Protonation of tyrosine kinase inhibitor lapatinib: A theoretical and experimental study

Ilze Grante, Rihards Kluga, Liana Orola

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review


The protonation process of tyrosine kinase inhibitor lapatinib was studied by means of 1H NMR and UV/Vis spectroscopy joint with the theoretical calculations at DFT and semi-empirical levels. DFT/M06-2X geometries were used to describe and compare the different cationic forms of lapatinib, while ZINDO/S-CI method performed on those geometries allowed for the interpretation by experimental UV/Vis spectra of lapatinib at various pH. We found that at low pH two different dicationic forms (N2N1 and N1N3) of lapatinib were present in ethanol and DMSO-d6 solutions. The first protonation, however, occurred on the aliphatic N1 in DMSO-d6, while in ethanol solutions most probably the quinazoline nitrogen atom N2 was also protonated.

Publication series

NameKey Engineering Materials
Volume800 KEM
ISSN (Print)1013-9826
ISSN (Electronic)1662-9795


Conference59th International Scientific Conference of Riga Technical University (RTU)
Abbreviated titleMSAC 2018
Internet address


  • Lapatinib
  • NMR spectroscopy
  • Protonation
  • UV/Vis spectroscopy

Field of Science*

  • 3.1 Basic medicine
  • 1.4 Chemical sciences

Publication Type*

  • 3.1. Articles or chapters in proceedings/scientific books indexed in Web of Science and/or Scopus database


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