Overview of experimental and computational methods for the determination of the pKa values of 5-fluorouracil, cyclophosphamide, ifosfamide, imatinib and methotrexate

Katarzyna Mioduszewska , Joanna Dołżonek , Dariusz Wyrzykowski , Łukasz Kubik , Paweł Wiczling , Celina Sikorska , Michał Toński , Zbigniew Kaczyński , Piotr Stepnowski , Anna Białk-Bielińska


We present a review of the available literature concerning pKa values and methods for the determination of selected anticancer drugs as well as the most up-to-date knowledge on their different ionic forms depending on solution pH. Additionally, to clarify the existing state of knowledge we have presented an overview on the obtained pKa values with the use of experimental and computational methods. As a result, we have demonstrated and proposed acid-base equilibria of cyclophosphamide (CF), ifosfamide (IF), 5-fluorouracil (5-FU), methotrexate (MTX), and imatinib (IMT) in an aqueous solution, and their species distribution curves as a function of pH calculated on the basis of the acid dissociation constants, which are as follows:CF pKa1 2.3, pKa2 11.1 [CF-H2L+/CF-HL/CF-L−]IF pKa1 < 2.5, pKa2 9.1 [IF-H2L+/IF-HL/IF-L−]5-FU pKa1 7.5, pKa2 9.0 [5-FU-H2L/5-FU-HL−/5-FU-L2−]MTX pKa1 2.9, pKa2 4.6, pKa3 6.6 [MTX-H3L+/MTX-H2L/MTX-HL−/MTX-L2−]IMT pKa1 2.5, pKa2 4.0, pKa3 8.3 [IMT-H3L3+/IMT-H2L2+/IMT-HL+/MTX-L].
Author Katarzyna Mioduszewska PChZŚ
Katarzyna Mioduszewska,,
- Laboratory of Chemical Environmental Risks
, Joanna Dołżonek PChZŚ
Joanna Dołżonek,,
- Laboratory of Chemical Environmental Risks
, Dariusz Wyrzykowski PBChN
Dariusz Wyrzykowski,,
- Pracownia Biologicznej Chemii Nieorganicznej
, Łukasz Kubik
Łukasz Kubik,,
, Paweł Wiczling
Paweł Wiczling,,
, Celina Sikorska PMM
Celina Sikorska,,
- Laboratory of Molecular Modeling
, Michał Toński PChZŚ
Michał Toński,,
- Laboratory of Chemical Environmental Risks
, Zbigniew Kaczyński PBS
Zbigniew Kaczyński,,
- Laboratory of Structural Biochemistry
, Piotr Stepnowski PChZŚ
Piotr Stepnowski,,
- Laboratory of Chemical Environmental Risks
, Anna Białk-Bielińska PChZŚ
Anna Białk-Bielińska,,
- Laboratory of Chemical Environmental Risks
Journal seriesTrac-Trends in Analytical Chemistry, ISSN 0165-9936
Issue year2017
Publication size in sheets0.65
Keywords in Englishdissociation constant, anticancer drugs, acid-base equilibrium, experimental and computational methods, cytostatic drugs
URL https://doi.org/10.1016/j.trac.2017.09.009
Languageen angielski
Score (nominal)50
ScoreMinisterial score = 50.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 50.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 8.442 (2) - 2016=7.929 (5)
Citation count*0
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.