Skip to main content
SpringerLink
Log in

Surfactant-free air bubble flotation–coagulation for the rapid purification of chloroquine

  • Original Paper
  • Published:
Analytical Sciences Aims and scope Submit manuscript

Abstract

A simple and rapid separation method based on surfactant-free air bubble flotation and coagulation was designed for the purification of chloroquine (CQ) from its crude product. An open glass column having a sintered glass filter (for column chromatography) was used as a flotation vessel. The flotation was conducted by pouring the crude CQ into the aqueous solution containing 0.1% (v/v) of 2-propanol followed by feeding air through the glass filter to generate air bubbles. At pH 12, CQ was enriched into the foam temporary generating on the surface of water to form the coagulates within 90 s after the start of the air bubble flotation. On the other hand, reactants; 4,7-dichloroquinoline and 4-amino-1-diethylaminopentane, as well as generated impurities remained in the bulk aqueous solution. The result of dynamic surface tension measurement indicated that CQ molecules selectively adsorbed on the air–water interface and the coagulates more strongly adsorbed the interface. Adsorption and coagulation of CQ molecules on the air–water interface were also reproduced in the calculation results of a molecular dynamic simulation. The coagulates were collected from the surface of water by suction and then poured into another flotation vessel for conducting repeated separation. The time required for the respective separation process including air bubble flotation and collection by suction was within 5 min. After three-times separation, highly purified (> 99.0%) CQ was obtained with a yield of 72 ± 8%. The amounts of reactants and other impurities reduced into undetectable levels.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. R. Thomé, S.C.P. Lopes, F.T.M. Costa, L. Verinaud, L. Verinaud, Chloroquine: modes of action of an undervalued drug. Immunol. Lett. 153, 50–57 (2013). https://doi.org/10.1016/j.imlet.2013.07.004

    Article  CAS  Google Scholar 

  2. WHO. World malaria report 2020: 20 years of global progress and challenges (World Health Organization, Geneva, 2020). https://www.who.int/publications/i/item/9789240015791

  3. A. Savarino, L.D. Trani, I. Donatelli, R. Cauda, A. Cassone, New insights into the antiviral effects of chloroquine. Lancet. Infect. Dis. 6, 67–69 (2006). https://doi.org/10.1016/S1473-3099(06)70361-9

    Article  Google Scholar 

  4. P. Maycotte, S. Aryal, C.T. Cummings, J. Thorburn, Chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy. Autophagy 8, 200–211 (2012). https://doi.org/10.4161/auto.8.2.18554

    Article  CAS  Google Scholar 

  5. M.A.A. Al-Bari, Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol. Res. Perspect. 5, e00293 (2017). https://doi.org/10.1002/prp2.293

    Article  CAS  Google Scholar 

  6. Y.W. Tan, W.K. Yam, J. Sun, J.J.H. Chu, An evaluation of chloroquine as a broad-acting antiviral against hand, foot and mouth disease. Antiviral Res. 149, 143–149 (2018). https://doi.org/10.1016/j.antiviral.2017.11.017

    Article  CAS  Google Scholar 

  7. D. Plantone, T. Koudriavtseva, Current and future use of chloroquine and hydroxychloroquine in infectious, immune, neoplastic, and neurological diseases: a mini-review. Clin. Drug Investig. 38, 653–671 (2018). https://doi.org/10.1007/s40261-018-0656-y

    Article  CAS  Google Scholar 

  8. A.W. Zhou, H. Wang, Y. Yang, Z.S. Chen, C. Zou, Chloroquine against malaria, cancers and viral diseases. Drug Discovery Today 25, 2012–2022 (2020). https://doi.org/10.1016/j.drudis.2020.09.010

    Article  CAS  Google Scholar 

  9. W.S. Johnson, B.G. Buell, A new synthesis of chloroquine. J. Am. Chem. Soc. 74, 4513–4516 (1952). https://doi.org/10.1021/ja01138a014

    Article  CAS  Google Scholar 

  10. F.A.R. Ruiz, R.N. García-Sánchez, S.V. Estupiñan, A. Gómez-Barrio, D.F.T. Amado, B.M. Pérez-Solórzano, J.J. Nogal-Ruiz, A.R. Martínez-Fernández, V.V. Kouznetsov, Synthesis and antimalarial activity of new heterocyclic hybrids based on chloroquine and thiazolidinone scaffolds. Bioorg. Med. Chem. 19, 4562–4563 (2011). https://doi.org/10.1016/j.bmc.2011.06.025

    Article  CAS  Google Scholar 

  11. K. Kodama, M. Oiwa, T. Saitoh, Purification of Rhodamine B by alcohol-modified air bubble flotation. Bull. Chem. Soc. Jpn. 94, 1210–1214 (2021). https://doi.org/10.1246/bcsj.20200395

    Article  CAS  Google Scholar 

  12. C. Rendal, K.O. Kusk, S. Trapp, The effect of pH on the uptake and toxicity of the bivalent weak base chloroquine tested on Salix viminalis and Daphnia magna. Environ. Toxicol. Chem. 30, 324–359 (2011). https://doi.org/10.1002/etc.391

    Article  CAS  Google Scholar 

  13. A. Breindl, B. Beck, T. Clark, Prediction of the n-octanol/water partition coefficient, log P, Using a combination of semiempirical MO-calculations and a neural network. J. Mol. Model. 3, 142–155 (1997). https://doi.org/10.1007/s008940050027

    Article  CAS  Google Scholar 

  14. M. Mucha, B. Minofar, P. Jungwirth, E.C. Brown, D.J. Tobias, Propensity of soft ions for the air/water interface. Curr. Op. Colloid In. 9, 67–73 (2004). https://doi.org/10.1016/j.cocis.2004.05.02

    Article  Google Scholar 

  15. P. Jungwirth, D.J. Tobias, Specific ion effects at the air/water interface. Chem. Rev. 106, 1259–1281 (2006). https://doi.org/10.1021/cr0403741

    Article  CAS  Google Scholar 

  16. Y.L.S. Tse, C. Chen, G.E. Lindberg, R. Kumar, G.A. Voth, Propensity of hydrated excess protons and hydroxide anions for the air-water interface. J. Am. Chem. Soc. 137, 12610–12616 (2015). https://doi.org/10.1021/jacs.5b07232

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a Grant-in-Aid for Challenging Research (Pioneering) (21K19319) and a Grant-in-Aid for Scientific Research (B) (22H02115).

Author information

Authors and Affiliations

  1. Graduate School of Engineering, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido, 090-8507, Japan

    Koki Kodama & Tohru Saitoh

Authors
  1. Koki Kodama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tohru Saitoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tohru Saitoh.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kodama, K., Saitoh, T. Surfactant-free air bubble flotation–coagulation for the rapid purification of chloroquine. ANAL. SCI. 39, 43–49 (2023). https://doi.org/10.1007/s44211-022-00196-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s44211-022-00196-2

Keywords

Search

Navigation