In biochemistry, naturally occurring phenols are containing at least one phenol functional group.
Classification
Various classification schemes can be applied.
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| 6 | C6 | 1 | Simple phenols, | Catechol, Hydroquinone, 2,6-Dimethoxybenzoquinone |
| 7 | C6-C1 | 1 | , Phenolic aldehydes | Gallic, salicylic acids |
| 8 | C6-C2 | 1 | , Tyrosine derivatives, Phenylacetic acids | 3-Acetyl-6-methoxybenzaldehyde, Tyrosol, p-Hydroxyphenylacetic acid, Homogentisic acid |
| 9 | C6-C3 | 1 | Hydroxycinnamic acids, , , , | Caffeic, ferulic acids, Myristicin, Eugenol, Umbelliferone, aesculetin, Bergenon, Eugenin |
| 10 | C6-C4 | 1 | | Juglone, Plumbagin |
| 13 | C6-C1-C6 | 2 | | Mangiferin |
| 14 | C6-C2-C6 | 2 | , Anthraquinones | Resveratrol, Emodin |
| 15 | C6-C3-C6 | 2 | , , Isoflavonoids, Neoflavonoids | Quercetin, cyanidin, Genistein |
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| 16 | C6-C4-C6 | 2 | Halogenated algal phenolic compounds | Kaviol A, colpol |
| 18 | (C6-C3)2 | 2 | , | Pinoresinol, Eusiderin |
| 30 | (C6-C3-C6)2 | 4 | | Amentoflavone |
| many | (C6-C3)n,
(C6)n,
(C6-C3-C6)n | n > 12 | ,
,
Flavolans (),
Polyphenolic proteins,
| Raspberry ellagitannin,
Tannic acid |
C6-C7-C6 are not included in this Harborne classification.
They can also be classified on the basis of their number of phenol groups. They can therefore be called simple phenols or monophenols, with only one phenolic group, or di- ( bi-), tri- and oligophenols, with two, three or several phenolic groups respectively.
A diverse family natural phenols are the , which include several thousand compounds, among them the , , flavan-3ol ( catechins), , , and .
The phenolic unit can be found dimerized or further polymerized, creating a new class of polyphenol. For example, ellagic acid is a dimer of gallic acid and forms the class of ellagitannins, or a catechin and a gallocatechin can combine to form the red compound theaflavin, a process that also results in the large class of brown in tea.
Two natural phenols from two different categories, for instance a flavonoid and a lignan, can combine to form a hybrid class like the .
Nomenclature of :
Hybrid chemical classes
Plants in the genus Humulus and Cannabis produce terpenophenolic metabolites, compounds that are .[Chapter eight: "Biosynthesis of terpenophenolic metabolites in hop and cannabis". Jonathan E. Page and Jana Nagel, Recent Advances in Phytochemistry, 2006, Volume 40, pp. 179–210, ]
Chirality
Many natural phenols are chiral. An example of such molecules is catechin. Cavicularin is an unusual macrocycle because it was the first compound isolated from nature displaying optical activity due to the presence of planar chirality and axial chirality.
UV visible absorbance
Natural phenols show optical properties characteristic of benzene, e.g. absorption near 270 nm. According to Woodward's rules, bathochromic shifts often also happen suggesting the presence of delocalised π electrons arising from a conjugation between the benzene and Vinyl group groups.
As molecules with higher conjugation levels undergo this bathochromic shift phenomenon, a part of the visible spectrum is absorbed. The wavelengths left in the process (generally in red section of the spectrum) recompose the color of the particular substance. Acylation with cinnamic acids of shifted color tonality (CIE Lab hue angle) to purple.
Here is a series of UV visible spectrum spectra of molecules classified from left to right according to their conjugation level:
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| , with lambda max around 270 nanometers (nm)]] | , with lambda max at 321 and a shoulder at 278 nm.]] | , with lambda max at 369 nm.]] | (chrysanthemin), with lambda max at 518 nm.]] |
| , a phenolic acid]] | , a hydroxycinnamic acid]] | , a flavonol]] | , an anthocyanidin]] |
The absorbance pattern responsible for the red color of may be complementary to that of green chlorophyll in photosynthetically active tissues such as young Quercus coccifera leaves.
Oxidation
Natural phenols are reactive species toward oxidation, notably the complex mixture of phenolics, found in food for example, can undergo autoxidation during the ageing process. Simple natural phenols can lead to the formation of B type proanthocyanidins in wines
Browning associated with oxidation of phenolic compounds has also been given as the cause of cells death in calli formed in in vitro cultures. Those phenolics originate both from explant tissues and from explant secretions.
Phenolic compounds
Naturally occurring
Biosynthesis
Phenolics are formed by three different biosynthetic pathways: (i) the shikimate/chorizmate or succinylbenzoate pathway, which produces the phenyl propanoid derivatives (C6–C3); (ii) the acetate/malonate or polyketide pathway, which produces the side-chain-elongated phenyl propanoids, including the large group of flavonoids (C6–C3–C6) and some quinones; and (iii) the acetate/mevalonate pathway, which produces the aromatic terpenoids, mostly monoterpenes, by dehydrogenation reactions.
In plants, the phenolic units are or methylation and are submitted to conjugation, which means that the natural phenols are mostly found in the glycoside form instead of the aglycone form.
In olive oil, tyrosol forms esters with fatty acids.
Some acetylations involve like geraniol.
Methylations can occur by the formation of an ether bond on hydroxyl groups forming O-methylated polyphenols. In the case of the O-methylated flavone tangeritin, all of the five hydroxyls are methylated, leaving no free hydroxyls of the phenol group. Methylations can also occur on directly on a carbon of the benzene ring like in the case of poriol, a C-methylated flavonoid.
Biodegradation
The white rot fungus Phanerochaete chrysosporium can remove up to 80% of phenolic compounds from coking waste water.
Applications
are used in the tanning industry.
Aspirational uses
Some natural phenols have been proposed as . like karanjin or are used as acaricide or insecticide.
Some phenols are sold as dietary supplements. Phenols have been investigated as drugs. For instance, Crofelemer (USAN trade name Fulyzaq) is a drug under development for the treatment of diarrhea associated with anti-HIV drugs. Additionally, derivatives have been made of phenolic compound, combretastatin A-4, an anticancer molecule, including nitrogen or halogens atoms to increase the efficacy of the treatment.
Industrial processing and analysis
Biomass
The recovery of natural phenols from biomass residue is part of biorefinery.
Analytical methods
Studies on evaluating antioxidant capacity can use electrochemical methods.
Detection can be made by recombinant luminescent bacterial .
Profiling
Phenolic profiling can be achieved with liquid chromatography–mass spectrometry (LC/MS).
Quantification
A method for phenolic content quantification is volumetric titration. An oxidizing agent, permanganate, is used to oxidize known concentrations of a standard solution, producing a standard curve. The content of the unknown phenols is then expressed as equivalents of the appropriate standard.
Some methods for quantification of total phenolic content are based on colorimetry measurements. Total phenols (or antioxidant effect) can be measured using the Folin-Ciocalteu reaction. Results are typically expressed as gallic acid equivalents (GAE). Ferric chloride (FeCl3) test is also a colorimetric assay.
Lamaison and Carnet have designed a test for the determination of the total flavonoid content of a sample (AlCI3 method). After proper mixing of the sample and the reagent, the mixture is incubated for 10 minutes at ambient temperature and the absorbance of the solution is read at 440 nm. Flavonoid content is expressed in mg/g of quercetin.["Teneurs en principaux flavonoides des fleurs de Cratageus monogyna Jacq et de Cratageus Laevigata (Poiret D.C.) en Fonction de la vegetation". J. L. Lamaison and A. Carnet, Plantes Medicinales Phytotherapie, 1991, XXV, pages 12–16]
Quantitation results produced by the means of diode array detector-coupled HPLC are generally given as relative rather than as there is a lack of commercially available standards for every phenolic molecules. The technique can also be coupled with mass spectrometry (for example, HPLC–DAD–ESI/MS) for more precise molecule identification.
Antioxidant effect assessment
- In vitro measurements
Other tests measure the antioxidant capacity of a fraction. Some make use of the ABTS (ABTS) radical cation, which is reactive towards most antioxidants including phenolics, and vitamin C.
Other antioxidant capacity assays that use Trolox as a standard include the diphenylpicrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC), ferric reducing ability of plasma (FRAP) assays or inhibition of copper-catalyzed in vitro human low-density lipoprotein oxidation.
A cellular antioxidant activity (CAA) assay also exists. Dichlorofluorescin is a probe that is trapped within cells and is easily oxidized to fluorescent dichlorofluorescein (DCF). The method measures the ability of compounds to prevent the formation of DCF by 2,2'-Azobis(2-amidinopropane) dihydrochloride (ABAP)-generated peroxyl radicals in human hepatocarcinoma HepG2 cells.
Other methods include butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), Rancimat method (rancidification assessment of fat).
- In vivo models
Larvae of the model animal Galleria mellonella, also called , can be used to test the antioxidant effect of individual molecules using boric acid in food to induce an oxidative stress.
Genetic analysis
The phenolic biosynthetic and metabolic pathways and enzymes can be studied by means of transgenesis of genes. The Arabidopsis regulatory gene for production of Anthocyanin Pigment 1 (AtPAP1) can be expressed in other plant species.
Natural occurrences
Phenols are found in the natural world, especially in the plant kingdom.
Occurrences in prokaryotes
Orobol can be found in Streptomyces neyagawaensis (an Actinobacterium). Phenolic compounds can be found in the cyanobacterium Arthrospira maxima, used in the dietary supplement, Spirulina.[ Production of phenolic compounds by Spirulina maxima microalgae and their protective effects in vitro toward hepatotoxicity model. Abd El-Baky Hanaa H., El Baz Farouk K. and El-Baroty Gamal S., Advances in food sciences, 2009, volume 31, number 1, pp. 8–16, ] The three cyanobacteria Microcystis aeruginosa, Cylindrospermopsis raciborskii and Oscillatoria sp. are the subject of research into the natural production of butylated hydroxytoluene (BHT),
The proteobacterium Pseudomonas fluorescens produces phloroglucinol, phloroglucinol carboxylic acid and diacetylphloroglucinol.
Occurrences in fungi
can be found in mushroom basidiomycetes species.
- In yeasts
Aromatic alcohols (example: tyrosol) are produced by the yeast Candida albicans.
- Metabolism
Aryl-alcohol dehydrogenase uses an aromatic alcohol and NAD+ to produce an aromatic aldehyde, NADH and H+.
Aryl-alcohol dehydrogenase (NADP+) uses an aromatic alcohol and NADP+ to produce an aromatic aldehyde, NADPH and H+.
Aryldialkylphosphatase (also known as organophosphorus hydrolase, phosphotriesterase, and paraoxon hydrolase) uses an aryl dialkyl phosphate and H2O to produce dialkyl phosphate and an aryl alcohol.
Occurrences in lichen
Gyrophoric acid, a depside, and orcinol are found in lichen.
Occurrence in algae
The green alga Botryococcus braunii is the subject of research into the natural production of butylated hydroxytoluene (BHT),
Phenolic acids such as protocatechuic, p-hydroxybenzoic, 2,3-dihydroxybenzoic, chlorogenic acid, vanillic acid, caffeic acid, P-Coumaric acid and salicylic acid, cinnamic acid and hydroxybenzaldehydes such as p-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, vanillin have been isolated from in vitro culture of the freshwater green alga Spongiochloris spongiosa.
, for instance eckol, are found in brown algae. Vidalenolone can be found in the tropical red alga Vidalia sp.
Occurrence in land plants (embryophytes)
Occurrences in vascular plants
Phenolic compounds are mostly found in (tracheophytes) i.e. Lycopodiophyta
In ferns, compounds such as kaempferol and its glucoside can be isolated from the extract of fronds of Phegopteris connectilis[Flavonoids and a proanthrocyanidin from rhizomes of Selliguea feei. Baek Nam-In, Kennelly E. J., Kardono L. B. S., Tsauri S., Padmawinata K., Soejarto D. D. and Kinghorn A. D., Phytochemistry, 1994, vol. 36, no. 2, pp. 513–518, ] Hypogallic acid, caffeic acid, paeoniflorin and pikuroside can be isolated from the freshwater fern Salvinia molesta.
In conifers (Pinophyta), phenolics are stored in polyphenolic parenchyma cells, a tissue abundant in the phloem of all conifers.
The aquatic plant Myriophyllum spicatum produces ellagic acid, gallic acid and and (+)-catechin.
Occurrences in monocotyledons
can be found in cereals.
2,4-Bis(4-hydroxybenzyl)phenol is a phenolic compound found in the orchids Gastrodia elata and Galeola faberi.
Occurrences in non-vascular plants
Phenolics can also be found in non-vascular land plants (). Dihydrostilbenoids and bis(dibenzyls) can be found in liverworts (Marchantiophyta), for instance, the macrocycles cavicularin and riccardin C. Though lignin is absent in (Bryophyta) and (Anthocerotophyta), some phenolics can be found in those two taxa.
Occurrences in other eukaryotes
Occurrences in insects
The hardening of the protein component of insect cuticle has been shown to be due to the tanning action of an agent produced by oxidation of a phenolic substance forming sclerotin. In the analogous hardening of the cockroach ootheca, the phenolic substance concerned is 3:4-dihydroxybenzoic acid (protocatechuic acid).
Acetosyringone is produced by the male leaffooted bug ( Leptoglossus phyllopus) and used in its communication system.[ Acetosyringone on www.pherobase.com, the pheromones data base][ Semiochemical - 2-methoxy-4-vinylphenol, Pherobase.com] Other simple and complex phenols can be found in eusocial ants (such as Crematogaster) as components of venom.
Occurrences in mammals
In female elephants, the two compounds 3-ethyl phenol and 2-ethyl 4,5 dimethylphenol have been detected in urine samples.[Urinary, temporal gland, and breath odors from Asian elephants of Mudumalai National Park. L. E. L. Rasmussen and V. Krishnamurthy, Gajah, the Journal of the Asian Elephant Specialist Group, January 2001, Number 20, pages 1-8 ( article)] Temporal glands secretion examination showed the presence of phenol, m-cresol and p-cresol (4-methyl phenol) during musth in male .["Musth in elephants". Deepa Ananth, Zoo's print journal, 15(5), pp. 259-262 ( article )]
p-Cresol and o-cresol are also components of the human sweat. P-cresol is also a major component in pig odor.
4-Ethylphenol, 1,2-dihydroxybenzene, 3-hydroxyacetophenone, 4-methyl-1,2-dihydroxybenzene, 4-methoxyacetophenone, 5-methoxysalicylic acid, salicylaldehyde, and 3-hydroxybenzoic acid are components of castoreum, the exudate from the castor sacs of the mature North American beaver ( Castor canadensis) and the European beaver ( Castor fiber), used in perfumery.
Roles
In some cases of natural phenols, they are present in vegetative foliage to discourage herbivory, such as in the case of Western poison oak.[C.Michael Hogan (2008) Western poison-oak: Toxicodendron diversilobum, GlobalTwitcher, ed. Nicklas Stromberg ]
Role in soils
In , it is assumed that larger amounts of phenols are released from decomposing plant litter rather than from throughfall in any natural plant community. Decomposition of dead plant material causes complex organic compounds to be slowly oxidized lignin-like humus or to break down into simpler forms (sugars and amino sugars, aliphatic and phenolic organic acids), which are further transformed into microbial biomass (microbial humus) or are reorganized, and further oxidized, into humic assemblages (fulvic acid and humic acid acids), which bind to and . There has been a long debate about the ability of plants to uptake humic substances from their root systems and to metabolize them. There is now a consensus about how humus plays a hormonal role rather than simply a nutritional role in plant physiology.
In the soil, soluble phenols face four different fates. They might be degraded and mineralized as a carbon source by heterotrophic microorganisms; they can be transformed into insoluble and recalcitrant humic acid substances by polymerization and condensation reactions (with the contribution of soil organisms); they might adsorb to or form with aluminium or iron ions; or they might remain in dissolved form, leached by percolating water, and finally leave the ecosystem as part of dissolved organic carbon (DOC).[
]
Leaching is the process by which cations such as iron (Fe) and aluminum (Al), as well as organic matter, are removed from the litterfall and transported downward into the soil below. This process is known as podzolization and is particularly intense in boreal and cool temperate forests that are mainly constituted by coniferous pines, whose litterfall is rich in phenolic compounds and fulvic acid.[ Biogeochemistry: An Analysis of Global Change. 2nd Edition. William H. Schlesinger, Academic Press, 1997, 108, 135, 152–158, 180–183, 191–194]
Role in survival
Phenolic compounds can act as protective agents, inhibitors, natural animal toxicants and pesticides against invading organisms, i.e. herbivores, nematodes, phytophagous insects, and fungal and bacterial pathogens. The scent and pigmentation conferred by other phenolics can attract symbiotic microbes, pollinators and animals that disperse fruits.
Defense against predators
Volatile phenolic compounds are found in plant resin where they may attract benefactors such as or of the herbivores that attack the plant.[ Plant Resins: Chemistry, evolution, ecology, and ethnobotany, by Jean Langenheim, Timber Press, Portland, Oregon. 2003]
In the kelp species Alaria marginata, phenolics act as chemical defence against herbivores.
Defense against infection
In Vitis vinifera grape, trans-resveratrol is a phytoalexin produced against the growth of fungal pathogens such as Botrytis cinerea
Sakuranetin is a flavanone, a type of flavonoid. It can be found in Polymnia fruticosa[Sakuranetin, a flavonone phytoalexin from ultraviolet-irradiated rice leaves, Kodama O., Miyakawa J., Akatsuka T. and Kiyosawa S., Phytochemistry, 1992, volume 31, number 11, pp. 3807–3809, ] In Sorghum, the SbF3'H2 gene, encoding a flavonoid 3'-hydroxylase, seems to be expressed in Plant pathology-specific 3-deoxyanthocyanidin synthesis,["Biosynthesis and regulation of 3-deoxyanthocyanidin phytoalexins induced during Sorghum- Colletotrichum interaction: Heterologous expression in maize". Chopra Surinder, Gaffoor Iffa, Ibraheem Farag, Poster at the American Society of Plant Biologists ( abstract )]
6-Methoxymellein is a dihydroisocoumarin and a phytoalexin induced in carrot slices by Ultraviolet C,
Danielone is a phytoalexin found in the papaya fruit. This compound showed high antifungal activity against Colletotrichum gloesporioides, a pathogenic fungus of papaya.[ Danielone, a phytoalexin from papaya fruit. Echeverri F., Torres F., Quinones W., Cardona G., Archbold R., Roldan J., Brito I., Luis J. G., and Lahlou U. E.-H., Phytochemistry, 1997, vol. 44, no. 2, pp. 255–256, ]
Stilbenes are produced in Eucalyptus sideroxylon in case of pathogens attacks. Such compounds can be implied in the hypersensitive response of plants. High levels of phenolics in some woods can explain their natural preservation against rot.
In plants, VirA is a protein histidine kinase which senses certain sugars and phenolic compounds. These compounds are typically found from wounded plants, and as a result VirA is used by Agrobacterium tumefaciens to locate potential host organisms for infection.
Role in allelopathic interactions
Natural phenols can be involved in allelopathy interactions, for example in soil[
]
Phenolics, and in particular and , may be involved in formation.
Acetosyringone has been best known for its involvement in plant-pathogen recognition,["Involvement of acetosyringone in plant-pathogen recognition". Baker C. Jacyn, Mock Norton M., Whitaker Bruce D., Roberts Daniel P., Rice Clifford P., Deahl Kenneth L. and Aver'Yanov Andrey A., Biochemical and Biophysical Research Communications, 2005, volume 328, number 1, pp. 130–136, ] especially its role as a signal attracting and transforming unique, oncogenic bacteria in genus Agrobacterium. The virA gene on the Ti plasmid in the genome of Agrobacterium tumefaciens and Agrobacterium rhizogenes is used by these soil bacteria to infect plants, via its encoding for a receptor for acetosyringone and other phenolic phytochemicals exuded by plant wounds.
Content in human food
Notable sources of natural phenols in human nutrition include berry, tea, beer, olive oil, chocolate or Cocoa solids, coffee, , popcorn, yerba maté, and fruit based drinks (including cider, wine and vinegar) and . and , nuts (walnuts, peanut) and are also potentially significant for supplying certain natural phenols.
Natural phenols can also be found in fatty matrices like olive oil.
Phenolic compounds, when used in , such as prune juice, have been shown to be helpful in the color and sensory components, such as alleviating bitterness.
Some advocates for organic farming claim that organically grown , oranges, and have more phenolic compounds and these may provide antioxidant protection against heart disease and cancer.[Asami, Danny K. "Comparison of the Total Phenolic and Ascorbic Acid Content of Freeze-Dried and Air-Dried Marionberry, Strawberry, and Corn Grown Using Conventional, Organic, and Sustainable Agricultural Practices". Journal of Agricultural and Food Chemistry (American Chemical Society), 51 (5), 1237–1241, 2003. 10.1021/jf020635c S0021-8561(02)00635-0. Retrieved 10-Apr-2006.] However, evidence on substantial differences between organic food and conventional food is insufficient to support claims that organic food is safer or healthier than conventional food.[Blair, Robert. (2012). Organic Production and Food Quality: A Down to Earth Analysis. Wiley-Blackwell, Oxford, UK. ]
Human metabolism
In animals and humans, after ingestion, natural phenols become part of the xenobiotic metabolism. In subsequent phase II reactions, these activated metabolites are conjugated with charged species such as glutathione, sulfate, glycine or glucuronic acid. These reactions are catalysed by a large group of broad-specificity transferases. UGT1A6 is a human gene encoding a phenol UDP glucuronosyltransferase active on simple phenols.["Cloning and substrate specificity of a human phenol UDP glucuronosyltransferase expressed in COS-7 cells". David Harding, Sylvie Fournel-Gigleux, Michael R. Jackson and Brian Burchell, Proc. Natl. Acad. Sci. USA, November 1988, Volume 85, pp. 8381–8385, ( abstract)] The enzyme encoded by the gene UGT1A8 has glucuronidase activity with many substrates including , anthraquinones and .
Books
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Biochemistry of phenolic compounds, by J. B. Harborne, 1964, Academic Press ( Google Books)
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Plant phenolics, by Pascal Ribéreau-Gayon, 1972, Oliver and Boyd Editions ( Google Books, , )
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The Biochemistry of plant phenolics, by C. F. van Sumere and P. J. Lea, Phytochemical Society of Europe, 1985, Clarendon Press ( Google Books, )
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Biochemistry of Phenolic Compounds, by Wilfred Vermerris and Ralph Nicholson, 2006, Springer ( Google book)
External links
Databases
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Phenol-Explorer ( phenol-explorer.eu), a database dedicated to phenolics found in food by Augustin Scalbert, INRA Clermont-Ferrand, Unité de Nutrition Humaine (Human food unit)
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Phenols at ChEBI (Chemical Entities of Biological Interest)
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target="_blank" rel="nofollow"> ChEMBLdb, a database of bioactive drug-like small molecules by the European Bioinformatics Institute
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Foodb, a database of compounds found in food
