Investigating the Kinetics of Cu²⁺-Catalyzed Oxidation of Ascorbic Acid (C₆H₈O₆) in Aqueous Solutions

Abstract

Ascorbic acid degrades rapidly in aerated aqueous media through catalysis by trace Cu²⁺, yet published rate constants remain fragmented across dissimilar conditions and complete activation parameters are unavailable. This study establishes an internally consistent kinetic description of this reaction. Progress was followed spectrophotometrically at 265 nm under pseudo-first-order conditions while ascorbic acid (2.0–12.0 × 10⁻⁵ mol L⁻¹), Cu²⁺ (4.0 × 10⁻⁶–1.0 × 10⁻⁴ mol L⁻¹), pH (3.0–6.0), ionic strength (0.01–0.50 mol L⁻¹ KNO₃) and temperature (288–318 K) were varied systematically. The reaction was first order in both substrate and catalyst, giving k_cat = 277 ± 8 L mol⁻¹ s⁻¹ at 298 K, pH 4.5 and I = 0.10 mol L⁻¹. The ascorbate monoanion was forty times more reactive than the neutral diacid, and a negative Brønsted–Bjerrum slope confirmed oppositely charged reactants in the rate-determining step. Normalising for dissolved oxygen raised the activation energy from 38.8 to 52.0 kJ mol⁻¹, with ΔS‡ = −76.4 J mol⁻¹ K⁻¹, indicating an associative inner-sphere pathway.

REFERENCES

[1] J. Kazmierczak-Baranska, K. Boguszewska, A. Adamus-Grabicka, and B. T. Karwowski, "Two faces of vitamin C Antioxidative and pro-oxidative agent," Nutrients, vol. 12, no. 5, art. no. 1501, 2020, doi: 10.3390/nu12051501.

[2] D. Guo, Y. Liao, J. Na, L. Wu, Y. Yin, Z. Mi, et al., "The involvement of ascorbic acid in cancer treatment," Molecules, vol. 29, no. 10, art. no. 2295, 2024, doi: 10.3390/molecules29102295.

[3] L. Feng, Y. Yang, Y. Xie, S. Liu, X. Peng, S. Hu, et al., "Kinetics of L-ascorbic acid degradation and non-enzymatic browning development in hot-compressed water," Front. Nutr., vol. 9, art. no. 1022254, 2023, doi: 10.3389/fnut.2022.1022254.

[4] M. J. Ho, D. W. Park, and M. J. Kang, "Design of novel tricaprylin-incorporated multi-layered liposomal system for skin delivery of ascorbic acid with improved chemical stability," Pharmaceuticals, vol. 16, no. 1, art. no. 121, 2023, doi: 10.3390/ph16010121.

[5] M. Caban, K. Lenard, A. Nowak, and A. Dzimitrowicz, "New method for quantification of ascorbic acid in fruit juices with an application of ionic liquids as phase modifier in reverse phase HPLC," Microchem. J., vol. 215, art. no. 114440, 2025, doi: 10.1016/j.microc.2025.114440.

[6] J. Shen, P. T. Griffiths, S. J. Campbell, B. Utinger, M. Kalberer, and S. E. Paulson, "Ascorbate oxidation by iron, copper and reactive oxygen species: Review, model development, and derivation of key rate constants," Sci. Rep., vol. 11, art. no. 7417, 2021, doi: 10.1038/s41598-021-86477-8.

[7] A. E. Murekhina, D. N. Yarullin, M. A. Sovina, P. A. Kitaev, and G. A. Gamov, "Copper(II)-catalyzed oxidation of ascorbic acid: Ionic strength effect and analytical use in aqueous solution," Inorganics, vol. 10, no. 7, art. no. 102, 2022, doi: 10.3390/inorganics10070102.

[8] M. Ferrer, A. N. Pham, and T. D. Waite, "Kinetic modeling assisted analysis of vitamin C-mediated copper redox transformations in aqueous solutions," J. Phys. Chem. A, vol. 127, no. 50, pp. 10663–10680, 2023, doi: 10.1021/acs.jpca.3c05736.

[9] A. Expósito, J. Maillo, I. Uriarte, M. Santibáñez, and I. Fernández-Olmo, "Kinetics of ascorbate and dithiothreitol oxidation by soluble copper, iron, and manganese, and 1,4-naphthoquinone: Influence of the species concentration and the type of fluid," Chemosphere, vol. 361, art. no. 142435, 2024, doi: 10.1016/j.chemosphere.2024.142435.

[10] M. Lin and J. Z. Yu, "Assessment of interactions between transition metals and atmospheric organics: Ascorbic acid depletion and hydroxyl radical formation in organic-metal mixtures," Environ. Sci. Technol., vol. 54, no. 3, pp. 1431–1442, 2020, doi: 10.1021/acs.est.9b07478.

[11] M. Ferrer, A. N. Pham, and T. D. Waite, "Optimising pollutant degradation in reductant-mediated copper Fenton-like systems using mechanistically-based kinetic modelling," Water Res., vol. 287, art. no. 124339, 2025, doi: 10.1016/j.watres.2025.124339.

[12] R. Jiang, Y. Sui, J. Hong, M. Niimi, Q. Yan, Z. Shi, et al., "The combined administration of vitamin C and copper induces a systemic oxidative stress and kidney injury," Biomolecules, vol. 13, no. 1, art. no. 143, 2023, doi: 10.3390/biom13010143.

[13] M. H. Ratner and J. S. Rutchik, "A rare case of early onset Lewy body dementia with parkinsonism associated with chronic exposure to copper contaminated drinking water," Front. Toxicol., vol. 6, art. no. 1451235, 2024, doi: 10.3389/ftox.2024.1451235.

[14] S. Ahmad, J. Ärnlöv, and S. C. Larsson, "Genetically predicted circulating copper and risk of chronic kidney disease: A Mendelian randomization study," Nutrients, vol. 14, no. 3, art. no. 509, 2022, doi: 10.3390/nu14030509.

[15] Q. Han, X. Chen, K. Li, H. Huang, and Y. Li, "Copper-based nanozymes for environmental analytical applications: A review," Trends Environ. Anal. Chem., vol. 48, art. no. e00281, 2025, doi: 10.1016/j.teac.2025.e00281.

[16] G. A. Gamov, D. N. Yarullin, M. A. Gudyrina, E. I. Pogodina, A. S. Medvedeva, and M. N. Zavalishin, "Protonation of L-ascorbic acid in an aqueous solution at T = 298.2 K, p = 0.1 MPa, and I = 0.10–5.0 mol L⁻¹ (NaCl)," J. Chem. Eng. Data, vol. 67, no. 6, pp. 1358–1364, 2022, doi: 10.1021/acs.jced.2c00034.

[17] L. Malacaria and E. Furia, "Wide pH range potentiometric and spectrophotometric investigation into the acidic constants of quercetin, luteolin and L-ascorbic acid in aqueous media," Appl. Sci., vol. 13, no. 2, art. no. 776, 2023, doi: 10.3390/app13020776.

[18] A. G. Ritacca, L. Malacaria, E. Sicilia, E. Furia, and G. Mazzone, "Experimental and theoretical study of the complexation of Fe³⁺ and Cu²⁺ by L-ascorbic acid in aqueous solution," J. Mol. Liq., vol. 355, art. no. 118973, 2022, doi: 10.1016/j.molliq.2022.118973.

[19] B. B. de Menezes, L. M. Frescura, D. Schein, M. Zadra, and M. B. da Rosa, "Reviewing the effect of metal complexation upon the antioxidant/antiradical properties of L-ascorbic acid," Ciência e Natura, vol. 45, art. no. e74574, 2023, doi: 10.5902/2179460X74574.

[20] C. E. Bahena-Méndez, J. M. Guevara-Vela, and T. Rocha-Rinza, "Aqueous microsolvation of bivalent Cu, Zn and Cd: Quantum chemical topology analyses of cooperativity, anticooperativity and covalency," J. Mol. Liq., vol. 397, art. no. 124068, 2024, doi: 10.1016/j.molliq.2024.124068.

[21] M. Mosaferi, D. Céolin, J.-P. Rueff, P. Selles, M. Odelius, O. Björneholm, et al., "Fingerprint of dipole moment orientation of water molecules in Cu²⁺ aqueous solution probed by X-ray photoelectron spectroscopy," J. Am. Chem. Soc., vol. 146, no. 14, pp. 9836–9850, 2024, doi: 10.1021/jacs.3c14570.

[22] Aydin, H. (2026). Machine Learning in Business Analytics: Evidence from US Industry Professionals. Journal of Computational Systems & Engineering Insights, 4(01), 36-47.

[23] E. G. Christensen, K. T. Lutz, R. J. Spencer, and R. P. Steele, "Persistence of a delocalized radical in larger clusters of hydrated copper(II) hydroxide, CuOH⁺(H₂O)₃₋₇," J. Phys. Chem. A, vol. 127, no. 32, pp. 6647–6659, 2023, doi: 10.1021/acs.jpca.3c03718.

[24] O. Y. Selyutina, P. A. Kononova, V. E. Koshman, L. G. Fedenok, and N. E. Polyakov, "The interplay of ascorbic acid with quinones-chelators—Influence on lipid peroxidation: Insight into anticancer activity," Antioxidants, vol. 11, no. 2, art. no. 376, 2022, doi: 10.3390/antiox11020376.

[25] A. Kola, G. Vigni, M. C. Baratto, and D. Valensin, "A combined NMR and UV–Vis approach to evaluate radical scavenging activity of rosmarinic acid and other polyphenols," Molecules, vol. 28, no. 18, art. no. 6629, 2023, doi: 10.3390/molecules28186629.

[26] B. Brooke, “Artificial intelligence and the emergence of autonomous enterprises: Implications for business model innovation and market dynamics,” Journal of Computational Systems & Engineering Insights, vol. 4, no. 1, pp. 26–35, 2026.

[27] J.-C. Lavoie and P. Chessex, "Parenteral nutrition and oxidant stress in the newborn: A narrative review," Free Radic. Biol. Med., vol. 142, pp. 155–167, 2019, doi: 10.1016/j.freeradbiomed.2019.02.020.

[28] H. Sun, G. Xie, D. He, and L. Zhang, "Ascorbic acid promoted magnetite Fenton degradation of alachlor: Mechanistic insights and kinetic modeling," Appl. Catal. B: Environ., vol. 267, art. no. 118383, 2020, doi: 10.1016/j.apcatb.2019.118383.

[29] O. Bellamy, “Leveraging entrepreneurial and intrapreneurial orientation to achieve operational excellence in aviation organizations,” International Journal of Business Integrity and Technology Advancements, vol. 2, no. 1, pp. 20–26, 2026.

[30] T. Moragues, M. Agrachev, S. Mitchell, G. Jeschke, J. Pérez-Ramírez, and A. J. deMello, "Droplet-based EPR spectroscopy for real-time monitoring of liquid-phase catalytic reactions," Small Methods, vol. 9, no. 7, 2025, doi: 10.1002/smtd.202401771.

[31] Y. Zhang, Q. Liu, Q. Lu, Z. Yang, S. Gao, and X. Zhang, "The preparation and dual-mode detection of ascorbic acid based on poly(N-isopropylacrylamide) nanogel with oxidase-like activity," Anal. Methods, vol. 16, no. 26, pp. 4255–4261, 2024, doi: 10.1039/D4AY00638K.

[32] E. M. Ellen, “AI-powered fraud detection: Integrating machine learning, natural language processing, and behavioral analytics for intelligent fraud prevention,” International Journal of Business Integrity and Technology Advancements, vol. 2, no. 2, pp. 1–7, 2026.

[33] Y. Yuan, J. Mi, and J. Shi, "Smartphone-integrated Ni-HHTP nanozyme sensor for colorimetric detection of ascorbic acid in fresh fruit juices," Phys. Scr., vol. 100, no. 12, art. no. 125011, 2025, doi: 10.1088/1402-4896/ae2549.

[34] L. Hou, Q. Li, J. Li, D. Yang, and Y. Yang, "Cu,Fe,B/Cur-CDs with peroxidase- and ascorbic acid oxidase-like catalytic activity for dual-signal fluorescence sensing of metronidazole," Food Chem., vol. 493, art. no. 145757, 2025, doi: 10.1016/j.foodchem.2025.145757.

[35] I. Alim, R. N. Meghla, T. F. Matin, and T. M. M. H. Prodhan, "A semantic and behavioral AI framework for detecting invoice fraud in automated accounts payable," *International Journal of Science and Research Archive*, vol. 19, no. 2, pp. 1356–1380, 2026.

[36] Martinello F, da Silva EL. Ascorbic acid interference in the measurement of serum biochemical parameters: in vivo and in vitro studies. Clinical biochemistry. 2006 Apr 1;39(4):396-403.

[37] M. Chaudhari, “R2R Plasma-Textured Polymer Films: Nanostructured AR/Hydrophobic Surfaces and EB Cured Varnish Proxies for Scalable Coatings,” Genetics and Molecular Research, vol. 25, no. 3, Art. no. 3018, Jul. 27, 2026. doi: 10.4238/e5d1rq05.

[38] Alkhadher SAA, Suratman S, Mohd Sallan MI. An evaluation of spatial and seasonal distributions of dissolved trace metals in the water of the natural wetlands. J Environ Manage. 2023;345:118464. doi:10.1016/j.jenvman.2023.118464

 [39] Bottoni C, Tegoni M, Borghesani V. Stability and pseudocatecholase activity of artificial bis-histidyl copper peptides. Inorg Chem. 2025;64(41):20567–76. doi:10.1021/acs.inorgchem.5c02080

[40] M. Chaudhari, “Hydrophilic Nanofiber Barrier Coatings for Aluminum: Waterborne Crosslinking, Microstructure–Property Links, and EIS-Based Protection,” Genetics and Molecular Research, vol. 25, no. 3, Art. no. 3017, Jul. 27, 2026. doi: 10.4238/rhd2k915.

[41] Anes B, Bettencourt da Silva RJN, Oliveira C, Camões MF. Seawater pH measurements with a combination glass electrode and high ionic strength TRIS-TRIS HCl reference buffers — an uncertainty evaluation approach. Talanta. 2019;193:118–22. doi:10.1016/j.talanta.2018.09.075

[42] M. A. Jawed, "Uncertainty-aware geostatistical reconstruction of regional groundwater hydraulics under sparse monitoring conditions: A case study of the Evergreen Underground Water Conservation District (EUWCD), Texas, USA," Bishop International Journal of Mathematics and Computer Science, vol. 1, no. 1, pp. 57–71, 2025.

[43] Zhao Y, Zhang H, Jin Q, Jia D, Liu T. Ratiometric optical fiber dissolved oxygen sensor based on fluorescence quenching principle. Sensors. 2022;22(13):4811. doi:10.3390/s22134811

[44] M. A. Jawed, "Comparative analysis of advanced oxidation processes (AOPs) vs. granular activated carbon (GAC) for PFAS removal in US groundwater suppliers: A techno-economic and life cycle assessment," International Journal of AI, Engineering and Management Studies (IJAIEMS), pp. 72–84, 2025.

[45] Balarak D, Mostafapour FK. Photocatalytic degradation of amoxicillin using UV/synthesized NiO from pharmaceutical wastewater. Indones J Chem. 2019;19(1):211–8. doi:10.22146/ijc.33837

[46] Hassan RM, Ibrahim SM, Khairou KS. Kinetics and mechanism of oxidation of pyruvate by permanganate ion in aqueous perchlorate solution. Transit Met Chem. 2018;43(8):683–91. doi:10.1007/s11243-018-0257-x

[47] Miller JN, Miller JC. Statistics and chemometrics for analytical chemistry. 7th ed. Harlow: Pearson Education; 2018.