Time-Dependent Density Functional Theoretical Investigation of Photoinduced Excited-State Intramolecular Dual Proton Transfer in Diformyl Dipyrromethanes

In recent research [Chem. Commun. 2014, 50, 8667], it was found that photoinduced enolization occurred in 1,9-diformyl-5,5-diaryldipyrromethane (DA_KK) by excited-state dual proton transfer resulting in a red-shifted absorption, a phenomena not observed in 1,9-diformyl-5,5-dimethyldipyrromethane (DM_KK) and 1,9-diformyl-5-aryldipyrromethane (MA_KK). The observation was supported by preliminary density functional theoretical (DFT) calculations. In the work reported here, a detailed and systematic study was undertaken considering four molecules, 1,9-diformyldipyrromethane (DH_KK), DM_KK, MA_KK, and DA_KK and their rotational isomers using DFT methods. Different processes, namely, cis–trans isomerization and single and double proton transfer processes, and their mechanistic details were investigated in the ground and excited states. From the simulation studies, it was seen that the presence of different substituents at the meso carbon does not affect the λ_abs values during cis → trans isomerization. However, enolization by proton transfer processes were found to be influenced by the substituents, as seen in the experiments. Enolization was observed to follow a stepwise mechanism, that is, diketo → monoenol → dienol. While monoenols showed negligible substituent effects on the λ_abs values, a large red shift in λ_abs was seen only in DA_KK, in agreement with the experimental findings. This observation can be attributed to the lowering of the keto → enol activation barrier, stabilization of DA_EE in the S₁ state, and the charge transfer nature of the transitions involved in DA_EE

<i>In Vitro</i> Demonstration of Apoptosis Mediated Photodynamic Activity and NIR Nucleus Imaging through a Novel Porphyrin

We synthesized a novel water-soluble porphyrin <b>THPP</b> and its metalated derivative <b>Zn-THPP</b> having excellent triplet excited state quantum yields and singlet oxygen generation efficiency. When compared to U.S. Food and Drug Administration approved and clinically used sensitizer Photofrin, <b>THPP</b> showed <i>ca.</i> 2–3-fold higher <i>in vitro</i> photodynamic activity in different cell lines under identical conditions. The mechanism of the biological activity of these porphyrin systems has been evaluated through a variety of techniques: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, comet assay, poly­(ADP-ribose)­polymerase (PARP) cleavage, CM-H₂DCFDA assay, DNA fragmentation, flow cytometric analysis, fluorescence, and confocal microscopy, which confirm the apoptotic cell death through predominantly reactive oxygen species (ROS). Moreover, <b>THPP</b> showed rapid cellular uptake and are localized in the nucleus of the cells as compared to Hoechst dye and Photofrin, thereby demonstrating its use as an efficient sensitizer in photodynamic therapy and live cell NIR nucleus imaging applications