As an organic acid salt formed by divalent iron (Fe²⁺) and gluconate, the stable structure of ferrous gluconate primarily relies on the coordination between Fe²⁺ and gluconate. When gluconic acid (HOCH₂(CHOH)₄COOH) acts as a ligand, it does not participate in binding in its complete molecular form. Instead, it first dissociates into gluconate ions (HOCH₂(CHOH)₄COO⁻), which then form coordination bonds with Fe²⁺ through specific functional groups. This process is accompanied by the synergistic effects of intramolecular hydrogen bonds and spatial configuration, ultimately resulting in the formation of a stable coordination compound. Its binding mode can be analyzed from four aspects: ligand dissociation, coordination sites, coordination structure, and stability regulation.
I. Predissociation of Gluconic Acid: Formation of the Active Ligand Form
Gluconic acid is a polyhydroxy organic acid containing 6 carbon atoms, with the carboxyl group (-COOH) at the end of its molecule serving as the key acidic group (pKa ≈ 3.9 at 25°C). In aqueous solutions or neutral-to-weakly alkaline environments, the carboxyl group easily undergoes proton dissociation, releasing H⁺ and converting into a carboxylate anion (-COO⁻)—this dissociation process is a prerequisite for gluconic acid to bind with Fe²⁺.
The dissociated gluconate ion not only carries a negative charge but also possesses the potential for "multifunctional group synergy" due to the presence of 5 hydroxyl groups (-OH) in its molecule. Although hydroxyl groups do not directly participate in proton dissociation, the lone pairs of electrons on hydroxyl oxygen atoms can assist in coordination. Meanwhile, the polarity of hydroxyl groups can stabilize the final coordination structure through hydrogen bonds. Therefore, gluconate is not a simple monodentate ligand but a polydentate ligand precursor with both "primary coordination sites" and "auxiliary stability sites."
II. Core Coordination Sites: Dominant Role of Carboxylate Anions
As a transition metal ion, Fe²⁺ has an electron configuration of 3d⁶, exhibiting a strong ability to accept lone pairs of electrons, with common coordination numbers of 4 (tetrahedral configuration) or 6 (octahedral configuration). In its binding with gluconate, the oxygen atoms of carboxylate anions serve as the primary coordination sites: the -COO⁻ group at the end of gluconate has two equivalent oxygen atoms (due to resonance, the negative charge is evenly distributed between the two oxygen atoms), and each oxygen atom has a lone pair of electrons that can form a σ coordination bond with the empty orbitals of Fe²⁺.
From the perspective of coordination modes, the -COO⁻ group of a single gluconate ion typically binds to Fe²⁺ in two ways: monodentate coordination or chelating bidentate coordination:
In monodentate coordination, only one carboxylate oxygen atom forms a bond with Fe²⁺. In this case, Fe²⁺ needs to bind to multiple gluconate ions to meet its coordination number requirement.
In chelating bidentate coordination, the two carboxylate oxygen atoms of the same gluconate ion respectively form bonds with Fe²⁺, creating a stable five-membered or six-membered chelate ring (Fe²⁺-O-C-O-C ring structure). The formation of chelate rings significantly enhances the stability of the coordination compound (chelate effect).
Thus, in the actual structure of ferrous gluconate, chelating bidentate coordination is the dominant binding mode—and this is the core reason why ferrous gluconate is more stable and less irritating than inorganic ferrous salts (e.g., ferrous sulfate).
III. Auxiliary Coordination and Spatial Configuration: Synergistic Stabilizing Effect of Hydroxyl Groups
In addition to carboxyl groups, the 5 hydroxyl groups (-OH) in the gluconate molecule do not directly form strong coordination bonds. However, the lone pairs of electrons on hydroxyl oxygen atoms can form weak coordination interactions (secondary coordination) with the empty orbitals of Fe²⁺, or interact with hydroxyl and carboxylate oxygen atoms of other gluconate ions through hydrogen bonds—further optimizing the spatial configuration and stability of the coordination structure.
In terms of spatial configuration, the coordination between Fe²⁺ and gluconate usually forms an octahedral structure:
Fe²⁺ is located at the center of the octahedron. Among the 6 coordination sites, 2–4 sites are occupied by carboxylate oxygen atoms of gluconate (via bidentate chelation or monodentate coordination), while the remaining sites may be supplemented by water molecules (H₂O) or hydroxyl oxygen atoms of other gluconate ions.
The presence of hydroxyl groups also prevents Fe²⁺ from binding to other impurity ions (e.g., OH⁻) through the "steric hindrance effect": the long-chain polyhydroxy structure of gluconate forms a "spatial barrier" around Fe²⁺, reducing the probability of Fe²⁺ coming into contact with external OH⁻ and thereby inhibiting the hydrolysis of Fe²⁺ (this is also an important reason why ferrous gluconate is less likely to precipitate than ferrous sulfate in neutral environments). Additionally, intramolecular hydrogen bonds between hydroxyl groups (e.g., O-H…O bonds formed between hydroxyl oxygen and hydrogen atoms of adjacent gluconate ions) can further fix the conformation of the coordination structure, lower the molecular energy state, and enhance overall stability.
IV. Coordination Ratio and Stability: Matching of Charge Balance and Coordination Number
The coordination ratio of ferrous gluconate (molar ratio of Fe²⁺ to gluconate) is determined by the charge of Fe²⁺, the charge of gluconate, and the coordination number of Fe²⁺. Fe²⁺ carries a +2 charge, and each gluconate ion carries a -1 charge. From the perspective of charge balance, one Fe²⁺ ion needs to bind to two gluconate ions to achieve electrical neutrality (i.e., a coordination ratio of 1:2).
This coordination ratio is also compatible with the coordination number of Fe²⁺:
If both gluconate ions bind via bidentate chelation, they provide exactly 4 coordination sites, and the remaining 2 sites can be occupied by water molecules—forming a six-coordinate octahedral structure of "2 gluconate ions + 2 water molecules."
If some gluconate ions bind via monodentate coordination, more gluconate ions would be required. However, based on the principle of minimum energy, the 1:2 coordination ratio is the most stable form, as it simultaneously satisfies both charge balance and the chelate effect.
The stability of this coordination mode is also reflected in its "anti-dissociation ability": compared with inorganic ferrous salts (e.g., ionic bond binding between Fe²⁺ and SO₄²⁻), the coordination bond between Fe²⁺ and gluconate exhibits both ionic and covalent characteristics (the lone pairs of electrons on oxygen atoms partially overlap with the empty orbitals of Fe²⁺, forming partial covalency). This higher bond energy prevents easy dissociation into free Fe²⁺ in aqueous solutions, which not only reduces direct contact between Fe²⁺ and the gastrointestinal mucosa (lowering irritation) but also avoids the oxidation of Fe²⁺ to Fe³⁺ (improving bioavailability)—these are the core advantages of ferrous gluconate as an oral iron supplement.
The binding between Fe²⁺ and gluconic acid in ferrous gluconate is a continuous process: "gluconic acid dissociates into gluconate ions → carboxylate anions dominate coordination (monodentate or bidentate chelation) → hydroxyl groups assist in stabilization (secondary coordination + hydrogen bonds + steric hindrance) → stable structure formation via charge and coordination number matching." This binding mode not only leverages the strong coordination ability of carboxyl groups to ensure bonding stability but also optimizes the spatial configuration through the synergistic effect of hydroxyl groups. Ultimately, it achieves efficient stabilization of Fe²⁺, laying a chemical foundation for its application in the pharmaceutical and food industries.
