FACILE SYNTHESIS AND PHYSICAL AND SPECTRAL CHARACTERIZATION OF 2,6-DI-tert-BUTYL-4-NITROPHENOL (DBNP): A POTENTIALLY POWERFUL UNCOUPLER OF OXIDATIVE PHOSPHORYLATION

Abstract

The compound 2,6-di-tert-butyl-4-nitrophenol (DBNP), a potentially powerful uncoupler of ATP-generating oxidative phosphorylation, has been physically and spectroscopically characterized using X-ray crystallography, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), GC-MS spectrometry, Fourier-transformed IR (FTIR) spectrophotometry, UV-Vis spectrophotometry, and FT 'Hand I3C-NMR spectroscopy. However, DBNP is not commercially available; therefore, it had to be synthesized in the laboratory prior to toxicity studies. The DBNP was prepared from 2,6-di-tert-butylphenol (DBP) precursor in hexane through an electrophilic aromatic substitution process using NOz. A collective yield of 75% was obtained by using two empirically determined end points that prevented the coprecipitation of reaction by-products and resulted in the formation of DBNP in high purity. Excessive amounts of NO2 in reaction mixtures resulted in the decomposition of preformed DBNP. With a pK, value of 6.8 and a higher degree of lipophilicity, DBNP may prove to be a stronger uncoupler of oxidative phosphorylation than 2,4-dinitrophenol (pK, = 4.09) due to the expected enhancement of passive-diffusion kinetics across biological membranes at the physiological p H of 7.4. The present study is intended to provide analytical toxicologists, industrial hygiene monitors, and other professionals involved in chemical health and safety with a comprehensive source of basic information on the synthesis and analytical chemistry of DBNP. Keywojds-Synthesis 2,6-Di-tert-butyl-4-nitrophenol

Phenol Oxidation by a Nickel(III)–Fluoride Complex: Exploring the Influence of the Proton Accepting Ligand in PCET Oxidation

“…In the post‐reaction electronic absorption spectra a new band at λ =431 nm for X=CN (Figure S23) and λ =445 nm for X=NO 2 , (Figure S24) was observed. These new bands were tentatively assigned to the corresponding phenolate ions ( X ArO − ) . In fact, we observed that 1 also immediately reacted with 4‐NO 2 ‐2,6‐DTBP to form the corresponding phenolate ion, which showed a band at λ =445 nm (Figure S25).…”

Toxicity of 2,6-Di-tert-butyl-4-Nitrophenol (DBNP)

“…Rivera-Nevares et al reported that DBNP was second only to 3,5-di-tert-butyl-4-hydroxybenzylidene malononitrile in its action as an ATP uncoupler, based on quantum-mechanical calculations. (9) The effects of chronic exposures to DBNP at low concentrations will require further research.…”

The use of 3,3′,4′,5‐tetrachlorosalicylanilide as a chemical uncoupler to reduce activated sludge yield

“…One of the first oxidative uncouplers to be studied was 2,4‐dinitrophenol (DNP). Other uncouplers of early interest were chlorinated and nitrated phenols 6, 7. Recently, it has been reported that 3, 3', 4′, 5‐tetrachlorosalicylanilide (TCS), a component in the formulation of soaps, rinses, and shampoos, etc, can reduce the transfer resistance of the cell membrane for protons, thus upsetting the balance of protons within the cell, resulting in excessive energy use for recovering this balance.…”