Probe‐Free Direct Identification of Type I and Type II Photosensitized Oxidation Using Field‐Induced Droplet Ionization Mass Spectrometry

Abstract

While Type I and Type II photosensitizers are often carefully tailored to achieve their respective advantages in treating different cancers, the identifications of the Type I and II mechanisms as such, the key reaction intermediates, and the consequent oxidation products of the substrates have never been easy. Using our unique home‐built field‐induced droplet ionization mass spectrometry (FIDI‐MS) method that selectively samples molecules at the air–water interface, here we show the facile determination of both Type I and II mechanisms of a poster‐child photosensitizer, temoporfin, without the addition of any probes. The unstable doublet radical resulting from the hydrogen abstraction by the triplet temoporfin through the Type I mechanism is captured, manifesting the in situ advantage of FIDI‐MS. We anticipate that the method developed in this study can be widely utilized in the future designs of novel photosensitizers and the screening of their photosensitization mechanisms.

Unravelling Melatonin’s Varied Antioxidizing Protection of Membrane Lipids Determined by its Spatial Distribution

“…Figure 3a shows the oxidation products of POPC by SO with the presence of different concentrations of M. Only the products 32 Da more than the parent protonated or sodiated POPC are observed at m/z 793 and 815, corresponding to the well-known peroxidation product POPC-OOH from the reaction between SO and olefins (Figure . S2b). 31 Surprisingly, the extent of POPC oxidation stays almost unchanged with increasing M concentrations (less than 5% fluctuation in Figure 3b), suggesting that M does not deliver antioxidation in this case, which agrees well with the situation depicted in Figure 1b. Figure 3c presents the FIDI mass spectrum of the oxidation products of M after 2 min oxidation by SO, which also displays extensive oxidation (vide infra).…”

“…S2b). Surprisingly, the extent of POPC oxidation stays almost unchanged with increasing M concentrations (less than 5% fluctuation in Figure b), suggesting that M does not deliver antioxidation in this case, which agrees well with the situation depicted in Figure b. Figure c presents the FIDI mass spectrum of the oxidation products of M after 2 min oxidation by SO, which also displays extensive oxidation ( vide infra ).…”

“…In this study, we adopt our unique home-built field-induced droplet ionization mass spectrometry (FIDI-MS) methodology (Figure c), which is capable of selective “online” in situ sampling of lipid monolayer membranes and their products that reside at the air–water interface right after the reactions without any sample handling or transfer and suffers minimal influence from the bulk of the solution. − We present the antioxidizing protection of POPC membranes by M against the hydroxyl radicals ( • OH) generated by the Fenton reaction in the water phase and singlet oxygen ( 1 O 2 , SO) generated by a lipophilic photosensitizer, 8-(4-chloromethylphenyl)-2,6-diiodo-1,3,5,7-tetramethyl dipyrrometheneboron difluoride (DI-BODIPY), in the lipid tail region (oil phase). Detailed experimental procedures are provided in the Supporting Information (SI).…”

“…Even though it is not the major topic of this study, here we briefly discuss the oxidation mechanisms by • OH and SO. The mechanisms for POPC oxidation have been previously reported , and provided in Figure S2. The proposed mechanisms for the oxidation of M by • OH and SO are exhibited in Figure a and b, respectively.…”

Free-Radical-Initiated Phospholipid Oxidations at the Air–Water Interface: The Oxidation of Unsaturated and Saturated Fatty Acid Chains

“…In this study, we focus on the oxidations of three representative amphiphilic phospholipids, 1-palmitoyl-2-oleoyl- sn -glycero-3-phospho-(1′- rac -glycerol) (POPG), 1-palmitoyl-2-oleoyl-glycero-3-phos­pho­choline (POPC), and 1,2-dipalmitoyl- sn -glycero-3-phos­pho­choline (DPPC), using TMDPO as the initiator under UV irradiation at the air–water interface. The home-developed field-induced droplet ionization mass spectrometry (FIDI-MS) methodology which can selectively sample monolayers of molecules that reside at the air–water interface and suffers minimal influence from the bulk solutions is employed in this study. − POPG and POPC are monounsaturated phospholipids where the CC double bonds are vulnerable to radical attack. DPPC with no unsaturated chains is used to confirm the possibility of the oxidation of saturated chains.…”