes.

Decolourization of Triphenylmethane Dyes and Dye Industry Effluent by Staphylococcus Aureus Isolated From Dye Contaminated Site

“…Because of its low cost, its effectiveness as an antifungal agent for commercial poultry feed and its ready availability, the general public may be exposed to the dye and its metabolites through the consumption of treated poultry products. Basic Violet 3 is a mutagen, a mitotic poison and clastogens possibly responsible for promoting tumour growth in some species of fish [13]. The carcinogenic effects of basic violet 3 in mice and rodents have also been reported [14,15].…”

Removal of Malachite Green Dye From Aqueous Solution Using Multi-Walled Carbon Nanotubes: An Application of Experimental Design

“…MG is easily absorbed by fishes after treatment and reduced in the tissues of fish to its colourless metabolite compound known as leucomalachite green (LMG), which is also a suspected mutagen and teratogen [7]. LMG excretes very slow (t 1/2 ~ 40 days) in certain fatty tissues and this causes the accumulation of LMG in fishes [8]. In addition, MG can cause harm to the aquatic environment; in a way, it is reducing light penetration and photosynthesis [9,10].…”

Activated Carbon Loaded N, S Co-Doped TiO₂ Nanomaterial and its Dye Wastewater Treatment

“…Methyl green (MEG) is used extensively in the fabric industry for dyeing nylon, silk, wool and cotton as well as for colouring of oil, waxes, fats and varnish [18]. The binding of MEG to DNA is possibly ionic, as opposed to intercalative, and it remains so stably bound to double-stranded DNA that, with its modification to the colorless carbinol from, it has been used to evaluate the binding of other molecules to DNA [19,20].…”