Dissociation of magnesium oxide and magnesium hydroxide nanoparticles in physiologically relevant fluids

  • Cheyann Lee Wetteland
  • Jorge de Jesus Sanchez
  • Christine Allison Silken
  • Nhu-Y Thi Nguyen
  • Omar Mahmood
  • Huinan LiuEmail author
Research Paper


Magnesium oxide (MgO) and hydroxide [Mg(OH)2] are conventionally considered insoluble in water and stable at high temperatures. However, in this study, we found significant dissociation of MgO and Mg(OH)2 into ions when they were immersed in different physiologically relevant solutions in the form of 20-nm and 10-nm nanoparticles respectively, under standard cell culture conditions in vitro, i.e., a 37 °C, 5% CO2/95% air, sterile, humidified environment. The change in Mg2+ ion concentrations and pH measured in the physiologically relevant solutions (e.g., Dulbecco’s modified Eagle’s Medium (DMEM), simulated body fluid (SBF), relevant chloride solutions, and deionized water) confirmed their dissociation. Possible mechanisms and contributing factors for dissociation of MgO and Mg(OH)2 nanoparticles were discussed. The evidence suggests that nucleophilic substitution of OH by Cl in Mg(OH)2 is energetically unfavorable and it is more likely that Cl plays a role in the stabilization of intermediate forms of MgO and Mg(OH)2 as it dissociates. The pH and buffering capability of the immersion solutions might have played the most significant role in dissociation of these nanoparticles when compared with the roles of chloride (Cl), proteins, and different buffering agents. This article provided the first evidence on the dissociation of MgO and Mg(OH)2 nanoparticles in physiologically relevant conditions and elucidated possible factors contributing to the observed behaviors of these nanoparticles in vitro, which is important for their potential medical applications in vivo.

Graphical Abstract

Dissociation of magnesium oxide and magnesium hydroxide nanoparticles in physiologically relevant fluids


Magnesium oxide (MgO) nanoparticles Magnesium hydroxide [Mg(OH)2] nanoparticles Biofluids Dulbecco’s modified Eagle’s Medium (DMEM) Simulated body fluid (SBF) HEPES buffer Chloride (Cl) solutions 



The authors thank the Central Facility for Advanced Microscopy and Microanalysis (CFAMM) for the use of SEM FEI XL30 at the University of California at Riverside. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Funding information

The authors appreciate the financial support from the U.S. National Science Foundation (NSF award 1512764, 1125801, 1545852), the Burroughs Wellcome Fund (1011235), the Hellman Faculty Fellowship (HL), and the University of California (UC) Regents Faculty Development Award (HL).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Amundsen K et al. (2000) Magnesium. In: Ullmann’s Encyclopedia of Industrial Chemistry. Wiley-VCH Verlag GmbH & Co. KGaA., Magnesium
  2. Atkins PW (2010) Shriver & Atkins’ inorganic chemistry, 5th edn. Oxford University Press, OxfordGoogle Scholar
  3. Bhattachar SN, Deschenes LA, Wesley JA (2006) Solubility: it’s not just for physical chemists. Drug Discov Today 11:1012–1018. CrossRefGoogle Scholar
  4. Carpenter TO et al (2006) A randomized controlled study of effects of dietary magnesium oxide supplementation on bone mineral content in healthy girls. J Clin Endocrinol Metab 91:4866–4872. CrossRefGoogle Scholar
  5. Cipriano AF, Sallee A, Guan RG, Zhao ZY, Tayoba M, Sanchez J, Liu H (2015) Investigation of magnesium-zinc-calcium alloys and bone marrow derived mesenchymal stem cell response in direct culture. Acta Biomater 12:298–321. CrossRefGoogle Scholar
  6. Cipriano AF et al (2017a) Degradation of bioresorbable Mg-4Zn-1Sr intramedullary pins and associated biological responses in vitro and in vivo. ACS Appl Mater Interfaces 9:44332–44355. CrossRefGoogle Scholar
  7. Cipriano AF, Lin J, Miller C, Lin A, Cortez Alcaraz MC, Soria P Jr, Liu H (2017b) Anodization of magnesium for biomedical applications - processing, characterization, degradation and cytocompatibility. Acta Biomater 62:397–417. CrossRefGoogle Scholar
  8. Cotton FA, Wilkinson G (1988) Advanced inorganic chemistry, 5th edn. Wiley, New YorkGoogle Scholar
  9. Dean JA (1998) Lange’s handbook of chemistry, Fifteenth edn. McGraw-Hill, New YorkGoogle Scholar
  10. Dezfuli SN, Huan ZG, Mol JMC, Leeflang MA, Chang J, Zhou J (2014) Influence of HEPES buffer on the local pH and formation of surface layer during in vitro degradation tests of magnesium in DMEM. Prog Nat Sci-Mater 24:531–538. CrossRefGoogle Scholar
  11. Fedorockova A, Raschman P (2008) Effects of pH and acid anions on the dissolution kinetics of MgO. Chem Eng J 143:265–272. CrossRefGoogle Scholar
  12. Ferguson WJ et al (1980) Hydrogen-ion buffers for biological-research. Anal Biochem 104:300–310. CrossRefGoogle Scholar
  13. Fielding GA, Smoot W, Bose S (2014) Effects of SiO2, SrO, MgO, and ZnO dopants in tricalcium phosphates on osteoblastic Runx2 expression. J Biomed Mater Res A 102:2417–2426. CrossRefGoogle Scholar
  14. Fruhwirth O, Herzog GW, Hollerer I, Rachetti A (1985) Dissolution and hydration kinetics of Mgo, Surf Technol. 24:301–317.
  15. Gstraunthaler G, Toni L (2013) Zell-und Gewebekultur, 7th edn. Springer Spektrum, Berlin, HeidelbergGoogle Scholar
  16. Iskandar ME, Aslani A, Liu H (2013) The effects of nanostructured hydroxyapatite coating on the biodegradation and cytocompatibility of magnesium implants. J Biomed Mater Res A 101:2340–2354. CrossRefGoogle Scholar
  17. Ito T, Kato M, Toi K, Shirakawa T, Ikemoto I, Tokuda T (1985) Oxygen species adsorbed on ultraviolet-irradiated magnesium-oxide. J Chem Soc Farad T 81:2835–2844.
  18. Jadhav SA (2014) Interesting nanoshapes by “nano artwork”. Adv Mater Lett 5(10):557–561.
  19. Johnson I, Liu H (2013) A study on factors affecting the degradation of magnesium and a magnesium-yttrium alloy for biomedical applications. PLoS One 8:e65603. CrossRefGoogle Scholar
  20. Kokubo T, Kushitani H, Sakka S, Kitsugi T, Yamamuro T (1990) Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. J Biomed Mater Res 24:721–734. CrossRefGoogle Scholar
  21. Kroll MH, Elin RJ (1985) Relationships between magnesium and protein concentrations in serum. Clin Chem 31:244–246Google Scholar
  22. Kum CH, Cho Y, Seo SH, Joung YK, Ahn DJ, Han DK (2014) A poly(lactide) stereocomplex structure with modified magnesium oxide and its effects in enhancing the mechanical properties and suppressing inflammation. Small 10:3783–3794. CrossRefGoogle Scholar
  23. Láska M, Valtýni J, Fellner P (1993) Influence of pH on the crystal size distribution of Mg(OH)2 prepared by the hydration of MgO crystal research and technology. Cryst Res Technol 28(7):931–936Google Scholar
  24. Li C, Zhuang Z, Huang F, Wu Z, Hong Y, Lin Z (2013) Recycling rare earth elements from industrial wastewater with flowerlike nano-Mg(OH)(2) ACS. Appl Mater Interfaces 5:9719–9725. CrossRefGoogle Scholar
  25. Liu H (2011) The effects of surface and biomolecules on magnesium degradation and mesenchymal stem cell adhesion. J Biomed Mater Res A 99:249–260. CrossRefGoogle Scholar
  26. Lock JY, Wyatt E, Upadhyayula S, Whall A, Nunez V, Vullev VI, Liu H (2014) Degradation and antibacterial properties of magnesium alloys in artificial urine for potential resorbable ureteral stent applications. J Biomed Mater Res A 102:781–792. CrossRefGoogle Scholar
  27. Mejias JA, Berry AJ, Refson K, Fraser DG (1999) The kinetics and mechanism of MgO dissolution. Chem Phys Lett 314:558–563. CrossRefGoogle Scholar
  28. Mueller WD, de Mele MF, Nascimento ML, Zeddies M (2009) Degradation of magnesium and its alloys: dependence on the composition of the synthetic biological media. J Biomed Mater Res A 90:487–495. CrossRefGoogle Scholar
  29. Oyane A, Kim HM, Furuya T, Kokubo T, Miyazaki T, Nakamura T (2003) Preparation and assessment of revised simulated body fluids. J Biomed Mater Res A 65:188–195. CrossRefGoogle Scholar
  30. Patel MK et al (2013) Biocompatible nanostructured magnesium oxide-chitosan platform for genosensing application. Biosens Bioelectron 45:181–188. CrossRefGoogle Scholar
  31. Peng QM, Guo JX, Fu H, Cai XC, Wang YN, Liu BZ, Xu ZG (2014) Degradation behavior of Mg-based biomaterials containing different long-period stacking ordered phases. Scientific Reports 4:ARTN 3620. CrossRefGoogle Scholar
  32. Pourdanesh F, Jebali A, Hekmatimoghaddam S, Allaveisie A (2014) In vitro and in vivo evaluation of a new nanocomposite, containing high density polyethylene, tricalcium phosphate, hydroxyapatite, and magnesium oxide nanoparticles. Mater Sci Eng C Mater Biol Appl 40:382–388. CrossRefGoogle Scholar
  33. Press C (2017) CRC handbook of chemistry and physics, 98th edn. CRC Press : Taylor & Francis, Boca RatonGoogle Scholar
  34. Refson K, Wogelius RA, Fraser DG, Payne MC, Lee MH, Milman VV (1995) Water chemisorption and reconstruction of the MgO surface. Phys Rev B Condens Matter 52:10823–10826CrossRefGoogle Scholar
  35. Sawai J (2003) Quantitative evaluation of antibacterial activities of metallic oxide powders (ZnO, MgO and CaO) by conductimetric assay. J Microbiol Methods 54:177–182CrossRefGoogle Scholar
  36. Sawai J, Yoshikawa T (2004) Quantitative evaluation of antifungal activity of metallic oxide powders (MgO, CaO and ZnO) by an indirect conductimetric assay. J Appl Microbiol 96:803–809CrossRefGoogle Scholar
  37. Stellwagen E, Prantner JD, Stellwagen NC (2008) Do zwitterions contribute to the ionic strength of a solution? Anal Biochem 373:407–409. CrossRefGoogle Scholar
  38. Stendig-Lindberg G, Tepper R, Leichter I (1993) Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res 6:155–163Google Scholar
  39. Tie D et al (2016) An in vivo study on the metabolism and osteogenic activity of bioabsorbable Mg–1Sr alloy. Acta Biomaterialia 29:455–467. CrossRefGoogle Scholar
  40. Wetteland CL, Nguyen NY, Liu H (2016) Concentration-dependent behaviors of bone marrow derived mesenchymal stem cells and infectious bacteria toward magnesium oxide nanoparticles. Acta Biomater 35:341–356. CrossRefGoogle Scholar
  41. Wolthuis E, Pruiksma AB, Heerema RP (1960) Determination of solubility: a laboratory experiment. J Chem Educ 37:137–138CrossRefGoogle Scholar
  42. Yanagisawa Y (1981) Interaction of oxygen molecules with surface centers of UV-irradiated MgO. J Phys Soc Japan 50:209–216CrossRefGoogle Scholar
  43. Yoshizawa S, Brown A, Barchowsky A, Sfeir C (2014a) Magnesium ion stimulation of bone marrow stromal cells enhances osteogenic activity, simulating the effect of magnesium alloy degradation. Acta Biomater 10:2834–2842. CrossRefGoogle Scholar
  44. Yoshizawa S, Brown A, Barchowsky A, Sfeir C (2014b) Role of magnesium ions on osteogenic response in bone marrow stromal cells. Connect Tissue Res 55(Suppl 1):155–159. CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of BioengineeringUniversity of CaliforniaRiversideUSA
  2. 2.Microbiology ProgramUniversity of CaliforniaRiversideUSA
  3. 3.Materials Science and Engineering ProgramUniversity of CaliforniaRiversideUSA

Personalised recommendations