Juglone, also called 5-hydroxy-1,4-naphthalenedione (

IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...

) is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

with the

molecular formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...

C₁₀H₆O₃. In the food industry, juglone is also known as C.I. Natural Brown 7 and C.I. 75500. It is insoluble in benzene but soluble in dioxane, from which it crystallizes as yellow needles. It is an

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...

of lawsone, which is the staining compound in the

henna Henna is a dye prepared from the plant ''Lawsonia inermis'', also known as the henna tree, the mignonette tree, and the Egyptian privet, the sole species of the genus ''Lawsonia''. ''Henna'' can also refer to the temporary body art resulting fr ...

leaf. Juglone occurs naturally in the leaves, roots, husks, fruit ( the epicarp), and bark of plants in the

Juglandaceae The Juglandaceae are a plant family known as the walnut family. They are trees, or sometimes shrubs, in the order Fagales. Members of this family are native to the Americas, Eurasia, and Southeast Asia. The nine or ten genera in the family have ...

family, particularly the

black walnut ''Juglans nigra'', the eastern American black walnut, is a species of deciduous tree in the walnut family, Juglandaceae, native to North America. It grows mostly in riparian zones, from southern Ontario, west to southeast South Dakota, south to ...

(''Juglans nigra''), and is toxic or growth-stunting to many types of plants. It is sometimes used as an

herbicide Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page f ...

, as a

dye A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution and ...

for cloth and inks, and as a coloring agent for foods and

cosmetics Cosmetics are constituted mixtures of chemical compounds derived from either natural sources, or synthetically created ones. Cosmetics have various purposes. Those designed for personal care and skin care can be used to cleanse or protec ...

History

The harmful effects of

walnut A walnut is the edible seed of a drupe of any tree of the genus ''Juglans'' (family Juglandaceae), particularly the Persian or English walnut, '' Juglans regia''. Although culinarily considered a "nut" and used as such, it is not a true ...

trees on other plants have been observed for at least two millennia. The ancient civilizations of Greece and Rome used the walnut for its

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating c ...

properties as did residents of the American South for easily gathering fish when they threw cut husks into the water with the fish. However, juglone was not isolated until the 1850s. Two men, A. Vogel Jr. and C. Reischauer, were able to isolate the compound from the walnut tree in 1851. The compound was known as nucin at that time. Juglone was then synthesized and characterized for the first time in 1887 by A. Bernthsen and A. Semper. While at the Virginia Agricultural Experiment Station in 1921, M.T. Cook found that tomato plants in the vicinity of ''Juglans nigra'' were negatively affected, most notably by their wilted leaves. Schneiderhan found that ''Juglans nigra'' and ''Juglans cinerea'' were damaging apple trees in Virginia. The trees that were within an average of 11.9 meters from the walnut trees were found dead. All damaged trees in their vicinity average about 14.3 meters away. In addition, he found that certain local variations of the apple trees tended to be more resistant to the walnuts. A.B. Massey observed that the walnut trees in alfalfa fields caused the alfalfa to die away in place of grass. After several other experiments, Massey concluded that the toxic compound found in walnut trees was not easily soluble in water, so the compound in the roots and bark must change chemically after it leaves the tree. It was not until 1928 the compound was identified and confirmed to be

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a sub ...

to other plants by E.F. Davis. After the scientific news of the harm walnut trees caused certain crops and trees, there was backlash from the scientific community to refute these findings. On one account, A.G. Miller claimed that the trees that Schneiderhan observed to be harming the apple trees in Virginia were not in fact walnut trees. By 1942, B.I. Brown showed that tomato and alfalfa germination and seedling growth was slowed down by being in contact with pieces of walnut roots, adding further scientific evidence to the biological damage of juglone. The walnut tree has historically been used within the field of

traditional medicine Traditional medicine (also known as indigenous medicine or folk medicine) comprises medical aspects of traditional knowledge that developed over generations within the folk beliefs of various societies, including indigenous peoples, before the ...

. In America during the early 1900s, doctors prescribed juglone for the treatment of various skin diseases.

Chemistry

Synthesis

Juglone is derived by oxidation of hydrojuglone, 1,5-dihydroxynaphthalene, after enzymatic hydrolysis.Gerald Booth "Naphthalene Derivatives" in ''Ullmann's Encyclopedia of Industrial Chemistry'', 2005, Wiley-VCH, Weinheim. . It can also be obtained by oxidations of 5,8-dihydroxy-1-tetralone with silver oxide (Ag₂O),

manganese dioxide Manganese dioxide is the inorganic compound with the formula . This blackish or brown solid occurs naturally as the mineral pyrolusite, which is the main ore of manganese and a component of manganese nodules. The principal use for is for dry-ce ...

(MnO₂), or

2,3-dichloro-5,6-dicyano-1,4-benzoquinone 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (or DDQ) is the chemical reagent with formula C6Cl2(CN)2O2. This oxidant is useful for the dehydrogenation of alcohols, phenols, and steroid ketones. DDQ decomposes in water, but is stable in aqueous mine ...

(DDQ).

Extraction

Juglone has been extracted from the husk of

fruit of which it contains 2-4% by fresh weight.

Degradation

Before oxidization, juglone exists in plants such as walnuts in the form of colorless hydroxyjuglone, with both O groups replaced with OH groups. This is rapidly oxidized to juglone once exposed to air. The evidence that hydroxyjuglone is readily degraded is most apparent in the color change of walnut hulls from yellow to black after being freshly cut. Indigenous bacteria found in the soil of black walnut roots, most notably '' Pseudomonas putida'' J1, are able to metabolize juglone and use it as their primary source of energy and carbon. Because of this, juglone is not so active as a cytotoxin in well-aerated soils.

Biological effects

Juglone is an

allelopathic Allelopathy is a biological phenomenon by which an organism produces one or more biochemicals that influence the germination, growth, survival, and reproduction of other organisms. These biochemicals are known as allelochemicals and can have ben ...

compound, a substance produced by a plant to stunt the growth of another plant. Juglone affects

germination Germination is the process by which an organism grows from a seed or spore. The term is applied to the sprouting of a seedling from a seed of an angiosperm or gymnosperm, the growth of a sporeling from a spore, such as the spores of fungi, fe ...

of plants less than it affects growth of the root and stem systems. In below average concentrations, it has increased the rate of germination in some

coniferous Conifers are a group of cone-bearing seed plants, a subset of gymnosperms. Scientifically, they make up the division Pinophyta (), also known as Coniferophyta () or Coniferae. The division contains a single extant class, Pinopsida. All ext ...

seeds. Juglone exerts its effect by inhibiting certain

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s needed for metabolic function. This in turn inhibits the effects of respiration of mitochondria and inhibits photosynthesis found in common crops such as

maize Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maíz after tnq, mahiz), also known as corn (North American English, North American and Australian English), is a cereal grain first domesticated by indigenous peoples of Mexico, indigenous ...

and soy at juglone concentrations that are at or below those common in nature. In addition to these inhibitions, juglone has been shown to alter the relationship between plants and water because of its effect on

stoma In botany, a stoma (from Greek ''στόμα'', "mouth", plural "stomata"), also called a stomate (plural "stomates"), is a pore found in the epidermis of leaves, stems, and other organs, that controls the rate of gas exchange. The pore is bo ...

tal functioning. The rise in popularity of

alley cropping Agroforestry is a land use management system in which trees or shrubs are grown around or among crops or pastureland. Trees produce a wide range of useful and marketable products from fruits/nuts, medicines, wood products, etc. This intentional ...

with black walnut trees and maize in the

American Midwest The Midwestern United States, also referred to as the Midwest or the American Midwest, is one of four census regions of the United States Census Bureau (also known as "Region 2"). It occupies the northern central part of the United States. I ...

, due to the high value of black walnut trees, has led to certain studies being conducted about the particular relationship between the two species. Research has shown that juglone affects the yield of maize crops; however, the practice of

pruning Pruning is a horticultural, arboricultural, and silvicultural practice involving the selective removal of certain parts of a plant, such as branches, buds, or roots. The practice entails the ''targeted'' removal of diseased, damaged, dead, ...

and usage of

root barrier A root barrier is an underground wall placed to block plant roots. This is often for the purpose of protecting structures or other plants, but root barriers are also used to preserve soil moisture. Development Root barriers were developed to sto ...

s greatly reduce these effects. Some plants and trees are resistant to juglone including some species of

maple ''Acer'' () is a genus of trees and shrubs commonly known as maples. The genus is placed in the family Sapindaceae.Stevens, P. F. (2001 onwards). Angiosperm Phylogeny Website. Version 9, June 2008 nd more or less continuously updated since h ...

(''Acer''),

birch A birch is a thin-leaved deciduous hardwood tree of the genus ''Betula'' (), in the family Betulaceae, which also includes alders, hazels, and hornbeams. It is closely related to the beech- oak family Fagaceae. The genus ''Betula'' cont ...

(''Betula''), and

beech Beech (''Fagus'') is a genus of deciduous trees in the family Fagaceae, native to temperate Europe, Asia, and North America. Recent classifications recognize 10 to 13 species in two distinct subgenera, ''Engleriana'' and ''Fagus''. The ''Engl ...

(''Fagus''). It is highly toxic to many insect herbivores. However, some of them, example ''

Actias luna The Luna moth (''Actias luna'') also known as the American moon moth is a Nearctic moth in the family Saturniidae, subfamily Saturniinae, a group commonly known as giant silk moths. It has lime-green colored wings and a white body. The larvae ( ...

'' (Luna moth), can detoxify juglone (and related naphthoquinones) to non-toxic 1,4,5-trihydroxy

naphthalene Naphthalene is an organic compound with formula . It is the simplest polycyclic aromatic hydrocarbon, and is a white crystalline solid with a characteristic odor that is detectable at concentrations as low as 0.08 ppm by mass. As an aromat ...

. It has also shown

anthelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may ...

(expelling parasitic worms) activity on mature and immature '' Hymenolepis nana'' in mice. Napthoquinonic compounds also exhibit antimicrobial activity. Juglone has been studied for its anticancer properties. It has been shown to decrease the probability of intestinal tumors in rats that have been exposed to carcinogens. One of the potential pathways through which juglone achieves its anticancer properties is through the formation of the

semiquinone Semiquinone (or ubisemiquinone) is a free radical resulting from the removal of one hydrogen atom with its electron during the process of dehydrogenation of a hydroquinone, such as hydroquinone itself or catechol, to a quinone or alternatively the ...

radical; the semiquinone radical causes

superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...

anion radicals to form which can lead to

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...

when present in large concentrations. This conversion from juglone to semiquinone radical that causes the superoxide anion radical to form takes place in the mitochondria as well as the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

Uses

Juglone is occasionally used as a

. Traditionally, juglone has been used as a natural dye for clothing and fabrics, particularly

wool Wool is the textile fibre obtained from sheep and other mammals, especially goats, rabbits, and camelids. The term may also refer to inorganic materials, such as mineral wool and glass wool, that have properties similar to animal wool. ...

, and as ink. Because of its tendency to create dark orange-brown stains, juglone has also found use as a coloring agent for foods and cosmetics, such as hair dyes.

Spectral data

The spectral data for juglone are consistent with the structure. The IR spectrum for juglone shows peaks at 3400, 1662, and 1641 cm⁻¹ which are characteristic respectively of the hydroxyl and two carbonyl groups. The ¹³C NMR spectrum shows 10 peaks, including signals at 160.6, 183.2, and 189.3 ppm for the hydroxyl and two carbonyl carbons.