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Enhanced Drug Photosafety by Interchromophoric Interaction Owing to Intramolecular Charge Separation
Author(s) -
Li MingDe,
Yan Zhiping,
Zhu Ruixue,
Phillips David Lee,
ApariciEspert Isabel,
LhiaubetVallet Virginie,
Miranda Miguel A.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800716
Subject(s) - chemistry , excited state , intramolecular force , photochemistry , phototoxicity , hela , stereochemistry , atomic physics , biochemistry , physics , in vitro , cell
Imatinib is a synthetic tyrosinase inhibitor that is employed for the treatment of some kinds of human cancer. This drug has a low phototoxicity towards DNA, but its pyridylpyrimidine ( 1 ) fragment by itself exhibits significant phototoxicitiy. The intrinsic mechanism that leads to the enhanced photosafety of Imatinib is not yet known. Here, the properties of the excited state and interchromophoric interactions of Imatinib have been explored by using ultrafast laser flash photolysis and agarose electrophoresis studies. An intramolecular charge separation was directly observed for the irradiated Imatinib, which accounts for the relaxation of its excited state. An anionic form of pyridylpyrimidine ( 1 ) was deduced from the results of time‐resolved resonance Raman spectra and by quenching experimental studies on compound 1 and diaminotoluene. In contrast, compound 1 efficiently transformed into triplet excited states with a long lifetime, which explained the phototoxicity associated with this fragment. This work provides insight into how to design drugs with lower phototoxicitiy or improved photostability by using interchromophoric interactions.