Tmic
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Record Information
Version2.0
Creation Date2009-03-06 18:58:12 UTC
Update Date2014-12-24 20:21:15 UTC
Accession NumberT3D0167
Identification
Common Name1,2-Diphenylhydrazine
ClassSmall Molecule
Description1,2-Diphenylhydrazine is a white solid. It dissolves only slightly in water and does not change into a gas unless it is heated to very high temperatures. It sticks to soil and can be carried into the air along with windblown dust. Once in water or exposed to air it is changed into other chemicals within minutes. These chemicals include the toxic chemicals azobenzene and benzidine. 1,2-Diphenylhydrazine is used to make fabric dyes in other countries, and to make certain medicines. (2)
Compound Type
  • Amine
  • Aromatic Hydrocarbon
  • Hydrazine
  • Industrial/Workplace Toxin
  • Lachrymator
  • Organic Compound
  • Organochloride
  • Pollutant
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1, 2-Diphenylhydrazine
1,1'-Hydrazodibenzene
1,2-Diphenyldrazine
Diphenylhydrazine
Hydrazobenzene
Hydrazodibenzene
N, N'-bianiline
N,N'-bianiline
N,N'-diphenylhydrazine
SYM-diphenylhydrazine
Symmetrical diphenyl hydrazine
Chemical FormulaC12H12N2
Average Molecular Mass184.237 g/mol
Monoisotopic Mass184.100 g/mol
CAS Registry Number122-66-7
IUPAC Name1,2-diphenylhydrazine
Traditional Namehydrazobenzene
SMILESN(NC1=CC=CC=C1)C1=CC=CC=C1
InChI IdentifierInChI=1S/C12H12N2/c1-3-7-11(8-4-1)13-14-12-9-5-2-6-10-12/h1-10,13-14H
InChI KeyInChIKey=YBQZXXMEJHZYMB-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as phenylhydrazines. These are compounds containing a phenylhydrazide moiety, which consists of a hydrazide substituent attached to a phenyl group.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassBenzene and substituted derivatives
Direct ParentPhenylhydrazines
Alternative Parents
Substituents
  • Phenylhydrazine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Hydrazine derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point131°C
Boiling PointNot Available
Solubility0.221 mg/mL at 25 °C [KUHNE,R et al. (1995)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.58 g/LALOGPS
logP2.88ALOGPS
logP3.76ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)19.22ChemAxon
pKa (Strongest Basic)1.29ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area24.06 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity60.96 m³·mol⁻¹ChemAxon
Polarizability20.92 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-1900000000-ff7fc7e452da47e1d4cdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-6900000000-585ccdbb89931863ff59View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014l-9100000000-292c3e31b59b6ed72bb1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2900000000-a30070f306c4a8c7b8ddView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-3900000000-a317f40733db3adc46fbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-d24c9ea196896869d171View in MoNA
MSMass Spectrum (Electron Ionization)splash10-00lu-9400000000-651a67b3ed4972e5e837View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityTwo of the known metabolites, aniline and benzidine, may contribute to the toxicity and/or carcinogenicity of 1,2-diphenylhydrazine. Nonneoplastic liver lesions, hepatocellular carcinomas and/or neoplastic liver nodules indicate that the liver is a target of 1,2-diphenylhydrazine toxicity. As aniline and other aromatic amino metabolites of 1,2-diphenylhydrazine (e.g., aminophenols) are methemoglobinforming compounds by either oral or inhalation routes of exposure, it is possible that 1,2-diphenylhydrazine may cause methemoglobinemia in humans. (2)
MetabolismUnchanged 1,2-diphenylhydrazine was detected following treatment by all routes, and aniline and benzidine were identified following oral and intraperitoneal treatments. Other metabolites included two unspecified hydroxy derivatives of benzidine (oral route), 2- and 4- aminophenol (intraperitoneal route), and unidentified compounds (oral, intravenous, and intratracheal routes). Aniline is oxidized by hydroxylation of a ring carbon to form 2-or 4-aminophenol or of the nitrogen to form phenylhydroxylamine, and then is conjugated to glucuronic or sulfuric acid. Benzidine is formed readily from 1,2-diphenylhydrazine by acid rearrangement. It has been suggested that benzidine may be produced from 1,2-diphenylhydrazine by acidity in the stomach. (2)
Toxicity ValuesLD50: 959 mg/kg (Oral, Rat) (2)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC. Benzidine, a metabolite of 1,2-diphenylhydrazine, is carcinogenic to humans (Group 1). Aniline, another metabolite, is not classifiable as to its carcinogenicity to humans (Group 3). (3)
Uses/Sources1,2-Diphenylhydrazine is used to make fabric dyes in other countries, and to make certain medicines. Exposure may result from breathing in dust coated with 1,2-diphenylhydrazine and eating dirt or smearing contaminated dirt on the skin. (2)
Minimum Risk LevelNot Available
Health EffectsNonneoplastic liver lesions, hepatocellular carcinomas and/or neoplastic liver nodules; seizures and coma. (2)
SymptomsIrritatinon to the eyes, nose and respiratory system, depending on the route of exposure. Cough, redness of the exposed surface. (2)
TreatmentConsider gastric lavage after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion. Following inhalation, move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If the exposure occurs through dermal contact remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. (1)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID31222
ChEMBL IDCHEMBL558459
ChemSpider ID28962
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc ID4-HYDROXYMETHYLPHENYLHYDRAZINE
CTD IDC032041
Stitch ID1,2-Diphenylhydrazine
PDB IDNot Available
ACToR ID721
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0167.pdf
General References
  1. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  2. ATSDR - Agency for Toxic Substances and Disease Registry (1990). Toxicological profile for 1,2-diphenylhydrazine. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  3. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]