In recent years, a myriad of organic and inorganic smart materials has been created to sense ultrasound, with enormous applications in navigation, diagnosis, imaging, and so on [1-5]. Among these ultrasound-responsive materials, mechanochromic polymers based on mechanophores exhibit an excellent capacity to change their photophysical properties upon exposure to ultrasound in solution, which has recently fascinated chemists due to their versatile designs and potential applications [6-12]. However, the activation of these covalent-bond-scission-based mechanochromic polymers preferably occurs in the solution state under an acoustic field, thus severely limiting their practical utilization. Differently, the supramolecular metal-ligand (M-L) complex as a dynamic mechanochromic moiety makes it possible to realize a highly reversible and sensitive response to ultrasound in the quasi-solid state with relatively lower acoustic energy [13-19].

Hydrogels are an attractive class of intelligent materials due to their highly water-swollen quasi-solid feature, exhibiting unique properties of both solid and liquid, including intrinsic soft and wet nature, multistimulus responsiveness [20-43]. By virtue of these merits, the dynamic hydrogels offer an ideal platform to develop ultrasound-responsive materials by incorporating reversible M-L interactions. Importantly, it may provide new insights into sonochemical effects to advance the understanding of mechanochemical transformation in the quasi-solid [44]. Compared with those polymers that can only respond in the solution, the ultrasound-responsive hydrogels hold great promise in diverse biomedical applications including diagnosis, imaging, and biosensing.

Herein, we report a feasible strategy to fabricate ultrasound-responsive supramolecular hydrogels through the combination of labile terpyridine-europium complex (TPY-Eu³⁺) as a mechanochromic moiety and an ultrasound-responsive fluorogen (URF) as a molecular tweezer (Scheme 1). In the fabrication process of ultrasound-responsive hydrogels, firstly, the terpyridine-functionalized monomer TPY-M was synthesized through two steps of nucleophilic substitution reactions in decent yields (Scheme S1 in Supporting information). The hydrophobic URF was synthesized by introducing two tetraphenylethylene (TPE) groups onto the 6,6″ position of TPY core through Suzuki coupling as outlined in Scheme S2 (Supporting information). The TPE groups on URF not only serve as luminophores to guarantee the efficient emission based on aggregation-induced emission (AIE) [45-53], but also act as bulky groups to inhibit coordination without the assistance of ultrasound in the hydrogel matrix. Both TPY-M and URF were completely verified by nuclear magnetic resonance (NMR), including ¹H, ¹³C, two-dimensional correlation spectroscopy (2D-COZY), nuclear Overhauser effect spectroscopy (2D-NOESY), high-resolution electrospray ionization time-of-flight (ESI-TOF) mass spectrometer (Figs. S1-S8, S10 and S11 in Supporting information).

Subsequently, TPY-M hydrogel was prepared by free-radical copolymerization of acrylamide (AAm), TPY-M, methylene bisacrylamide (MBAA) crosslinker, using AIBN as the thermal initiator in DMSO, followed by the solvent exchange in deionized water (Scheme S3 in Supporting information). The ultrasound-responsive hydrogel TPY-M-Eu was prepared by immersing TPY-M hydrogel into a solution of Eu(NO₃)₃ at room temperature. Likewise, ultrasound-responsive hydrogel TPY-M-URF-Eu was prepared by incorporating URF into the chemically crosslinked polymer network, followed by solvent exchange and coordination (see Supporting information for details). The chemical structures and compositions of hydrogels were thoroughly investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy (Fig. S20 in Supporting information) and X-ray photoelectron spectroscopy (XPS) experiments (Fig. S22 in Supporting information).

We reasoned that through introducing AIE luminogens (AIEgen), the hydrogels would exhibit remarkable emission efficiency. Indeed, as displayed in Fig. S14 (Supporting information), the TPY-M-URF hydrogel emits intense green fluorescence (centered at ca. 500 nm). Particularly, the emission of TPY-M-URF-Eu hydrogel displays strong yellowish fluorescent color, which is the overlapping luminescence of the URF and TPY-Eu³⁺ coordination complex. The fluorescent spectrum of TPY-M-URF-Eu hydrogel reveals two main parts centered at around 500 nm from URF, 590 nm, 615 nm and 690 nm attributed to the TPY-Eu³⁺ complex [15, 54], respectively. It indicates that no coordination occurs spontaneously between URF and Eu³⁺. Ultraviolet−visible (UV−vis) titration and NMR experiments also demonstrate that URF is unable to bind with Eu³⁺ in organic solvents even under sonication (Figs. S9 and S12 in Supporting information).

However, upon the irradiation of ultrasound, the emission band centered at ca. 500 nm was decreased over time, indicating that URF was consecutively coordinated with Eu³⁺ ions in the matrix of TPY-M-URF-Eu hydrogel (Fig. 1a). It is reflected in a decrease of the I₅₀₀/I₆₁₅ ratio (Fig. S15 in Supporting information). The I₅₀₀/I₆₁₅ fluorescent ratio decreased dramatically from 0.58 to 0.30 in the initial 10 mins and reached a plateau after ca. 40 min. It resulted in obvious fluorescence color-changing from bright yellowish (0.35, 0.44) to orange (0.52, 0.37) at the 1931 Commission Internationale de L'Eclairage (CIE) chromaticity diagram (Fig. 1b). Similarly, the emission intensity of TPY-M-Eu hydrogel underwent a considerable decrease upon sonication owing to the dissociation of TPY-Eu³⁺ assembly [16-18]. These results manifested that ultrasound-responsive hydrogels presented excellent color changes when subjected to ultrasonic irradiation, and also suggested the mechanochemical transformation taking place in the hydrogel matrix.

It was proposed that the dynamic TPY-Eu³⁺ complex was disassembled along with releasing of URF from aggregation, followed by the formation of a more stable URF-Eu³⁺ assembly when TPY-M-URF-Eu hydrogel was subjected to ultrasonic irradiation (Fig. 1c) [55]. Compared with the conformation in the organic solvents, the energy-minimized structure of URF preferably adopted a folded conformation in the hydrogel matrix. Thus, URF was capable of capturing Eu³⁺ like a molecular tweezer to form a stable supramolecular assembly. Subsequently, the URF-Eu³⁺ assembly might be further stabilized by the residual groups of polymer chains in the hydrogel network. After coordination, the URF served as a UV absorbing ligand to enable the emission of Eu(Ⅲ) through a ligand-to-metal energy-transfer process, i.e., "antenna effect" [56].

To further investigate the structural conformations of URF and TPY subunit in the hydrogel matrix, molecular dynamics (MD) simulations were further conducted by using the two torsion angles (N-C-C-N) as collective variables (Fig. 2 and Fig. S24 in Supporting information). Intriguingly, the free energy landscape of TPY subunit is highly symmetrical with a free energy barrier of ~20 kJ/mol (Fig. 2a), while the free energy landscape of URF is less symmetrical with a much higher free energy barrier of ~90 kJ/mol (Fig. 2b). It implies that the conformational space of URF is more confined to bind with Eu³⁺ due to the bulky size of TPE groups. The free energy profile along one dihedral is shown in Fig. 2c. Both the free energy minimum of the TPY subunit and URF have small dihedral angles with the three nitrogen atoms close to each other (inset of Fig. 2c). It also demonstrates that the optimized structure of URF in the hydrogel matrix is prone to adopt a folded conformation due to its hydrophobic feature. The calculated binding energies of Eu³⁺ with URF and TPY subunit are −48.52 eV and −41.26 eV, respectively. Prominently, it will be more difficult for Eu³⁺ to extricate from URF entrapment than the TPY subunit if hydrophilic and hydrophobic factors are taken into account. That is probably why the coordination bonds of TPY-Eu³⁺ were disrupted while the supramolecular URF-Eu³⁺ complex was assembled simultaneously in the hydrogel matrix upon the irradiation of ultrasound. The MD simulation and theoretical calculation demonstrate that the fluorescence response of TPY-M-URF-Eu hydrogel results from the mechanochemical transformation of europium(Ⅲ) complexes.

To gain more insights into the mechanism of sonochemical effect, electrochemical experiments were performed to probe the dissociation of the labile TPY-Eu³⁺ complex upon sonication (Fig. 3a). The output signal intensity of the relative current change ΔI/I₀ was consecutively increased to 7.8% when the TPY-M-Eu hydrogel was subjected to ultrasonic irradiation (Fig. 3b). It suggested that the mobile europium ions were increased under acoustic cavitation owing to the disassembly of the TPY-Eu³⁺ complex. The relative current returned to its initial value gradually at an ultrasound-free state because of the rebinding of the coordination bonds. Notably, the relative current was further increased with the increment of ultrasonic power (from 150 W to 300 W) and longer duration (200 s) as shown in Fig. 3c, indicating that the extent of disassembly could be tuned by varying acoustic energy and duration. To verify the role of the weak coordination bonds, the TPY-M hydrogel served as a control. By comparison, there was no significant change of output current when TPY-M hydrogel was subjected to ultrasonic irradiation (Fig. S23 in Supporting information). These results manifested that the dynamic coordination bonds of TPY-Eu³⁺ were dissociated at an acoustic field so that there were more mobile Eu³⁺ in the hydrogel matrix, leading to the increases of current.

Moreover, XPS experiments were carried out to study the sonochemical transformation of europium(Ⅲ) complexes in TPY-M-URF-Eu hydrogel at an acoustic field (Fig. 4a). After sonication, the intensity of peaks at around 1151.4 eV (Eu 3d_3/2) and 1121.8 eV (Eu 3d_5/2) for TPY-M-URF-Eu-US hydrogel were blueshifted from 1152.4 eV and 1122.4 eV for TPY-M-URF-Eu hydrogel, respectively, due to the coordination of the URF with Eu³⁺ (Fig. 4b). Also, because of the stronger electron-donating ability of URF than TPY subunit, downshifts of Eu 4d_3/2 and Eu 4d_5/2 from 131.6 eV and 126.0 eV for TPY-M-URF-Eu hydrogel to 131.2 eV and 125.7 eV, respectively, for TPY-M-URF-Eu-US hydrogel, indicating the formation of URF-Eu³⁺ assembly (Fig. 4c). Additionally, the transformation of europium(Ⅲ) complexes upon sonication were further investigated by ATR-FTIR spectroscopy. As revealed in Fig. S21 (Supporting information), the stretching vibrations of pyridine ring (C=N, C=C) moved from 1600.6 cm⁻¹ for TPY-M-URF-Eu hydrogel to 1598.6 cm⁻¹ for TPY-M-URF-Eu-US hydrogel. These results confirmed that the URF-Eu³⁺ complex was assembled in the hydrogel matrix upon ultrasound irradiation, leading to visible fluorescence color-changing.

In summary, our study provides new prospects for fabricating ultrasound-responsive hydrogel materials via the combination of supramolecular labile TPY-Eu³⁺ bonds and URF, where the TPY-Eu³⁺ complex servers as mechanochromic moiety and europium ion source, and URF acts like a molecular tweezer to capture mobile Eu³⁺. The disassembly of TPY-Eu³⁺ complexes and the formation of supramolecular URF-Eu³⁺ assembly leads to a notable fluorescence change in response to ultrasound. The mechanochemical transformation of europium(Ⅲ) complexes in hydrogel matrix have been demonstrated by MD simulations and evidenced by electrochemical experiments, XPS and ATR-FTIR. The ultrasound-responsive hydrogel materials are expected to possess a broad potential for applications in ultrasound diagnosis, imaging, and so on.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This research was supported by the National Key R&D Program of China (No. 2018YFC0114900), National Natural Science Foundation of China (Nos. 52103246, U1967217), Zhejiang Provincial Natural Science Foundation of China (Nos. LD22E050008, LD22A020002), China Postdoctoral Science Foundation (Nos. 2021TQ0341, 2020M671828), Ningbo Natural Science Foundation (Nos. 2021J203, 202003N4361), Youth Innovation Promotion Association of Chinese Academy of Sciences (No. 2019297), and Key Research Program of Frontier Science, Chinese Academy of Sciences (No. QYZDB-SSW-SLH036), the Sino-German Mobility Program (No. M-0424), K.C. Wong Education Foundation (No. GJTD-2019–13), National Independent Innovation Demonstration Zone Shanghai Zhangjiang Major Projects (No. ZJZX2020014), the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study (No. SN-ZJU-SIAS-003), Director Foundation of Ningbo Institute of Materials Technology and Engineering.

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2022.03.013.