Enhanced Drug Photosafety by Interchromophoric Interaction Owing to Intramolecular Charge Separation

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 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.

Characterization of Locally Excited and Charge‐Transfer States of the Anticancer Drug Lapatinib by Ultrafast Spectroscopy and Computational Studies

“…However, the fluorescence was dramatically enhanced in a solid ethanol matrix at 77 K (see Figures S1 and S2 in the Supporting Information). This effect can be attributed to the restriction in the degrees of freedom for conformational relaxation in the frozen medium, which could prevent a possible intramolecular charge‐transfer (ICT), similar to that previously observed for related drugs [10] …”

“…This effect can be attributed to the restriction in the degrees of freedom for conformational relaxation in the frozen medium, which could prevent ap ossible intramolecular charge-transfer (ICT), similartot hat previously observed for related drugs. [10] The photobehavioro fL AP was also investigated in aqueous mediuma nd in the presence of human serum albumin( HSA). In PBS LAP is known to form aggregates; [9c] this is clearly shown by the UV absorption spectra (see Figure S3 in the Supporting Information).…”

Time-Resolved Spectroscopic and Density Functional Theory Investigation of the Photogeneration of a Bifunctional Quinone Methide in Neutral and Basic Aqueous Solutions

“…Time-dependent DFT (TD-DFT) calculations have been previously illustrated to be helpful in evaluating and identifying the absorption features of intermediate species [23,24]. Based on the spectral data, a simple mechanism can be deduced that the NMe 3 group in QMP-b leaves in a process to form the QM species due to an E1cb elimination reaction [25,26].…”

Preise der Spanischen Chemischen Gesellschaft 2018

“…Miranda forscht auf dem Gebiet der Photochemie, insbesondere über die Mechanismen organischer Photoreaktionen, supramolekulare Photochemie mit Biomolekülen und photobiologische Anwendungen. In Chemistry—A European Journal berichtete er über einen synthetischen Tyrosinasehemmer …”