2,4-Dinitrophenol (
DNP),
CCarbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
6HHydrogen is the chemical element with atomic number 1. It is represented by the symbol H. At standard temperature and pressure, hydrogen is a colorless, odorless, nonmetallic, tasteless, highly flammable diatomic gas with the molecular formula H
2...
4NNitrogen is a chemical element that has the symbol N and atomic number 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78% by volume of Earth's atmosphere.Many industrially important...
2OOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
5, is a
cellularThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
metabolicMetabolism is the set of chemical reactions that occur in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter,...
poison. It
uncouplesAn uncoupling protein is a mitochondrial inner membrane protein that can dissipate the proton gradient before it can be used to provide the energy for oxidative phosphorylation.There are five types known in mammals:* UCP1, also known as thermogenin* UCP2...
oxidative phosphorylationOxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all carry out oxidative phosphorylation to produce ATP, the molecule that...
by carrying protons across the mitochondrial membrane, leading to a rapid consumption of
energyIn physics, energy is a scalar physical quantity that describes the amount of work that can be performed by a force, an attribute of objects and systems that is subject to a conservation law...
without generation of
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
.
Dinitrophenols as a class of compounds, of which there are six members, do not occur naturally but are all manufactured compounds.
2,4-Dinitrophenol is a yellow, crystalline solid that has a sweet, musty odor.
2,4-Dinitrophenol (
DNP),
CCarbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
6HHydrogen is the chemical element with atomic number 1. It is represented by the symbol H. At standard temperature and pressure, hydrogen is a colorless, odorless, nonmetallic, tasteless, highly flammable diatomic gas with the molecular formula H
2...
4NNitrogen is a chemical element that has the symbol N and atomic number 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78% by volume of Earth's atmosphere.Many industrially important...
2OOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
5, is a
cellularThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
metabolicMetabolism is the set of chemical reactions that occur in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter,...
poison. It
uncouplesAn uncoupling protein is a mitochondrial inner membrane protein that can dissipate the proton gradient before it can be used to provide the energy for oxidative phosphorylation.There are five types known in mammals:* UCP1, also known as thermogenin* UCP2...
oxidative phosphorylationOxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all carry out oxidative phosphorylation to produce ATP, the molecule that...
by carrying protons across the mitochondrial membrane, leading to a rapid consumption of
energyIn physics, energy is a scalar physical quantity that describes the amount of work that can be performed by a force, an attribute of objects and systems that is subject to a conservation law...
without generation of
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
.
Dinitrophenols as a class of compounds, of which there are six members, do not occur naturally but are all manufactured compounds.
Chemical properties
2,4-Dinitrophenol is a yellow, crystalline solid that has a sweet, musty odor. It sublimes when carefully heated and is volatile with steam. It is soluble in water (sparingly) (its crystalline sodium salts are also soluble in water), cold water (sparingly),
ethyl acetateEthyl acetate is the organic compound with the formula CH3COOCH2CH3. This colorless liquid has a characteristic sweet smell like certain glues or nail polish removers, in which it is used...
,
acetoneAcetone is the organic compound with the formula OC2. This colorless, mobile, flammable liquid is the simplest example of the ketones. Owing to the fact that acetone is miscible with water it serves as an important solvent in its own right, typically as the solvent of choice for...
,
chloroformChloroform is the organic compound with formula CHCl
3. This colourless, sweet-smelling, dense liquid is a trihalomethane. It is also considered somewhat hazardous...
,
pyridinePyridine is a simple aromatic heterocyclic organic compound with the chemical formula C
5H
5N used as a precursor to agrochemicals and pharmaceuticals, and is also an important solvent and reagent. It is structurally related to benzene, wherein one CH group in the aromatic...
,
carbon tetrachlorideCarbon tetrachloride, also known by many other names is the organic compound with the formula CCl
4. It is a reagent in synthetic chemistry and was formerly widely used in fire extinguishers, as a precursor to refrigerants, and as a cleaning agent...
,
tolueneToluene, also known as methylbenzene, or Toluol, is a clear water-insoluble liquid with the typical smell of paint thinners, reminiscent of the related compound benzene. It is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent...
,
alcoholEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug, best known as the type of alcohol found in alcoholic beverages and in modern thermometers. Ethanol is one of the oldest recreational drugs...
,
benzeneBenzene, or benzol, is an organic chemical compound with the molecular formula C6H6. It is sometimes abbreviated Ph–H. Benzene is a colorless and highly flammable liquid with a sweet smell and a relatively high melting point...
, and aqueous alkaline solutions (Merck, 1989). It forms explosive salts with alkalies and
ammoniaAmmonia is a compound of nitrogen and hydrogen with the formula NH
3. It is normally encountered as a gas with a characteristic pungent odor. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to foodstuffs and fertilizers...
, and emits toxic fumes of nitrogen oxides when heated to decomposition (Sax, 1989). It is incompatible with heavy metals and their compounds.
Uses
Commercial DNP is primarily used for scientific research and in manufacturing. It has been used at times to make
dyeA dye can generally be described as a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and may require a mordant to improve the fastness of the dye on the fiber....
s, other organic chemicals, and wood preservatives. It has also been used to make photographic developer, explosives, and pesticides.
Pharmacological action
In living cells, DNP acts as a proton
ionophoreAn ionophore is a lipid-soluble molecule usually synthesized by microorganisms to transport ions across the lipid bilayer of the cell membrane...
, an agent that can shuttle protons (hydrogen ions) across biological membranes. It defeats the proton gradient across mitochondria and
chloroplastChloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.The word chloroplast is...
membranes, collapsing the proton motive force that the cell uses to produce most of its
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
chemical energy. Instead of producing ATP, the energy of the proton gradient is lost as
heatIn physics and thermodynamics, heat is the process of energy transfer from one body or system due to thermal contact, which in turn is defined as an energy transfer to a body in any other way than due to work performed on the body....
.
DNP is often used in
biochemistryBiochemistry is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acids and other biomolecules....
researchResearch can be defined to be search for knowledge or any systematic investigation to establish facts. The primary purpose for applied research is discovering, interpreting, and the development of methods and systems for the advancement of human knowledge on a wide variety of scientific matters of...
to help explore the
bioenergeticsBioenergetics is the subject of a field of biochemistry that concerns energy flow through living systems. This is an active area of biological research that includes the study of thousands of different cellular processes such as cellular respiration and the many other metabolic processes that can...
of
chemiosmoticChemiosmosis is the diffusion of ions across a selectively-permeable membrane. More specifically, it relates to the generation of ATP by the movement of hydrogen ions across a membrane during cellular respiration....
and other membrane transport processes.
Dieting aid
DNP was used extensively in the 1930s in diet pills after Cutting and Tainter at Stanford University made their first report on the drug's ability to greatly increase metabolic rate. DNP acts as a protonophore in the mitochondrial membrane, uncoupling
oxidative phosphorylationOxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all carry out oxidative phosphorylation to produce ATP, the molecule that...
and making ATP energy production less efficient. In effect, part of the energy that is normally produced from cellular respiration is wasted as heat. This inefficiency is proportional to the dose of DNP that is taken. Thus, as the dose increases and energy production is made less efficient, the metabolic rate is increased (and more fat is burned) in order to compensate for the inefficiency and meet energy demands. Interestingly, the factor that limits ever increasing doses of DNP is not a lack of ATP energy production, but rather an excessive rise in body temperature due to the heat produced during uncoupling. Accordingly, DNP overdose will cause a fatal fever. Case reports have shown that an acute administration of 20–50 mg/kg in humans can be lethal. Concerns about dangerous side-effects and rapidly developing cataracts resulted in DNP being discontinued in the United States by the end of 1938. DNP, however, continues to be used by some
bodybuildersBodybuilding is a form of body modification involving intensive muscle hypertrophy; an individual who engages in this activity is referred to as a bodybuilder. In competitive bodybuilding, bodybuilders display their physiques to a panel of judges, who assign points based on their appearance...
and athletes to rapidly lose body fat. Fatal overdoses are rare, but are still reported on occasion. These include cases of accidental exposure, suicide, and excessive intentional exposure.
Some advocates of the drug advise people to take doses of 5–8 mg/kg daily. It's commonly advised, however, that the dose be slowly titrated according to personal tolerance, which varies greatly.
There is limited and conflicting data on the pharmacokinetics of DNP in humans. The EPA states that "Data on the elimination kinetics of the dinitrophenols or their metabolic products in humans were not found." The ATSDR's Toxicological Profile for Dinitrophenols also states that "No studies were located regarding distribution in humans after oral exposure to 2,4-DNP. Limited information is available regarding distribution in animals after oral exposure to 2,4-DNP." However, they do state that "Elimination from the body appears to be rapid, except possibly in cases of compromised liver function." This coincides with a review in the NEJM on the biological actions of dinitrophenol, which stated that "Judging from the metabolic response, DNP appears to be eliminated entirely in three or four days; in the presence of liver or kidney damage it is possible that the drug will be retained over a longer period." Oddly, more recent papers give an array of possible half-lives, ranging from 3 hours, to 5–14 days. Other recent papers maintain that the half-life in humans is unknown.
In a study on mice, a lethal dose of 35 mg/kg decreased to 5 mg/kg body weight when the environmental temperature was raised to 39°C (102.2°F). As the ambient temperature increases, so does the risk of overheating. People who use increased ambient temperatures for weight-loss, such as wrestlers and runners, are potentially at greater risk of overdose.
Although further investigation is needed, dinitrophenol-induced hyperthermia has been successfully resolved with
dantroleneDantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia...
administration. "Dinitrophenol uncouples oxidative phosphorylation, causes release of calcium from mitochondrial stores and prevents calcium re-uptake. This leads to free intracellular calcium and causes muscle contraction and hyperthermia. Dantrolene inhibits calcium release from the sarcoplasmic reticulum which reduces intracellular calcium. The resulting muscle relaxation allows heat dissipation. There is little risk to dantrolene administration. Since dantrolene may be effective in reducing hyperthermia caused by agents that inhibit oxidative phosphorylation, early administration may improve outcome."
While DNP itself is considered by many to be too risky for human use, its mechanism of action remains under investigation as a potential approach for treating obesity. Currently, research is being conducted on
uncoupling proteinAn uncoupling protein is a mitochondrial inner membrane protein that can dissipate the proton gradient before it can be used to provide the energy for oxidative phosphorylation.There are five types known in mammals:* UCP1, also known as thermogenin* UCP2...
s naturally found in humans.
Environmental toxicity
DNP is considered an important environmental contaminant by the
United States Environmental Protection AgencyThe U.S. Environmental Protection Agency is an agency of the federal government of the United States charged to regulate chemicals and protect human health by safeguarding the natural environment: air, water, and land...
. It has been found in 61 of 1400 priority sites that need clean-up of industrial waste. It can enter the air from automobile exhaust, burning of certain industrial substances, and from reaction of nitrogen in air with other atmospheric chemicals. The major site of degradation is the soil, where microorganisms metabolize it.
However the effects of DNP on
anaerobicAn anaerobic organism or anaerobe is any organism that does not require oxygen for growth and may even die in its presence. There are three types: obligate anaerobes, which cannot use oxygen for growth and are even harmed by it; aerotolerant organisms, which cannot use oxygen for growth, but...
micro-organisms are still largely undetermined. Some studies suggest there is anaerobic toxicity due to a reduced methane production.
External links