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Published on: August 30, 2017
Molecular Design of Highly Efficient Heavy-Atom-free NpImidazole Derivatives for Two-Photon Photodynamic Therapy and
Wei-Bo Cui1, Xue Wei1, Jing-Fu Guo2
1Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Liutiao Road #2, Changchun 130061, P. R. China.
Abstract:
Two-photon photodynamic therapy (TP-PDT), as a treatment technology with deep penetration and less damage, provides a broad prospect for cancer treatment. Nowadays, the development of TP-PDT suffers from the low two-photon absorption (TPA) intensity and short triplet state lifetime of photosensitizers (PSs) used in TP-PDT. Herein, we propose some novel modification strategies based on the thionated NpImidazole (the combination of naphthalimide and imidazole) derivatives to make efforts on those issues and obtain corresponding fluorescent probes for detecting ClO- and excellent PSs for TP-PDT. Density functional theory (DFT) and time-dependent DFT (TD-DFT) are used to help us characterize the photophysical properties and TP-PDT process of the newly designed compounds. Our results show that the introduction of different electron-donating groups at the position 4 of NpImidazole can effectively improve their TPA and emission properties. Specifically, 3s with a N,N-dimethylamino group has a large triplet state lifetime (τ = 699 μs) and TPA cross section value (δTPA = 314 GM), which can effectively achieve TP-PDT; additionally, 4s (with electron-donating group 2-oxa-6-azaspiro[3.3]heptane in NpImidazole) effectively realizes the dual-function of a PS for TP-PDT (τ = 25,122 μs, δTPA = 351 GM) and a fluorescent probe for detecting ClO- (Φf = 29% of the product 4o). Moreover, an important problem is clarified from a microscopic perspective, that is, why the transition property of 3s and 4s (1π-π*) from S1 to S0 is different from that of 1s and 2s (1n-π*). It is hoped that our work can provides valuable theoretical clues for the design and synthesis of heavy-atom-free NpImidazole-based PSs and fluorescent probes for the detection of hypochlorite.
Insights
Novel thionated NpImidazole derivatives show improved two-photon absorption (TPA) and triplet state lifetimes, enhancing their potential as photosensitizers (PSs) for two-photon photodynamic therapy (TP-PDT) and fluorescent probes.
Area of Science:
- Organic Chemistry
- Photochemistry
- Computational Chemistry
Background:
- Two-photon photodynamic therapy (TP-PDT) offers deep tissue penetration and reduced damage for cancer treatment.
- Current photosensitizers (PSs) for TP-PDT often exhibit low two-photon absorption (TPA) intensity and short triplet state lifetimes.
- Developing effective PSs and fluorescent probes remains a challenge.
Purpose of the Study:
- To design and theoretically investigate novel thionated NpImidazole derivatives as potential PSs for TP-PDT and fluorescent probes.
- To address limitations in TPA intensity and triplet state lifetime of existing PSs.
- To explore structure-property relationships for optimized TP-PDT and ClO- detection.
Main Methods:
- Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) calculations were employed.
- Photophysical properties, including TPA cross-sections and triplet state lifetimes, were characterized.
- Theoretical analysis of electronic transitions and structure-property relationships was performed.
Main Results:
- Introduction of electron-donating groups at position 4 of NpImidazole significantly enhanced TPA and emission properties.
- Compound 3s demonstrated a substantial triplet state lifetime (699 μs) and TPA cross-section (314 GM), suitable for TP-PDT.
- Compound 4s exhibited dual functionality as a TP-PDT agent (25,122 μs lifetime, 351 GM TPA) and a fluorescent probe for ClO- detection (29% quantum yield).
- Microscopic insights into the differing transition properties (1π-π* vs. 1n-π*) of the designed compounds were elucidated.
Conclusions:
- The designed thionated NpImidazole derivatives show promise as efficient PSs for TP-PDT and fluorescent probes.
- Strategic modification with electron-donating groups is effective in optimizing photophysical properties.
- This work provides valuable theoretical guidance for developing heavy-atom-free NpImidazole-based agents for TP-PDT and hypochlorite detection.
