Abstract
A novel strategy for designing highly efficient and activatable photosensitizers that can effectively generate reactive oxygen species (ROS) under both normoxia and hypoxia is proposed. Replacing both oxygen atoms in conventional naphthalimides (RNI-O) with sulfur atoms led to dramatic changes in the photophysical properties. The remarkable fluorescence quenching (φPL ≈ 0) of the resulting thionaphthalimides (RNI-S) suggested that the intersystem crossing from the singlet excited state to the reactive triplet state was enhanced by the sulfur substitution. Surprisingly, the singlet oxygen quantum yield of RNI-S gradually increased with increasing electron-donating ability of the 4-R substituents (MANI-S, φΔ ≈ 1.00, in air-saturated acetonitrile). Theoretical studies revealed that small singlet-triplet energy gaps and large spin-orbit coupling could be responsible for the efficient population of the triplet state of RNI-S. In particular, the ROS generation ability of MANI-S was suppressed under physiological conditions due to their self-assembly and was significantly recovered in cancer cells. More importantly, cellular experiments showed that MANI-S still produced a considerable amount of ROS even under severely hypoxic conditions (1% O2) through a type-I mechanism.
| Original language | English |
|---|---|
| Pages (from-to) | 16243-16248 |
| Number of pages | 6 |
| Journal | Journal of the American Chemical Society |
| Volume | 141 |
| Issue number | 41 |
| DOIs | |
| Publication status | Published - 2019 Oct 16 |
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ASJC Scopus subject areas
- Catalysis
- Chemistry(all)
- Biochemistry
- Colloid and Surface Chemistry
Cite this
An Emerging Molecular Design Approach to Heavy-Atom-Free Photosensitizers for Enhanced Photodynamic Therapy under Hypoxia. / Nguyen, Van Nghia; Qi, Sujie; Kim, Sangin; Kwon, Nahyun; Kim, Gyoungmi; Yim, Yubin; Park, Sungnam; Yoon, Juyoung.
In: Journal of the American Chemical Society, Vol. 141, No. 41, 16.10.2019, p. 16243-16248.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An Emerging Molecular Design Approach to Heavy-Atom-Free Photosensitizers for Enhanced Photodynamic Therapy under Hypoxia
AU - Nguyen, Van Nghia
AU - Qi, Sujie
AU - Kim, Sangin
AU - Kwon, Nahyun
AU - Kim, Gyoungmi
AU - Yim, Yubin
AU - Park, Sungnam
AU - Yoon, Juyoung
PY - 2019/10/16
Y1 - 2019/10/16
N2 - A novel strategy for designing highly efficient and activatable photosensitizers that can effectively generate reactive oxygen species (ROS) under both normoxia and hypoxia is proposed. Replacing both oxygen atoms in conventional naphthalimides (RNI-O) with sulfur atoms led to dramatic changes in the photophysical properties. The remarkable fluorescence quenching (φPL ≈ 0) of the resulting thionaphthalimides (RNI-S) suggested that the intersystem crossing from the singlet excited state to the reactive triplet state was enhanced by the sulfur substitution. Surprisingly, the singlet oxygen quantum yield of RNI-S gradually increased with increasing electron-donating ability of the 4-R substituents (MANI-S, φΔ ≈ 1.00, in air-saturated acetonitrile). Theoretical studies revealed that small singlet-triplet energy gaps and large spin-orbit coupling could be responsible for the efficient population of the triplet state of RNI-S. In particular, the ROS generation ability of MANI-S was suppressed under physiological conditions due to their self-assembly and was significantly recovered in cancer cells. More importantly, cellular experiments showed that MANI-S still produced a considerable amount of ROS even under severely hypoxic conditions (1% O2) through a type-I mechanism.
AB - A novel strategy for designing highly efficient and activatable photosensitizers that can effectively generate reactive oxygen species (ROS) under both normoxia and hypoxia is proposed. Replacing both oxygen atoms in conventional naphthalimides (RNI-O) with sulfur atoms led to dramatic changes in the photophysical properties. The remarkable fluorescence quenching (φPL ≈ 0) of the resulting thionaphthalimides (RNI-S) suggested that the intersystem crossing from the singlet excited state to the reactive triplet state was enhanced by the sulfur substitution. Surprisingly, the singlet oxygen quantum yield of RNI-S gradually increased with increasing electron-donating ability of the 4-R substituents (MANI-S, φΔ ≈ 1.00, in air-saturated acetonitrile). Theoretical studies revealed that small singlet-triplet energy gaps and large spin-orbit coupling could be responsible for the efficient population of the triplet state of RNI-S. In particular, the ROS generation ability of MANI-S was suppressed under physiological conditions due to their self-assembly and was significantly recovered in cancer cells. More importantly, cellular experiments showed that MANI-S still produced a considerable amount of ROS even under severely hypoxic conditions (1% O2) through a type-I mechanism.
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UR - http://www.scopus.com/inward/citedby.url?scp=85073247516&partnerID=8YFLogxK
U2 - 10.1021/jacs.9b09220
DO - 10.1021/jacs.9b09220
M3 - Article
C2 - 31577431
AN - SCOPUS:85073247516
VL - 141
SP - 16243
EP - 16248
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 41
ER -