Intra- and intermolecular fluorescence quenching of N-activated 4,5-dimethoxyphthalimides by sulfides, amines, and alkyl carboxylates

Griesbeck, Axel G.; Schieffer, Stefan

doi:10.1039/b211008c

Cited by 28 publications

(24 citation statements)

References 25 publications

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“…These probes take advantage of the highly reactive natural amino acid methionine that is converted to the sulfoxide, a process that can also be reversed by methionine sulfoxide reductase. In intermolecular quenching studies, we have already identified the strong intermolecular fluorescence quenching of fluorescent phthalimides by thioethers . In the new probes, donor‐substituted phthalimides are used as fluorophores and methionine derivatives as the 1 O 2 ‐sensitive parts .…”

Section: Resultsmentioning

confidence: 99%

New phthalimide‐methionine dyad‐based fluorescence probes for reactive oxygen species: Singlet oxygen, hydrogen peroxide, and hypochlorite

Griesbeck

Öngel

Atar

2017

J of Physical Organic Chem

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Different reactive oxygen species were detected by the molecular probes 1-3 that were composed of the phthalimide fluorophore as reporter and a methionine-derived thioether side-chain as receptor part. The sulfoxides that were formed as the primary oxidation products show strong fluorescence in the blue-green (430-540 nm) spectral region. Self-sensitized oxidation by singlet oxygen is in general inefficient indicating rapid electron-transfer quenching of the excited probe molecules. With hydrogen peroxide as thermal oxidant conversion to the sulfoxides is slow but can be accelerated by addition of titanium(IV) catalysts, whereas hypochlorite as oxidant behaves much more reactive even under uncatalyzed conditions. Singlet oxygen that is generated by energy transfer from the photosensitizer Rose Bengal was detected by sensor 1a with rate constants of >10 7 M -1 s -1 , a typical rate constant for the oxidation of thioethers to sulfoxides.

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Section: Resultsmentioning

confidence: 99%

New phthalimide‐methionine dyad‐based fluorescence probes for reactive oxygen species: Singlet oxygen, hydrogen peroxide, and hypochlorite

Griesbeck

Öngel

Atar

2017

J of Physical Organic Chem

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“…18 Much to our delight, 1c turned out to be a reactive substrate for the photodecarboxylation with 3,4,5-trimethoxyphenylacetate 2d (Scheme 4). 19 In this special case, application of the electron-rich aryl group in the donor substrate seems to accelerate the electron transfer process.…”

Section: Methodsmentioning

confidence: 98%

Photodecarboxylative Benzylation ofN-Alkylphthalimides: A Concise Route to the Aristolactam Skeleton

Griesbeck¹,

Warzecha²,

Neudörfl³

et al. 2004

Synlett

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The photoinitiated metal-free benzylation of N-alkyl phthalimides with arylacetates in aqueous solution followed by acid-catalyzed dehydration serves as a convenient route to methoxy-substituted precursors to phenanthrene lactam alkaloids.Aristolactams 1 I constitute a group of phenanthrene lactam alkaloids from the Aristolochia genus with promising pharmacological activities. While the corresponding nitrophenanthrene carboxylic acids, e.g. aristolochic acid IV (II R 6 = R 8 = OCH 3 , Figure 1), often found in the same plants, cause nephropathy with a high risk for urothelial cancer in humans (aristolochic acid nephropathy, AAN), 2 the aristolactams are potent inhibitors of platelet aggregation and show significant cytotoxicity against different tumor cell lines. Figure 1Structural variations of the natural aristolactams include methyl groups at the amide nitrogen, e.g. in the recently discovered piperolactam E (R 1 = R 2 = OCH 3 , R 3 = OH, R 4 = CH 3 ) 3 as well as a broad methoxy substitution pattern.A straightforward synthetic approach has been developed by the Couture group applying as key step the lithiation of halogenated N-phosphorylbenzamides, cyclization of the aryne intermediate, Horner olefination of the phosphorylated aminocarbanion and Pd-catalyzed arene-arene coupling. 4 We wish to describe an alternative photochemical concept. Since a direct oxidative arene coupling also appears feasible for the isoindolinone case, i.e. for the phenanthrene ring closure (A → I), we envisaged the synthesis of arylalkylidene isoindolinones A with the appropriate Ealkene configuration (Scheme 1). Consequently, the benzylation of symmetric phthalimides C with arylacetic acids D and subsequent acid-catalyzed dehydration of the 3-benzyl-3-hydroxyisoindolin-1-ones B appears as a short and simple approach to the desired stilbene skeletons. Moreover, a straightforward access to both A and B is of general interest due to their biological potential. 5 Scheme 1The photodecarboxylative addition of alkyl carboxylates to N-substituted phthalimides via photoinduced electron transfer (PET) represents a metal-free variant of the traditional Grignard-type alkylation of phthalimides. 6 In the previous decade we have developed this approach beyond the use of simple alkyl carboxylates (corresponding to imide alkylation) 7 to a-ketocarboxylates 8 and a-heteroatom substituted alkyl carboxylates. 9 Especially the latter variants show the potential of this reaction, i.e. solely the carboxylate group is activated after the primary electronic excitation of the phthalimide chromophore and these processes can easily be upscaled to the 20-40 g scale by applying excimer radiation technology. 10 As we have already demonstrated, 7,10 benzylation of N-methylphthalimide with phenylacetate is a straightforward and highyielding process.A synthetically relevant as well as mechanistically appealing question was whether this pivotal benzylation step tolerates additional electron-donating substituents at both arene components, i.e. the phthalimide subs...

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“…The fluorescence quenching of the model compound 3,4-dimethoxy N-methyl phthalimide (DMMP) by dimethyl sulfide was recently investigated and dynamic quenching with a Stern-Volmer constant K SV of 59 M À 1 was determined in methylene chloride. [15] In order to correlate this with the compounds described in this publication, the Nbutyl derivative 6 was investigated and also fluorescence lifetimes were determined for 6 and the N-methyl derivative in acetonitrile. In acetonitrile, the undisturbed fluorescence of phthalimide 6 decays monoexponential with τ F = 32 ns and is quenched by external dimethylsulfide (Figure 7).…”

Section: Intermolecular Fluorescence Quenchingmentioning

confidence: 99%

“…[12][13][14] An especially successful approach was the 4,5dialkoxyphthalimide that shows strong fluorescence with quantum yields near to 100 %. [15] Strongly fluorescent phthalimides that also constitute very strong reductants in the excited singlet states have been developed as excellent sensors for anions such as fluoride, [16,17] or cyanide. [18] Recently, we have developed phthalimide probes for singlet oxygen and hydrogen peroxide that operate by fluorescence ON effects and were based on 4,5-dialkoxyphthalimides with internal fluorescence quenching groups.…”

Section: Introductionmentioning

confidence: 99%

“…[19] This concept is based on the known fluorescence quenching/sensor properties of thiols [20,21] and thioethers with respect to phthalimide chromophores. [15] In this paper, we describe an extensive study of the photophysical properties of thioalkylated and thioarylated phthalimides and the corresponding structural interpretations of their fluorescence properties.…”

Section: Introductionmentioning

confidence: 99%

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Intra‐ and Intermolecular Fluorescence Quenching of Alkylthio‐Substituted Phthalimides by Photoinduced Electron Transfer: Distance, Position and Conformational Dependence

et al. 2019

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The photophysical properties of fluorescent phthalimides with thioether groups directly connected to the chromophore or separated by alkyl spacers, respectively, were studied. Intermolecular fluorescence quenching by electron transfer from dimethylsulfide to the 4,5-dimethoxy phthalimide (DMPht) model compound 6 is dynamic and fast. The fluorescence properties of 6 and the remote C 5 -spaced thioether derivative 5 are nearly identical. In compounds 1-4 with shorter spacer lengths, fluorescence quenching is strong for C 2 and C 3 -spaced 2 and 3 and less pronounced for C 1 -and C 4 -spaced compounds 1 and 4, mapping the conformational landscape of these molecules. The o-,m-,p-substituted N-(thiomethyl)benzyl DMPht 7 are almost non-fluorescent which correlates very well with the intermolecular thioanisole fluorescence quenching of 6. In contrast, the 3-and 4-thiomethyl phthalimides 8 and 9 show divergent fluorescence that is also rationalized by DFT calculation results. The fluorescence properties can be switched by oxidation of the thioethers to sulfoxides with H 2 O 2 or 1 O 2 (off! on for 1,4,7 and on!off for 9). Further functionalized molecules that were based on the model compounds are the sulfurcontaining amino acid methionine derivative 10, dipeptides 11 a,b, and S-alkylated cysteine derivatives 12 to 14 a-d with strong side-chain-dependent fluorescence.[a] Dr.

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Intra- and intermolecular fluorescence quenching of N-activated 4,5-dimethoxyphthalimides by sulfides, amines, and alkyl carboxylates

Cited by 28 publications

References 25 publications

New phthalimide‐methionine dyad‐based fluorescence probes for reactive oxygen species: Singlet oxygen, hydrogen peroxide, and hypochlorite

New phthalimide‐methionine dyad‐based fluorescence probes for reactive oxygen species: Singlet oxygen, hydrogen peroxide, and hypochlorite

Photodecarboxylative Benzylation ofN-Alkylphthalimides: A Concise Route to the Aristolactam Skeleton

Intra‐ and Intermolecular Fluorescence Quenching of Alkylthio‐Substituted Phthalimides by Photoinduced Electron Transfer: Distance, Position and Conformational Dependence

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