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
AbstractWe 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].
|Journal series||Trac-Trends in Analytical Chemistry, ISSN 0165-9936, (A 50 pkt)|
|Publication size in sheets||0.65|
|Keywords in English||dissociation constant, anticancer drugs, acid-base equilibrium, experimental and computational methods, cytostatic drugs|
|Score||= 50.0, 29-05-2020, ArticleFromJournal|
|Publication indicators||= 14; = 11; : 2017 = 2.004; : 2017 = 7.034 (2) - 2017=7.621 (5)|
|Citation count*||16 (2020-05-21)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.