Ferrous Gluconate (299-29-6) Physical and Chemical Properties

Chemical Profile

Ferrous Gluconate

Iron(II) gluconate supplied as a dry solid, commonly used as a source of iron for food fortification, dietary supplement and oral pharmaceutical formulations.

CAS Number	299-29-6
Family	Iron(II) gluconates
Typical Form	Powder or granules
Common Grades	EP, Food Grade, USP

Used by manufacturers and formulators for food fortification, nutritional supplements and oral pharmaceutical products; procurement typically targets specified grades for assay, moisture and heavy metal limits. Attention to oxidation, moisture control and particle-size distribution is important for shelf life, blending performance and QC testing (iron assay, moisture, appearance).

Ferrous gluconate is an organic iron(II) salt formed by coordination of a divalent iron cation to two gluconate anions (D-gluconate derived from glucose). Structurally it is best described as iron(2+);bis((2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoate): a 1:2 metal-to-ligand complex in which each gluconate provides oxyanion donor atoms to chelate Fe(II). The compound exists as a covalently discrete assembly of three covalently-bonded units (two gluconate moieties and one Fe2+) and is stereochemically defined (eight defined atom stereocenters). The coordination environment and multiple hydroxyl/carboxylate groups produce very high polar surface area and extensive hydrogen-bonding capacity in the solid state and in solution.

Electronically, the iron center is in the +2 oxidation state and the ligands are present predominantly as carboxylate/alkoxide-type donor sites; the overall neutral assembly (formal charge 0) reflects internal charge balance between Fe(II) and two singly deprotonated gluconate anions. Because Fe(II) is susceptible to aerobic oxidation to Fe(III), solutions and neutral to alkaline pH conditions favor conversion to ferric species; this redox lability strongly influences color, stability and precipitation behavior. The high topological polar surface area, numerous hydrogen-bond donors/acceptors and absence of lipophilic motifs produce a highly water‑soluble, hydrophilic salt with negligible intrinsic lipophilicity relative to neutral organic small molecules.

Ferrous gluconate is widely used industrially and pharmaceutically as an oral source of bioavailable iron (hematinic) and as a food additive/colorant (for example in specific applications such as ripe-olive color treatment). It is formulated for dietary supplementation, animal feed fortification and oral medicinal products where Fe(II) bioavailability and tolerability are required. Common commercial grades reported for this substance include: EP, Food Grade, USP.

Basic Physical Properties

Dry material is described as a pale greenish‑yellow to yellowish‑grey powder or granules and may exhibit a faint odour reminiscent of burnt sugar or caramel. The solid is a dry powder under ambient conditions and is typically handled as such in manufacturing and formulation operations.

The visual color of aqueous solutions is pH dependent: light yellow at \(\mathrm{pH}\) 2, brown at \(\mathrm{pH}\) 4.5 and green at \(\mathrm{pH}\) 7. The observed color change reflects pH‑dependent speciation and partial oxidation of Fe(II) to Fe(III).

Solubility and Hydration

• Solubility: "Soluble with slight heating in water. Practically insoluble in ethanol." A specific experimental solubility note states: "1 gram dissolves in about 10 ml of water with slight heating and in 1.3 ml of water at \(100\,^\circ\mathrm{C}\). It forms supersaturated solutions which are stable for a period of time."
• Soluble in glycerin; glycerin also retards oxidation of the ferrous ion in solution.
• Solubility is increased by addition of citric acid or citrate ion; conversely, in neutral solutions soluble carbonates, phosphates and oxalates can produce precipitation (common behavior for ferrous salts forming sparingly soluble secondary phases).
• Hydration state: a commonly encountered form is the dihydrate; the dihydrate form influences melting/decomposition behaviour and solubility.

Thermal Stability and Decomposition

• Melting/Decomposition: "The melting point for D-gluconic acid, ferrous salt dihydrate (98%) is 188 \(\,^\circ\mathrm{C}\), decomposes." Thermal decomposition of the salt yields acrid smoke and irritating fumes; combustion/decomposition products are potentially corrosive and irritating.
• Aqueous stability is strongly pH‑dependent: approximately neutral solutions undergo rapid oxidation of Fe(II) to Fe(III); stability is improved by buffering to \(\mathrm{pH}\) 3.5–4.5 (citrate buffer recommended) and by addition of antioxidants or stabilizers (e.g., glucose, glycerin).

Chemical Properties

Ferrous gluconate behaves as a coordination chelate of Fe(II) with two gluconate ligands; its chemical properties are dominated by metal‑ligand coordination, redox chemistry of iron, and extensive hydrogen bonding from multiple hydroxyl groups.

Complex Formation and Coordination

• IUPAC/structural descriptor: "iron(2+);bis((2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoate)". The gluconate ligands coordinate through oxyanion donor atoms (carboxylate and adjacent oxygen atoms), producing a chelated Fe(II) center.
• The compound is effectively a bidentate chelate per gluconate (commonly annotated as O1,O2 coordination modes), yielding a neutral metal salt with internal charge balance.
• Chelation stabilizes the Fe(II) oxidation state to some extent in acidic, protected media; however, Fe(II) remains susceptible to aerobic oxidation, particularly at higher \(\mathrm{pH}\).

Reactivity and Stability

• Oxidation: Ferrous ion slowly oxidizes to ferric on exposure to air and is sensitive to light; oxidation is retarded by acidic buffering (optimal stability reported at \(\mathrm{pH}\) 3.5–4.5) and by co‑formulants such as glucose or glycerin.
• Color/interaction indicators: Ascorbic acid and glycine‑type additives can influence color and stability; ascorbic acid and glycine descriptions indicate color changes (darkening) and increased stability in some formulations. Interaction with pyridoxine can produce green coloration.
• Precipitation: In neutral or alkaline media formation of insoluble iron carbonates, phosphates or oxalates is possible, leading to loss of soluble iron; many organic hydroxy acids (sugars, glycerin) hinder precipitation.
• Chemical incompatibilities and interactions: Concomitant ingestion or coadministration with certain drugs and minerals may affect absorption or pharmacodynamic effects (examples include decreased absorption of certain drugs or altered metal uptake described in clinical interaction studies).

Molecular Parameters

• Molecular formula: C12H22FeO14
• Molecular weight: \(446.14\ \mathrm{g}\,\mathrm{mol}^{-1}\)
• Exact mass / Monoisotopic mass: \(446.035891\)
• Topological polar surface area (TPSA): \(283\)
• Heavy atom count: \(27\)
• Complexity: \(165\)
• Formal charge: \(0\)
• Hydrogen bond donor count: \(10\)
• Hydrogen bond acceptor count: \(14\)
• Rotatable bond count: \(8\)
• Defined atom stereocenter count: \(8\)
• Covalently-bonded unit count: \(3\)

These computed descriptors reflect a large, highly polar coordination assembly with extensive hydrogen‑bonding potential and limited lipophilicity.

LogP and Ionization State

• No experimentally established value for this property is available in the current data context for logP.
• Ionization/speciation: the solid material is a neutral assembly of one Fe(II) and two deprotonated gluconate anions (net neutral). In aqueous solution the carboxylate moieties remain deprotonated under physiological pH, and the iron center remains as Fe(II) unless oxidized; \(\mathrm{pH}\)-dependent redox and complexation equilibria control speciation and solubility.

Identifiers and Synonyms

Registry Numbers and Codes

• CAS Registry Number: 299-29-6
• European Community (EC) Number: 206-076-3
• UNII: 781E2AXH0K
• DrugBank ID: DB14488
• NCI Thesaurus Code: C29048
• InChI: InChI=1S/2C6H12O7.Fe/c27-1-2(8)3(9)4(10)5(11)6(12)13;/h22-5,7-11H,1H2,(H,12,13);/q;;+2/p-2/t2*2-,3-,4+,5-;/m11./s1
• InChIKey: VRIVJOXICYMTAG-IYEMJOQQSA-L
• SMILES: C(C@HO)O.C(C@HO)O.[Fe+2]

Synonyms and Structural Names

Selected synonyms and depositor-supplied names (as recorded for this substance) include: - FERROUS GLUCONATE - Iron(II) Gluconate - Ferroglyconicum - Glucoferron - Iron gluconate - Gluconic acid iron salt - Iron(2+) gluconate (1:2) - D-gluconic acid, iron(2+) salt (2:1) - Iron digluconate - Iron, bis(D-gluconato-O1,O2)- - Ferrous gluconate anhydrous - Iron(2+) gluconate, anhydrous - Associated deprecated identifiers and alternate CAS listings are recorded historically but the primary CAS above applies.

Industrial and Commercial Applications

Ferrous gluconate is used where a soluble, relatively well‑tolerated source of ferrous iron is required and where chelation by a carbohydrate‑derived ligand minimizes gastrointestinal irritation relative to some inorganic salts.

Use as Salt Form or Excipient

• Pharmaceutical: used as an oral hematinic for prevention and treatment of iron‑deficiency anemia; formulated in syrups, elixirs, tablets and capsules. Typical pharmaceutical formulations include dosage forms that deliver elemental iron in the range illustrated by product examples (e.g., capsules 435 mg equivalent to 50 mg elemental iron; elixir 300 mg equivalent to 37.5 mg elemental iron; tablets 320 mg equivalent to 40 mg elemental iron).
• Food industry: used as a colorant and nutrient supplement (for example, specific authorization exists for use in ripe‑olive color treatment and as a nutrient supplement in foods); also used as a fortificant in food and animal feed.
• Feed and fortification: used as a trace mineral fortificant in animal feeds and in food fortification where bioavailability and organoleptic compatibility are important.
• Typical manufacturing methods: produced by metathesis or salt exchange reactions (e.g., from barium or calcium gluconate and ferrous sulfate) or by reaction of ferrous carbonate with gluconic acid in aqueous solution.

Common commercial grades reported for this substance include: EP, Food Grade, USP.

Representative Use Cases

• Oral iron supplements and syrups formulated for human and veterinary use where Fe(II) bioavailability and reduced gastrointestinal irritation are desired.
• Food additive applications as a colorant/nutrient supplement (use is restricted to specified food applications in regulatory frameworks).
• Fortification of staple foods and animal feeds where iron stabilization strategies (e.g., coformulation with ascorbic acid or stabilizing excipients) are applied to maintain solubility and bioavailability.

If a concise, product‑specific application summary is required for procurement or specification development, selection should be based on the functional properties described above (solubility, stability, elemental iron content, and formulation compatibility).

Safety and Handling Overview

Handling and hazard considerations are dominated by the fact that this substance supplies bioavailable iron and contains a redox‑active metal center; occupational exposures are managed as for soluble iron salts.

Toxicological Considerations

• Acute toxicity: reported non‑human toxicity values include LD50 (rat, oral) \(2237\,\mathrm{mg}\,\mathrm{kg}^{-1}\); LD50 (mouse, oral) \(3700\,\mathrm{mg}\,\mathrm{kg}^{-1}\); LD50 (mouse, iv) \(114\,\mathrm{mg}\,\mathrm{kg}^{-1}\); LD50 (mouse, ip) \(160\,\mathrm{mg}\,\mathrm{kg}^{-1}\).
• Regulatory hazard information: some notifications classify the substance with hazard statement H302 (Harmful if swallowed) and a signal word of "Warning" in specific product notifications. Reported classifications can vary with formulation, impurity profile and concentration.
• Clinical/toxic management: for suspected overdose, guidance includes airway and circulatory support, gastric lavage for significant ingestion or radiographic evidence of tablets, and consideration of chelation therapy with deferoxamine in severe poisoning (serum iron markedly elevated, shock, severe acidosis). Oral elemental iron ingestion above \(20\,\mathrm{mg}\,\mathrm{kg}^{-1}\) typically prompts more aggressive decontamination/clinical monitoring.
• Interactions: oral iron absorption and systemic interactions occur with multiple agents — e.g., reduced zinc absorption when large doses of iron are coadministered; interactions with methyldopa and salicylates have been observed in clinical and experimental contexts. Ascorbic acid (vitamin C) can enhance iron absorption when coadministered.
• Populations at risk: individuals with disorders of iron metabolism (e.g., hemochromatosis or related disorders impairing iron regulation) are at increased risk from excessive iron exposure; pediatric accidental ingestion of iron‑containing preparations is a recognized hazard.

Storage and Handling Guidelines

• Storage: store in a cool, dry, well‑ventilated area away from oxidizing agents and strong bases; protect from light and air exposure to reduce oxidative conversion of Fe(II) to Fe(III). Hydrated forms and bulk powders should be kept in tightly closed containers to limit moisture uptake and oxidation.
• Formulation/processing controls: use acidic or citrate buffers (preferred \(\mathrm{pH}\) range 3.5–4.5) and stabilizers (e.g., glucose, glycerin) in aqueous formulations to retard oxidation; avoid coformulation with incompatible anions that precipitate iron (carbonate, phosphate, oxalate) unless managed by chelating/stabilizing strategies.
• Occupational hygiene: control dust exposure (local exhaust ventilation, dust collection) and use appropriate PPE (gloves, eye protection); established occupational exposure limits for soluble iron salts are commonly \(1\,\mathrm{mg}\,\mathrm{m}^{-3}\) (8‑hour TWA) in many jurisdictions—implement monitoring and control measures accordingly.
• Packaging: keep in child‑proof and tamper‑resistant containers for formulations intended for oral administration; follow standard pharmaceutical packaging hygiene for drug products.
• Emergency measures: in case of spills, avoid generating dust, collect material for recovery or disposal in accordance with local regulations and prevent release to the environment.

For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and applicable local legislation.