Protonation of Tyrosine Kinase Inhibitor Lapatinib: A Theoretical and Experimental Study

Abstract:

The protonation process of tyrosine kinase inhibitor lapatinib was studied by means of ¹HNMR 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 of 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.

• Periodical: Key Engineering Materials (Volume 800)
• Pages: 19-24
• DOI: https://doi.org/10.4028/www.scientific.net/KEM.800.19
• Online since: April 2019
• Authors: Ilze Grante*, Rihards Klūga, Liāna Orola
• Keywords: Lapatinib, NMR Spectroscopy, Protonation, UV/Vis Spectroscopy, ZINDO/S

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