In this report, we introduce synthetic anion transporters that operate with chalcogen bonds. Electron-deficient dithieno[3,2-b;2',3'-d]thiophenes (DTTs) are identified as ideal to bind anions in the focal point of the σ holes on the cofacial endocyclic sulfur atoms. Anion binding in solution and anion transport across lipid bilayers are found to increase with the depth of the σ holes of the DTT anionophores. These results introduce DTTs and related architectures as a privileged motif to engineer chalcogen bonds into functional systems, complementary in scope to classics such as 2,2'-bipyrroles or 2,2'-bipyridines that operate with hydrogen bonds and lone pairs, respectively.

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...

Using chemical genetics, we show that acute inhibition of otherwise rapamycin-insensitive TORC2 triggers a slow increase in plasma membrane tension that provokes snapping of the bonds between adaptor proteins and polymerizing actin filaments and ultimately the cessation of endocytosis in yeast.

The design, synthesis, and evaluation of multifunctional dithieno[3,2‐b;2′,3′‐d]thiophene (DTT) trimers is described. Twisted push‐push‐pull or donor‐donor‐acceptor (DDA) trimers composed of one DTT acceptor and two DTT donors show strong mechanochromism in lipid bilayer membranes. Red shifts in excitation rather than emission and fluorescence recovery with increasing membrane order are consistent with planarization of the twisted, extra‐long mechanophores in the ground state. The complementary pull‐pull‐pull or AAA trimers with deep σ holes all along the scaffold are not mechanochromic in membranes but excel with submicromolar anion transport activity. Anion transport along membrane‐spanning strings of chalcogen‐bond donors is unprecedented and completes previous results on transmembrane cascades that operate with equally unorthodox interactions such as halogen bonds and anion‐π interactions.