Synthesis and Singlet Oxygen Reactivity of 1,2‐Diaryloxyethenes and Selected Sulfur and Nitrogen Analogs

Nkepang, Gregory; Pogula, Praveen K.; Bio, Moses; You, Youngjae

doi:10.1111/j.1751-1097.2012.01095.x

Cited by 14 publications

(12 citation statements)

References 41 publications

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“…We have not computed the transition structures connecting 4 with 8 and 9 that must be computed in both the ground and excited states. By analogy, excited‐state carbonyl products are formed in the decomposition of conventional 1,2‐dioxetanes .…”

Section: Resultsmentioning

confidence: 99%

Theoretical Study of the Reaction Formalhydrazone with Singlet Oxygen. Fragmentation of the C=N Bond, Ene Reaction and Other Processes

Rudshteyn

Castillo

Ghogare

et al. 2013

Photochem & Photobiology

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Photobiologic and synthetic versatility of hydrazones has not yet been established with 1O2 as a route to commonly encountered nitrosamines. Thus, to determine whether the “parent” reaction of formalhydrazone and 1O2 leads to facile C=N bond cleavage and resulting nitrosamine formation, we have carried out CCSD(T)//DFT calculations and analyzed the energetics of the oxidation pathways. A [2 + 2] pathway occurs via diradicals and formation of 3-amino-1,2,3-dioxazetidine in a 16 kcal/mol process. Reversible addition or physical quenching of 1O2 occurs either on the formalhydrazone carbon for triplet diradicals at 2–3 kcal/mol, or on the nitrogen (N(3)) atom forming zwitterions at ~15 kcal/mol, although the quenching channel by charge-transfer interaction was not computed. The computations also predict a facile conversion of formalhydrazone and 1O2 to hydroperoxymethyl diazene in a low-barrier ‘ene’ process, but no 2-amino-oxaziridine-O-oxide (perepoxide-like) intermediate was found. A Benson-like analysis (group increment calculations) on the closed shell species are in accord with the quantum chemical results.

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Section: Resultsmentioning

confidence: 99%

Theoretical Study of the Reaction Formalhydrazone with Singlet Oxygen. Fragmentation of the C=N Bond, Ene Reaction and Other Processes

Rudshteyn

Castillo

Ghogare

et al. 2013

Photochem & Photobiology

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“…For example, various cis/trans-substituted alkenes were reported to react with singlet oxygen, followed by decomposition to give clean corresponding carbonyl compounds [49,57,64,65]. When the substituted double bonds were used as a photocleavable linker, a lighttriggered release of greater than 90% of the conjugated reagents was reported, i.e., in [54,57,64,65]. Such a cleavage mechanism has been thoroughly investigated and utilized by a number of investigators to, for example, prepare carbonyl-containing compounds in organic synthesis [54], create prodrugs from drugs bearing a carbonyl group [57], release drugs from liposomes [58][59][60], release and precipitate photosensitizers at targeted sites [61], or deliver photosensitizers from a glass tip [62].…”

Section: Development Of Singlet-oxygen-sensitive Linkermentioning

confidence: 99%

“…The reaction of singlet oxygen and an alkene can be exclusively directed through [2+2] cycloaddition, leading to clean products from decomposition of the dioxetane intermediate [50,51,55,63]. For example, various cis/trans-substituted alkenes were reported to react with singlet oxygen, followed by decomposition to give clean corresponding carbonyl compounds [49,57,64,65]. When the substituted double bonds were used as a photocleavable linker, a light-triggered release of greater than 90% of the conjugated reagents was reported, i.e., in [54,57,64,65].…”

Section: Development Of Singlet-oxygen-sensitive Linkermentioning

confidence: 99%

Section: Development Of Singlet-oxygen-sensitive Linkermentioning

confidence: 99%

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Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology

Nguyen

Woo

et al. 2019

JCM

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Photodynamic therapy (PDT) has become an effective treatment for certain types of solid tumors. The combination of PDT with other therapies has been extensively investigated in recent years to improve its effectiveness and expand its applications. This focused review summarizes the development of a prodrug system in which anticancer drugs are activated locally at tumor sites during PDT treatment. The development of a singlet-oxygen-sensitive linker that can be conveniently conjugated to various drugs and efficiently cleaved to release intact drugs is recapitulated. The initial design of prodrugs, preliminary efficacy evaluation, pharmacokinetics study, and optimization using quantitative systems pharmacology is discussed. Current treatment optimization in animal models using physiologically based a pharmacokinetic (PBPK) modeling approach is also explored. prodrug specifically at the tumor site when PDT treatment is initiated. The drug provides a sustained and extended cell-killing effect, in addition to local damage produced by PDT. While there are a number of other reviews about prodrugs and PDT [9,16,[33][34][35][36][37][38], this case review summarizes the singlet-oxygen-activatable prodrug system developed in our lab, specifically focusing on development of our unique cleavable linker triggered by singlet oxygen, initial evaluation of photodynamic prodrugs utilizing the singlet-oxygen-sensitive linker, quantitative systems pharmacologic analysis, and current optimization aided by physiologically based pharmacokinetic modeling in animal models. Development of Singlet-Oxygen-Sensitive LinkerPhotocleavable bonds have long been investigated and used in numerous applications, such as in organic synthesis, drug delivery, and the study of intracellular biochemical processes (e.g., signaling pathways, gene expression) [39][40][41][42][43][44][45]. Light is a major component of PDT; however, the preferred wavelengths-to facilitate deeper penetration in tissue-are in the red and far-red regions, limiting the choices of linkers that are directly cleaved by such low-energy light [44][45][46][47]. In our prodrug system, we exploited a unique bond cleavage phenomenon mediated by singlet oxygen, which is generated during the PDT process, to overcome this problem. The cleavage mechanism is based on a well-known property of the double bond to participate in a [2+2] cycloaddition with singlet oxygen following decomposition to ultimately give carbonyl fragments via a dioxetane intermediate (Figure 1a) [48][49][50][51][52][53][54][55][56].

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“…It is a sensitizer‐capped device with a photolabile di‐ O‐ vinyl ether bridge that releases the pheophorebide stored on the cap via attack of singlet oxygen from sensitization of the oxygen gas delivered through the hollow fiber using 669 nm laser light. O‐ Vinyl ethers are useful for photocleaving reactions at the double bond, a number of them react with 1 O 2 by mechanisms involving dioxetane intermediates . Probe tip 1 has since been modified to probe tip 2 to improve the release action of the pheophorbide sensitizer .…”

Section: Introductionmentioning

confidence: 99%

A Fiberoptic (Photodynamic Therapy Type) Device with a Photosensitizer and Singlet Oxygen Delivery Probe Tip for Ovarian Cancer Cell Killing

Bartusik

Aebisher

Ghogare

et al. 2013

Photochem & Photobiology

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A portable “fiber optic-based sensitizer delivery” device has been developed and studied. Before there might be success in photodynamic therapy (PDT) and anti-bacterial ambitions, an understanding of basic factors on device performance were needed. Thus, the device was examined for the localized delivery of sensitizer molecules in ovarian cancer cells and production of high concentrations of singlet oxygen for their eradication in vitro. The device-tip releases stored pheophorebide by attack of singlet oxygen from sensitized oxygen gas delivered through the hollow fiber using 669-nm laser light. The performance of the device was enhanced when configured with a fluorosiliane tip by virtue of its Teflon-like property compared to a conventional glass tip (greater sensitizer quantities photoreleased and laterally diffused, and greater amounts of ovarian OVCAR-5 cancer cell killing). No cell damage was observed at 2.2 N of force applied by the probe tip itself, an amount used for many of the experiments described here.

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Synthesis and Singlet Oxygen Reactivity of 1,2‐Diaryloxyethenes and Selected Sulfur and Nitrogen Analogs

Cited by 14 publications

References 41 publications

Theoretical Study of the Reaction Formalhydrazone with Singlet Oxygen. Fragmentation of the C=N Bond, Ene Reaction and Other Processes

Theoretical Study of the Reaction Formalhydrazone with Singlet Oxygen. Fragmentation of the C=N Bond, Ene Reaction and Other Processes

Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology

A Fiberoptic (Photodynamic Therapy Type) Device with a Photosensitizer and Singlet Oxygen Delivery Probe Tip for Ovarian Cancer Cell Killing

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