Quantum-designed Triple Chelate Complex of Iron, Ascorbic Acid and Vitamin B6: Complementary Stability Profiles and Colloidal Integration into Milk Micellar Systems

Abstract

Iron deficiency remains a global health challenge, necessitating novel formulations with enhanced bioavailability and food matrix compatibility. This study rationally designs triple iron(II)-ascorbate-vitamin B6 chelates using pyridoxine (complex 1) and pyridoxamine (complex 2) ligands. Density functional theory predicts complementary stability profiles: both complexes offer thermodynamic favorability (ΔE = -1258 kcal/mol for complex 1, -1246 kcal/mol for complex 2) and enhanced chemical hardness (η = 0.139 eV for complex 1, 0.152 eV for complex 2). UV-Vis and FTIR confirm distinct O, O/N-donor coordination, with pyridoxamine exhibiting stronger Fe–N bonding. X-ray diffraction analysis demonstrated that both chelate complexes incorporating different forms of vitamin B₆ are amorphous and exhibit no long-range crystalline order, unlike the crystalline organic ligands used for their synthesis. Thermal analysis further confirmed the formation of new coordination ionic compounds, as the endothermic and exothermic transitions observed for the complexes were markedly distinct from those of the free ligands. Ternary response surfaces reveal both complexes maintain stability across physiological pH, with complex 2 showing broader processing tolerance. Milk fortification across 10–100% iron recommended daily allowance doses preserves colloidal integrity: pH shifts < 0.2 units, conductivity rises linearly + 10%, hydrodynamic radius remains within ± 5% of control, while titratable acidity and surface tension show no variation. Unlike free iron salts inducing 20–50% casein micelle aggregation, both chelates function as colloidally inert fortificants. The stability of the complexes under conditions simulating the gastric environment was evaluated at pH 2; optical spectroscopy revealed that the characteristic absorption bands of the complexes remained intact, indicating their stability in an acidic medium. These findings establish dual-platform iron delivery for dairy fortification, bridging coordination chemistry and colloidal food science.