Aggregation-Enhanced Excimer Emission of Tetraarylethene Linkers in Ladderphanes

Abstract

Tetraarylethene (TAE) has been used as linkers in polynorbornene- and polycyclobutene-based double-stranded ladderphanes and as pendants in related single-stranded polymers. The adjacent TAE linkers in these polymers are separated by 4.5–5.5 Å. Upon irradiation at 315 nm in dichloromethane (DCM), TAE excimer emission is observed at 493 nm with quantum yield Φ = 0.005–0.015. When MeOH/DCM (3/1) is used as the medium, Φs of hexyloxy-substituted TAE ladderphanes increase to 0.45–0.48 due to aggregation-enhanced excimer emission (AEEE). TAE-appended single-stranded polynorbornene has Φ = 0.21 under the same conditions. The neighboring TAE chromophores in these single-stranded polymers may not be eclipsed and therefore might be less favored for excimer formation. Entangling of hexyloxy groups, inter alia, may be responsible for AEEE. Replacement of a hexyloxy group by a methoxy group leads to a reduction in the quantum yield by 70% due to lack of entangling. The overall process that is responsible for AEEE involves excimer formation, aggregation of polymers, plus entangling of long-chain alkyl groups.

Cyclic–hanging-multicyclic polymer synthesized by ladderphane-mediated blocking-cyclization technique for the direct visualization of cyclic macromolecular topology

“…30,31 In contrast to the traditional methods for synthesizing cyclic polymers, this method possesses some prominent features, including the direct use of the commercial catalyst, permitting a relatively high monomer concentration, the availability of a cyclic structure with high purity and without the treatments of separation and purification of the linear polymer precursor, owing to using the short ladderphane as the multiple cyclizing unit. 29,32 However, how to develop an efficient route for the synthesis of multicyclic polymers with a complex cyclic topology and plenty of cyclic macromolecular units remains a great challenge, and the direct visualization of cyclic molecular topology was still rarely realized. On the basis of the previous investigation, we proposed a feasible and convenient route for the construction of cyclic-hanging-multicyclic polymers by a ROMP-based blocking-cyclization technique [29][30][31] of a bulky cyclic side chain-contained norbornene macromonomer, which was obtained by a rhodanine-mediated ROP of episulfide, 28 and then transformed into the main chain of cyclic polynorbornene bearing multicyclic polythioether side chains.…”

FAP-α-Instructed Coumarin Excimer Formation for High Contrast Fluorescence Imaging of Tumor

“…21,22 The dual aggregation processes may synergistically enhance the excimer emission of a planar polycyclic aromatic fluorophore (e. coumarin): (1) the rigid cyclic dimer would bring two coumarin molecules to a close proximity to facilitate the formation of an intramolecular excimer, 23 additionally suppressing the nonradiative decay of the excimer and consequently converting the energy into photons; 24,25 (2) the intermolecular π−π stacking between the discrete dimers may work as secondary interactions to stabilize the coumarin excimer and enhance its emission. 26,27 Hence, as a proof-of-concept, we designed a "smart" fluorescence probe Cbz-Gly-Pro-Cys(StBu)-Lys(coumarin)-CBT (Cbz-GPC(StBu)K(Cou)-CBT), which, upon fibroblast activation protein alpha (FAP-α)-activation, subjected to the CBT-Cys click reaction self-assembles into nanoparticle Cou-CBT-NP, turning coumarin excimer fluorescence "on" for high contrast tumor imaging. As a type-II transmembrane serine protease, FAP-α is overexpressed in more than 90% of epithelial tumors but negligible in almost all normal tissues in humans.…”

“…33 The as-formed monodispersed nanoparticles (i.e., Cou-CBT-NPs, average diameter 72.3 ± 9.5 nm, Figures 2d, S28, and S29) by the H-aggregates further stabilized the excimer and enhanced its emission. 26,27 We further investigated the selectivity of Cbz-GPC(StBu)K-(Cou)-CBT toward FAP-α by recording the fluorescence intensity at 550 nm of the probe after incubation with various tumor-overexpressing enzymes, including alkaline phosphatase (ALP), carboxylesterase (CES), γ-glutamyl transferase (GGT), caspase-3, urokinase-type plasminogen activator (uPA), aminopeptidase N (APN), tyrosinase, or FAP-α, respectively. As shown in Figure S30, only FAP-α could effectively activate the probe to yield a strong emission at 550 nm, indicating the excellent selectivity of Cbz-GPC(StBu)K(Cou)-CBT toward FAP-α.…”

“…Because, in principle, the probe molecule flanked by 2-cyano-6-aminobenzothiazole (CBT) and cysteine (Cys) can easily react with one another to form a cyclic dimer, which further self-assembles into nanoparticles through π–π stacking in mild physiological conditions. As a result, this reaction enables both intra- and intermolecular aggregations of the excimer-forming dyes conjugated to the molecule backbone. , The dual aggregation processes may synergistically enhance the excimer emission of a planar polycyclic aromatic fluorophore (e.g., coumarin): (1) the rigid cyclic dimer would bring two coumarin molecules to a close proximity to facilitate the formation of an intramolecular excimer, additionally suppressing the nonradiative decay of the excimer and consequently converting the energy into photons; , (2) the intermolecular π–π stacking between the discrete dimers may work as secondary interactions to stabilize the coumarin excimer and enhance its emission. , …”

“…First, FAP-α cleavage of Cbz-GPC­(StBu)­K­(Cou)-CBT induced the formation of rigid cyclic dimer Cou-CBT-Dimer (see Figure S24 for the chemical structure), which restricted two coumarin molecules to a close proximity to form the intramolecular emissive excimer. − Second, Cou-CBT-Dimer promoted the coumarin excimer formation by forming H-aggregates, which was verified by a characteristic hypsochromic shift in the excitation spectra of Cbz-GPC­(StBu)­K­(Cou)-CBT (Figure S27). The as-formed monodispersed nanoparticles (i.e., Cou-CBT-NPs , average diameter 72.3 ± 9.5 nm, Figures d, S28, and S29) by the H-aggregates further stabilized the excimer and enhanced its emission. , We further investigated the selectivity of Cbz-GPC­(StBu)­K­(Cou)-CBT toward FAP-α by recording the fluorescence intensity at 550 nm of the probe after incubation with various tumor-overexpressing enzymes, including alkaline phosphatase (ALP), carboxylesterase (CES), γ-glutamyl transferase (GGT), caspase-3, urokinase-type plasminogen activator (uPA), aminopeptidase N (APN), tyrosinase, or FAP-α, respectively. As shown in Figure S30, only FAP-α could effectively activate the probe to yield a strong emission at 550 nm, indicating the excellent selectivity of Cbz-GPC­(StBu)­K­(Cou)-CBT toward FAP-α.…”