A novel mitochondria-targeted rhodamine analogue for the detection of viscosity changes in living cells, zebra fish and living mice

Guo, Rui; Yin, Junling; Ma, Yanyan; Wang, Qiuan; Lin, Weiying

doi:10.1039/c8tb00298c

“…Longer lifetimes and higher quantum yield of aldehyde 4 compared to nitrile 3 might illustrate that, contrary to molecular rotors, [2] the "brightness" of flippers reports on more than the number of rotatable bonds.I ndeed, the fluorescence intensities of non-amphiphilic derivatives of 1 and 2 decreased in increasingly viscous solvents (Figures 4e,f,F igure S16 in the Supporting Information). Such behavior is opposite to molecular rotors, [2] but consistent with the viscosity dependence of the excited state untwisting into the emissive planar form. [12] Thef luorescence decrease was accompanied by only as mall (< 10 nm) red shift of the excitation maximum (Figure 4e).…”

Section: Angewandte Chemiementioning

confidence: 99%

“…

Planarizable push-pull probes have been introduced to demonstrate physical forces in biology.However,the donors and acceptors needed to polarizem echanically planarized probes are incompatible with their twisted resting state.T he objective of this study was to overcome this "flipper dilemma" with chalcogen-bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe.T his concept is explored by molecular dynamics simulations as well as chemical double-mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability,red shifts adding up to high significance,and focused mechanosensitivity.M ost important, however,i st he introduction of an ew,g eneral and fundamental concept that operates with non-trivial supramolecular chemistry,solves an important practical problem and opens aw ide chemical space.Planarizable push-pull (PP) chromophores have been introduced [1] as mechanosensitive [2] fluorescent membrane probes [1][2][3] to image membrane tension [4] in living cells. [5,6] The current best is constructed around twisted dithienothiophene (DTT) dithienothiophene S,S-dioxide (DTTO2) conjugates ( Figure 1a,D ' = S, A' = SO 2 ).

…”

mentioning

confidence: 99%

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

Macchione

¹

,

Goujon

²

,

Straková

³

et al. 2019

View full text Add to dashboard Cite

Planarizable push-pull probes have been introduced to demonstrate physical forces in biology.However,the donors and acceptors needed to polarizem echanically planarized probes are incompatible with their twisted resting state.T he objective of this study was to overcome this "flipper dilemma" with chalcogen-bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe.T his concept is explored by molecular dynamics simulations as well as chemical double-mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability,red shifts adding up to high significance,and focused mechanosensitivity.M ost important, however,i st he introduction of an ew,g eneral and fundamental concept that operates with non-trivial supramolecular chemistry,solves an important practical problem and opens aw ide chemical space.Planarizable push-pull (PP) chromophores have been introduced [1] as mechanosensitive [2] fluorescent membrane probes [1][2][3] to image membrane tension [4] in living cells. [5,6] The current best is constructed around twisted dithienothiophene (DTT) dithienothiophene S,S-dioxide (DTTO2) conjugates ( Figure 1a,D ' = S, A' = SO 2 ). [7] Thet wo "flippers" [7] are twisted out of coplanarity by repulsion between the methyls (light blue circles) and the s holes (dark blue ovals) [8][9][10][11] on the sulfurs next to the connecting bond ( Figure 1b,l eft, 1). The PP system is prepared first with "sulfide" donors and "sulfone" acceptors in the DTT and the DTTO2b ridges, respectively (Figure 1b, 8,9). Conjugation of DTT and DTTO2u pon mechanical co-planarization then turns on this intrinsic PP system and shifts the excitation maximum to the red (Figure 1b,r ight). Thee mission maximum is nearly mechanoinsensitive because the probes emit only from the planar form. [12] To achieve significant red shifts upon planarization in the ground state,a dditional PP donors Da nd acceptors Aa re required (Figure 1a). These exocyclics ubstituents represent atrue dilemma because in the twisted resting state,the DTT donors and DTTO2 acceptors,a tl east partially decoupled from each other and equipped with extra Da nd A, could become too rich and too poor in electron density,respectively, and decompose easily (Figure 1a). Because both DTTs and DTTO2are comparably electron-rich, [13] this problem is more pronounced on the DTT side.T herefore,Dand As hould ideally turn on only in response to flipper planarization. Sulfides,p reviously introduced as covalent PP turn-on donors, [12] failed to afford operational probes. [14] Non-covalent 1,4-chalcogen bonds (1,4-CBs) [8][9][10][11] as in 1 were more successful, also because spontaneous degradation into reactive Figure 1. a) Flipper dilemma and b) CB cascade switch:a)Inplanarizable PP probes, exocyclic donors D D and acceptors A A are needed in planar but incompatiblew ith twisted form. b) Twisting of the central bond (1)turns off PP D D (2,r ed circle), and A A (3,b lue circle) because Lewis base Y( 5)hardly...

show abstract

“…Longer lifetimes and higher quantum yield of aldehyde 4 compared to nitrile 3 might illustrate that, contrary to molecular rotors, [2] the "brightness" of flippers reports on more than the number of rotatable bonds.I ndeed, the fluorescence intensities of non-amphiphilic derivatives of 1 and 2 decreased in increasingly viscous solvents (Figures 4e,f,F igure S16 in the Supporting Information). Such behavior is opposite to molecular rotors, [2] but consistent with the viscosity dependence of the excited state untwisting into the emissive planar form.…”

Section: In Memory Of Koji Nakanishimentioning

confidence: 99%

“…Cascade switched flipper probes turn out to excel with chemical stability,red shifts adding up to high significance,and focused mechanosensitivity.M ost important, however,i st he introduction of an ew,g eneral and fundamental concept that operates with non-trivial supramolecular chemistry,solves an important practical problem and opens aw ide chemical space.Planarizable push-pull (PP) chromophores have been introduced [1] as mechanosensitive [2] fluorescent membrane probes [1][2][3] to image membrane tension [4] in living cells. Cascade switched flipper probes turn out to excel with chemical stability,red shifts adding up to high significance,and focused mechanosensitivity.M ost important, however,i st he introduction of an ew,g eneral and fundamental concept that operates with non-trivial supramolecular chemistry,solves an important practical problem and opens aw ide chemical space.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

Macchione

¹

,

Goujon

²

,

Straková

³

et al. 2019

View full text Add to dashboard Cite

Planarizable push-pull probes have been introduced to demonstrate physical forces in biology.However,the donors and acceptors needed to polarizem echanically planarized probes are incompatible with their twisted resting state.T he objective of this study was to overcome this "flipper dilemma" with chalcogen-bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe.T his concept is explored by molecular dynamics simulations as well as chemical double-mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability,red shifts adding up to high significance,and focused mechanosensitivity.M ost important, however,i st he introduction of an ew,g eneral and fundamental concept that operates with non-trivial supramolecular chemistry,solves an important practical problem and opens aw ide chemical space.Planarizable push-pull (PP) chromophores have been introduced [1] as mechanosensitive [2] fluorescent membrane probes [1][2][3] to image membrane tension [4] in living cells. [5,6] The current best is constructed around twisted dithienothiophene (DTT) dithienothiophene S,S-dioxide (DTTO2) conjugates ( Figure 1a,D ' = S, A' = SO 2 ). [7] Thet wo "flippers" [7] are twisted out of coplanarity by repulsion between the methyls (light blue circles) and the s holes (dark blue ovals) [8][9][10][11] on the sulfurs next to the connecting bond (Figure 1b,l eft, 1). The PP system is prepared first with "sulfide" donors and "sulfone" acceptors in the DTT and the DTTO2b ridges, respectively (Figure 1b, 8,9). Conjugation of DTT and DTTO2u pon mechanical co-planarization then turns on this intrinsic PP system and shifts the excitation maximum to the red (Figure 1b,r ight). Thee mission maximum is nearly mechanoinsensitive because the probes emit only from the planar form. [12] To achieve significant red shifts upon planarization in the ground state,a dditional PP donors Da nd acceptors Aa re required (Figure 1a). These exocyclics ubstituents represent atrue dilemma because in the twisted resting state,the DTT donors and DTTO2 acceptors,a tl east partially decoupled from each other and equipped with extra Da nd A, could become too rich and too poor in electron density,respectively, and decompose easily (Figure 1a). Because both DTTs and DTTO2are comparably electron-rich, [13] this problem is more pronounced on the DTT side.T herefore,Dand As hould ideally turn on only in response to flipper planarization. Sulfides,p reviously introduced as covalent PP turn-on donors, [12] failed to afford operational probes. [14] Non-covalent 1,4-chalcogen bonds (1,4-CBs) [8][9][10][11] as in 1 were more successful, also because spontaneous degradation into reactive Figure 1. a) Flipper dilemma and b) CB cascade switch:a)Inplanarizable PP probes, exocyclic donors D D and acceptors A A are needed in planar but incompatiblew ith twisted form. b) Twisting of the central bond (1)turns off PP D D (2,r ed circle), and A A (3,b lue circle) because Lewis base Y( 5)hardly ...

show abstract

Fluorescent Membrane Tension Probes for Early Endosomes

Piazzolla

¹

,

Mercier

²

,

Assies

³

et al. 2021

View full text Add to dashboard Cite

Fluorescent flipper probes have been introduced recently to image membrane tension in live cells, and strategies to target these probes to specific membranes are emerging. In this context, early endosome (EE) targeting without the use of protein engineering is especially appealing because it translates into a fascinating transport problem. Weakly basic probes, commonly used to track the inside of acidic late endosomes and lysosomes, are poorly retained in EE because they are sufficiently neutralized in weakly acidic EE, thus able to diffuse out. Here, we disclose a rational strategy to target EE using a substituted benzylamine with a higher pKa value as a head group of the flipper probe. The resulting EE flippers are validated for preserved mechanosensitivity, ready for use in biology, particularly to elucidate the mechanics of endocytosis.

show abstract

A novel mitochondria-targeted rhodamine analogue for the detection of viscosity changes in living cells, zebra fish and living mice

Abstract: We designed a novel mitochondria-targeted rhodamine analogue for the detection of viscosity changes in living cells, zebra fish, and living mice.

Cited by 71 publications

References 32 publications

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

Fluorescent Membrane Tension Probes for Early Endosomes

Contact Info

Product

Resources

About