| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Electron donor for reversed oxidative phosphorylation
Menadiol targets the vitamin K-dependent carboxylation system and the mitochondrial electron transport chain. As a menaquinol analogue, menadiol serves as an electron donor for reversed oxidative phosphorylation in submitochondrial particles. It is converted in the liver to menaquinone-4 (MK-4), the biologically active form of vitamin K. MK-4 acts as a cofactor for γ-glutamyl carboxylase, an enzyme that catalyzes the carboxylation of glutamate residues in vitamin K-dependent proteins involved in blood coagulation and bone metabolism. |
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| ln Vitro |
In this study, researchers have studied the effects of site-directed mutations in Escherichia coli nitrate reductase A (NarGHI) on heme reduction by a menaquinol analogue (menadiol) using the stopped-flow method. For NarGHIH66Y and NarGHIH187Y, both lacking heme bL but having heme bH, the heme reduction by menadiol is abolished. For NarGHIH56R and NarGHIH205Y, both without heme bH but with heme bL, a smaller and slower heme reduction compared to that of the wild-type enzyme is observed. These results indicate that electrons from menadiol oxidation are transferred initially to heme bL. A transient species, likely to be associated with a semiquinone radical anion, was generated not only on reduction of the wild-type enzyme as observed previously ( 1) but also on reduction of NarGHIH56R and NarGHIH205Y. The inhibitors 2-n-heptyl-4-hydroxyquinoline-N-oxide and stigmatellin both have significant effects on the reduction kinetics of NarGHIH56R and NarGHIH205Y. We have also investigated the reoxidation of menadiol-reduced heme by nitrate in the mutants. Compared to the wild type, no significant heme reoxidation is observed for NarGHIH56R and NarGHIH205Y. This result indicates that a single mutation removing heme bH blocks the electron-transfer pathway from the subunit NarI to the catalytic dimer NarGH[1].
In vitro, menadiol demonstrates 2.5× greater retention of vitamin K activity compared to other vitamin K analogs. It functions as an electron donor for reversed oxidative phosphorylation in submitochondrial particles. Menadiol is used as a model compound for studying vitamin K metabolism and function. The compound shows concentration-dependent activity in biochemical assays. Its conversion to MK-4 can be studied in hepatocyte cultures to investigate vitamin K metabolism pathways. |
| ln Vivo |
In vivo, menadiol acts as a prodrug that is converted in the liver to menaquinone-4 (MK-4), the biologically active form of vitamin K. MK-4 serves as a cofactor for γ-glutamyl carboxylase, which is essential for the post-translational modification of vitamin K-dependent proteins. These proteins include coagulation factors (II, VII, IX, X) and bone matrix proteins (osteocalcin). Menadiol has been used in nutritional and metabolic studies to investigate vitamin K physiology and requirements.
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| Enzyme Assay |
To investigate the reoxidation of the menadiol-reduced hemes in NarGHI by nitrate, a sequential mixing method was utilized. In this method, 1 mg mL-1 NarGHI or mutant in 100 mM MOPS and 5 mM EDTA (pH 7.0) was first rapidly mixed with an equal volume of 500 μM menadiol in the same buffer. After being aged for 50 s to allow the complete reduction of the hemes, this mixture was then rapidly mixed with an equal volume of 1 mM nitrate, and the reoxidation process was followed at 560 nm.In both single and sequential mixing experiments, at least three runs were performed for each time scale and 2000 data points were collected at both wavelengths of 560 and 575 nm (as reference). The raw data were averaged, and the data for the reduction or reoxidation of the hemes were obtained by subtracting the reference data collected at 575 nm from the data obtained at 560 nm. The background absorbance from LCB2048 membranes lacking NarGHI was also subtracted from these data. After subtraction, the data were fitted to an appropriate equation using the software supplied by Applied Photophysics. The absorbance changes observed for the reduction of hemes by menadiol (ΔAbs) were fitted to a double-exponential equation[1].
The in vitro enzyme assay for menadiol typically involves measuring the activity of vitamin K-dependent carboxylase or the conversion of menadiol to menaquinone-4. Microsomal fractions from liver or recombinant enzymes are incubated with menadiol and other cofactors (e.g., reduced vitamin K, CO₂) in assay buffer at 37°C. Carboxylase activity is measured by the incorporation of [¹⁴C]-CO₂ into peptide substrates. For reversed oxidative phosphorylation studies, submitochondrial particles are incubated with menadiol and electron acceptors. |
| Cell Assay |
For in vitro cell-based assays, hepatocytes or other cell lines are cultured and treated with menadiol at concentrations ranging from 0.1-100 µM for 4-24 hours. Menadiol conversion to MK-4 is measured by HPLC or LC-MS/MS. Vitamin K-dependent protein carboxylation is assessed by Western blot using specific antibodies. Cell viability is assessed using MTT or CCK-8 assays. Oxidative stress markers may be measured in mitochondrial studies.
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| Animal Protocol |
In vivo animal studies for menadiol are conducted in the context of vitamin K metabolism and nutritional research. Menadiol is administered to rodents via oral gavage or dietary supplementation at doses ranging from 0.1-10 mg/kg. Tissue levels of menadiol and MK-4 are measured by LC-MS/MS. Vitamin K-dependent protein carboxylation is assessed in liver and bone tissues. Coagulation parameters such as prothrombin time are measured.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of menadiol have been characterized in nutritional studies. The molecular weight is 174.20 g/mol and the molecular formula is C₁₁H₁₀O₂. After oral administration, menadiol is absorbed and undergoes hepatic alkylation to form menaquinone-4 (MK-4). MK-4 distributes to various tissues including liver, bone, and brain. The compound has a relatively short half-life and is excreted primarily as metabolites.
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| Toxicity/Toxicokinetics |
Oral LD50 in mice: 30 mg/kg, Journal of Pharmacology and Experimental Therapeutics, 75(111), 1942. Intraperitoneal injection of LDLo in mice: 400 mg/kg, Journal of the French Biological Society, 143(585), 1949. Subcutaneous injection of LDLo in mice: Behavior: lethargy (reduced overall activity); Lung, pleural, or respiratory: dyspnea, Journal of Pharmacology and Experimental Therapeutics, 71(210), 1941.
Toxicology data for menadiol are limited. As a vitamin K analog, the compound is generally considered to have low toxicity at physiological doses. However, high doses may cause hemolytic anemia and liver toxicity. The compound is not intended for human use as a therapeutic agent. Standard laboratory safety precautions should be followed when handling the compound. |
| References |
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| Additional Infomation |
Menaadiol is a naphthalene-1,4-diol with a methyl substituent at the 2-position. It belongs to the naphthalenediol, methylnaphthalene, and naphthoquinone classes of compounds. Its function is related to that of naphthalene-1,4-diol. Menaadiol is a metabolite of Escherichia coli (strains K12 and MG1655). See also: Menaquinone (note moved to).
Menadiol (Dihydrovitamin K3) is a menaquinol analogue and vitamin K prodrug that is converted in the liver to menaquinone-4 (MK-4). It demonstrates 2.5× greater retention of vitamin K activity compared to other analogs and serves as an electron donor for reversed oxidative phosphorylation. Menadiol is a valuable research tool for studying vitamin K metabolism, mitochondrial function, and coagulation biology. It is intended for research use only and is not approved for therapeutic applications. |
| Molecular Formula |
C11H10O2
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| Molecular Weight |
174.20
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| Exact Mass |
174.068
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| CAS # |
481-85-6
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| PubChem CID |
10209
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| Appearance |
Pale purple to purple solid powder
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| Density |
1.274g/cm3
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| Boiling Point |
391.6ºC at 760mmHg
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| Melting Point |
181℃
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| Flash Point |
199.5ºC
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| Vapour Pressure |
1.08E-06mmHg at 25°C
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| Index of Refraction |
1.697
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| LogP |
2.559
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
13
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| Complexity |
181
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C2=CC=CC=C2C(=C1)O)O
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| InChi Key |
ZJTLZYDQJHKRMQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H10O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6,12-13H,1H3
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| Chemical Name |
2-methylnaphthalene-1,4-diol
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| Synonyms |
Menadiol; 481-85-6; 2-Methylnaphthalene-1,4-diol; 2-Methyl-1,4-naphthohydroquinone; Dihydrovitamin K3; Reduced menadione; 2-Methyl-1,4-naphthalenediol; Vitamin K3H2;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (574.05 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.7405 mL | 28.7026 mL | 57.4053 mL | |
| 5 mM | 1.1481 mL | 5.7405 mL | 11.4811 mL | |
| 10 mM | 0.5741 mL | 2.8703 mL | 5.7405 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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