Vitamin K (28-18-7) Physical and Chemical Properties
Vitamin K
A fat‑soluble 1,4‑naphthoquinone used as an active pharmaceutical ingredient and nutritional supplement component, commonly specified and handled by formulation, QC and procurement teams.
| CAS Number | 28-18-7 |
| Family | 1,4‑Naphthoquinones (Vitamin K family) |
| Typical Form | Lipophilic viscous oil (light‑sensitive) |
| Common Grades | EP, JP, USP |
Vitamin K (phylloquinone, a form of vitamin K1) is a fat‑soluble naphthoquinone derivative belonging to the 1,4‑naphthoquinone structural class. The core scaffold is a 1,4‑naphthoquinone (naphthalenedione) ring system substituted by a methyl group and a long, branched phytyl side chain bearing multiple methyl groups and a single double bond in the (E) configuration. The electronic structure combines an extended aromatic/quinone π system on the bicyclic ring with a nonpolar, aliphatic terpenoid tail; this produces a molecule that is strongly lipophilic while retaining two carbonyl oxygen atoms capable of acting as hydrogen‑bond acceptors and redox partners in enzymatic cycles.
Because of the long alkyl side chain and low polar surface area, vitamin K1 is essentially neutral at physiological pH (formal charge 0) and displays very high partitioning into lipophilic phases. Acid–base behavior is minimal under ordinary conditions (no ionizable groups in the physiological pH range), but the quinone core participates in reversible redox chemistry (quinone ⇄ semiquinone ⇄ hydroquinone) that is central to its biochemical function. Photochemical and oxidative degradation pathways are important: the phytyl side chain and quinone ring predispose the compound to photodecomposition and to redox cycling under pro‑oxidant conditions; conversely, hydrolysis is not a dominant pathway for the intact phylloquinone molecule in neutral aqueous media due to the lipophilic side chain.
Industrial and pharmaceutical relevance is substantial: phylloquinone is used therapeutically to prevent and treat vitamin K deficiency and as an antidote to coumarin anticoagulants; it is also added to foods and dietary supplements as a nutrient supplement and occurs naturally in green plants. Common commercial grades reported for this substance include: EP, JP, USP.
Molecular Overview
Molecular Weight and Composition
- Molecular formula: C31H46O2
- Molecular weight: \(450.7\ \mathrm{g}\,\mathrm{mol}^{-1}\)
- Exact mass (monoisotopic): \(450.349780706\ \mathrm{Da}\)
- Heavy atom count: 33
The molecule combines a relatively high molar mass for a small vitamin with an extended hydrophobic terpenoid chain that dominates bulk properties (density in organic matrices, low aqueous solubility). The low topological polarity (see below) is consistent with strong partitioning into lipidic compartments and micellar systems.
Charge, Polarity, and LogP
- Formal charge: 0
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 2
- Topological polar surface area (TPSA): \(34.1\ \text{Å}^2\)
- XLogP3‑AA: 10.9
The combination of zero formal charge, negligible hydrogen‑bond donor capacity, low TPSA, and very high XLogP indicates extreme lipophilicity. In practical terms, phylloquinone will be insoluble or very sparingly soluble in water, will partition strongly into oils, biological membranes and lipoproteins, and its absorption from the gut requires bile salts for micellar solubilization.
Biochemical Classification
- Chemical class: 1,4‑naphthoquinone (benzoquinones, fused)
- Pharmaceutical classification: Vitamin (fat‑soluble); essential cofactor in gamma‑carboxylation of blood coagulation proteins
Phylloquinone functions as a lipid‑bound cofactor in the vitamin K cycle; its quinone/hydroquinone interconversions are exploited by enzymatic systems (gamma‑glutamyl carboxylase and vitamin K epoxide reductase) to generate the reduced cofactor needed for post‑translational carboxylation of specific glutamate residues.
Chemical Behavior
Stability and Degradation
Phylloquinone is generally stable to air and moisture but is susceptible to photodecomposition and oxidative degradation. The conjugated quinone system can undergo one‑electron reduction to a semiquinone radical and two‑electron reduction to the hydroquinone; these redox transitions are central to enzymatic activity but also render the molecule susceptible to undesired redox cycling under oxidative stress. Photolysis of the phytyl side chain and ring substituents leads to loss of potency and to formation of oxidized or fragmented products; therefore, material should be protected from light to maintain stability.
Thermal and hydrolytic stability are relatively high for the intact molecule in nonreactive media, but interaction with strong oxidants or strong bases can promote ring opening or substitution at activated positions on the quinone ring.
Hydrolysis and Transformations
No significant hydrolysis of the phytyl ester (there is none) occurs under physiological conditions; instead, metabolic and chemical transformations proceed via redox and alkylation/dealkylation reactions. Biochemically, phylloquinone is reduced to the hydroquinone form to serve as the active cofactor in gamma‑glutamyl carboxylation and is oxidized to the epoxide during catalysis; vitamin K epoxide reductase then regenerates the active reduced form. Microbial and chemical hydrogenation/oxidation can convert phylloquinone into a variety of menaquinone‑type structures or fragmented metabolites. The semiquinone radical is a known intermediate and can participate in one‑electron transfer reactions.
Biological Role
Functional Role and Pathways
Phylloquinone is an essential lipid cofactor for the gamma‑carboxylase enzymes that catalyze post‑translational gamma‑carboxylation of glutamic acid residues in several clotting factors (notably factors II, VII, IX and X) and regulatory proteins (protein C, protein S, protein Z). Gamma‑carboxylation introduces γ‑carboxyglutamate (Gla) residues that confer calcium‑binding capacity, which is required for proper membrane localization and activity of these factors within the coagulation cascade.
The vitamin K cycle (quinone → hydroquinone → epoxide → quinone) couples redox chemistry to enzymatic carboxylation and necessitates specific reductases, including vitamin K epoxide reductase, to regenerate the reduced cofactor.
Physiological and Cellular Context
Absorption: oral absorption of phylloquinone is efficient only in the presence of bile salts and dietary lipids that enable micellar solubilization. After absorption, the vitamin is initially taken up and concentrated in the liver, the principal site of synthesis for vitamin K‑dependent clotting factors; tissue accumulation outside of the liver is low. Route of elimination: almost no free unmetabolized vitamin K is typically observed in bile or urine, consistent with extensive hepatic metabolism. Clinically, prophylactic intramuscular or oral administration of phylloquinone is standard to prevent vitamin K deficiency bleeding in newborns; deficiency in adults can arise from malabsorption or poor nutrition and results in impaired clotting and increased bleeding risk.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS (primary shown in header): 28-18-7
- Other CAS numbers appearing in associated records: 84-80-0; 12001-79-5; 27696-10-2; 81818-54-4; 2581046-19-5; 10485-69-5
- InChI: InChI=1S/C31H46O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+
- InChIKey: MBWXNTAXLNYFJB-LKUDQCMESA-N
- SMILES: CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(\C)/CCCC(C)CCCC(C)CCCC(C)C
- KEGG IDs: C02059; D00148
- ChEBI: CHEBI:94399
- ChEMBL: CHEMBL520156
- NSC Number: 270681
- European Community (EC) Number: 234-408-7
These identifiers provide cross‑referencing between chemical registries and cheminformatics resources and are useful for procurement, QC, and analytical method set‑up.
Synonyms and Biological Names
Common synonyms and names (selected from deposited synonym lists) include:
- Vitamin K
- Phylloquinone
- Phytomenadione
- Phytonadione (INN)
- Phytylmenadione
- Phytomenadione/Vitamin K1 (Mixture of Trans Racemic & Cis Racemic)
- Mephyton (TN)
- Phytomenadione (Phytomenadione; Phytonadione)
- Vitamin K semiquinone radical
These synonyms reflect clinical, pharmacopoeial and chemical naming used in pharmaceutical and nutritional contexts.
Safety and Handling Overview
Handling and Storage of Biochemical Materials
- Physical hazards and PPE: As a lipophilic, nonvolatile organic solid, phylloquinone presents low inhalation risk in bulk form but may generate dust; use standard PPE (gloves, eye protection, lab coat) and engineering controls to minimize dust exposure. Avoid generation of airborne particles.
- Fire and reactivity: The compound is organic and combustible; store away from strong oxidizers and open flames. In bulk handling, follow standard precautions for combustible organic solids.
- Photostability and storage: Protect from light to minimize photodecomposition. Store in a cool, dry place, in tightly closed containers under inert atmosphere if long‑term storage or storage at elevated temperatures is anticipated.
- Spill and waste handling: Recover material for reuse where appropriate or collect for disposal as organic chemical waste per local regulations; avoid release into waterways due to lipophilicity and persistence in nonpolar compartments.
- Clinical/toxicology notes: Toxicity from phylloquinone and menaquinones (K1/K2) is rare; adverse effects have been reported for synthetic menadione (vitamin K3) which is associated with hemolytic anemia and hepatotoxicity and is not used for routine human supplementation. Intravenous administration of phylloquinone has been associated with rare severe hypersensitivity reactions (bronchospasm, cardiac events). LD50 data reported in associated experimental summaries include: \(41.5\,\mathrm{mL}\,\mathrm{kg}^{-1}\) at 0.2% (Intravenous, Mouse) and \(52\,\mathrm{mL}\,\mathrm{kg}^{-1}\) at 1% (Intravenous, Mouse) — these values reflect specific formulations and routes and should be interpreted in context of concentration and vehicle. For pregnancy and lactation, maternal supplementation increases breastmilk concentrations but neonatal prophylactic administration to newborns remains the established and recommended method to prevent vitamin K deficiency bleeding.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and comply with applicable local legislation.
Handling and Storage of Biochemical Materials
Material management in manufacturing or laboratory settings should account for the compound's lipophilicity and light sensitivity. Typical good practices include:
- Storage in amber or opaque containers to exclude light.
- Storage at controlled, cool temperatures to slow oxidative degradation.
- Minimizing exposure to air and moisture when possible; for longer‑term storage, inert gas blanketing reduces oxidative loss.
- Use of antioxidants or stabilizers is sometimes applied in formulated products, but their selection must be validated for compatibility with intended use.
- In production and QC, analytical methods (e.g., LC‑MS with APCI in positive mode) are effective for identity and purity testing; mass spectrometric data show prominent molecular ion signals at \(m/z\) 451.357 (positive ion [M+H]+) under typical APCI‑QTOF conditions.
For regulatory classification, safe transport and disposal, consult the SDS and local regulatory guidance; do not assume transport classifications without supplier documentation.
