Enhanced Drug Photosafety by Interchromophoric Interaction Owing to Intramolecular Charge Separation. Issue 25 (10th April 2018)

• Record Type: Journal Article
• Authors: Li, Ming‐De; Yan, Zhiping; Zhu, Ruixue; Phillips, David Lee; Aparici‐Espert, Isabel; Lhiaubet‐Vallet, Virginie; Miranda, Miguel A.
• Is Part Of: Chemistry. Volume 24:Issue 25(2018)
• Page Start: 6654
• Page End: 6659
• Publication Date: 2018-04-10
• Subjects: absorption -- charge separation -- chromophores -- electronic structure -- raman spectroscopy; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201800716
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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 compound1 and diaminotoluene. In contrast, compound1 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. Abstract : An intramolecular charge separation is directly observed by ultrafast laser spectroscopy measurements in Imatinib, a synthetic kinase inhibitor, through interchromophoric interaction, which significantly increases the photostability of Imatinib and enhances its drug photosafety (see picture). This can help guide strategies for the design of new nonphototoxic drugs.