Eu3+-Directed Supramolecular Metallogels with Reversible Quadruple-Stimuli Response Behaviors.

Smart luminescent materials that have the ability to reversibly adapt to external environmental stimuli and possess a wide range of responses are continually emerging, which place higher demands on the means of regulation and response sites. Here, europium ions (Eu3+)-directed supramolecular metallogels are constructed by orthogonal self-assembly of Eu3+ based coordination interactions and hydrogen bonding. A new organic ligand (L) is synthesized, consisting of crown ethers and two flexible amide bonds-linked 1,10-phenanthroline moieties to coordinate with Eu3+. Synergistic intermolecular hydrogen bonding in L and Eu3+-L coordination bonding enable Eu3+ and L to self-assemble into shape-persistent 3D coordination metallogels in MeOH solution. The key to success is the utilization of crown ethers, playing dual roles of acting both as building blocks to build L with C2-symmetrical structure, and as the ideal monomer for increasing the energy transfer from L to Eu3+'s excited state, thus maintaining the excellent luminescence of metallogels. Interestingly, such assemblies show K+, pH, F-, and mechano-induced reversible gel-sol transitions and tunable luminescence properties. Above findings are useful in the studies of molecular switches, dynamic assemblies, and smart luminescent materials.

Ligand Conformation Controls Assembly of a Helicate/Mesocate, Heteroleptic [Pd2L2L'2] Cages and a Six-Jagged [Pd6L12] Ring.

Molecular building blocks, capable of adopting several strongly deviating conformations, are of particular interest in the development of stimuli-responsive self-assemblies. The pronounced structural flexibility of a short acridone-based bridging ligand, equipped with two monodentate isoquinoline donors, is herein exploited to assemble a surprisingly diverse series of coordination-driven Pd(II) architectures. First, it can form a highly twisted Pd2L4 helicate, transformable into the corresponding mesocate, controlled by temperature, counter anion and choice of solvent. Second, it also allows the formation of heteroleptic cages, either from a mix of ligands with Pd(II) cations or by cage-to-cage transformation from homoleptic assemblies. Here, the acridone-based ligand tolerates counter ligands that carry their donors either in a diverging or converging arrangement, as it can rotate its own coordination sites by 90° and structurally adapt to both situations via shape complementarity. Third, by a near 180° rotation of only one of its arms, the ligand can adopt an S-shape conformation and form an unprecedented C6h-symmetric Pd6L12 saw-toothed six-membered ring.

Benzodifuranone Crystals with Solid-State Emission Arising from the Introduction of Bulky Substituents.

Benzodifuranone derivatives, structural analogues of widely studied diketopyrrolopyrrole, have been reported to show photoluminescence exclusively in solution states. Here, upon introducing bulky aromatic groups into benzodifuranone dyes, crystals with unprecedented solid-state emission were obtained. A crystallographic analysis revealed that the emissive properties should most likely be attributed to the absence of stacking between the dye scaffolds. In addition to the solid-state emission, the compound showed responsivity to external stimuli, i. e., luminescent mechanochromism and thermosalient effect.

Engineering Tunable Ratiometric Dual Emission in Single Emitter-based Amorphous Systems.

Molecular emitters with multi-emissive properties are in high demand in numerous fields, while these properties basically depend on specific molecular conformation and packing. For amorphous systems, special molecular arrangement is unnecessary, but it remains challenging to achieve such luminescent behaviors. Herein, we present a general strategy that takes advantage of molecular rigidity and S1 -T1 energy gap balance for emitter design, which enables fluorescence-phosphorescence dual-emission properties in various solid forms, whether crystalline or amorphous. Subsequently, the amorphism of the emitters based polymethyl methacrylate films endowed an in situ regulation of the dual-emissive characteristics. With the ratiometric regulation of phosphorescence by external stimuli and stable fluorescence as internal reference, highly controllable luminescent color tuning (yellow to blue including white emission) was achieved. There properties together with a persistent luminous behavior is of benefit for an irreplaceable set of optical information combination, featuring an ultrahigh-security anti-counterfeiting ability. Our research introduces a concept of eliminating the crystal-form and molecular-conformational dependence of complex luminescent properties through emitter molecular design. This has profound implications for the development of functional materials.

Hierarchical Dual-Mode Efficient Tunable Afterglow via J-Aggregates in Single-Phosphor-Doped Polymer.

The development of polymer-based persistent luminescence materials with color-tunable organic afterglow and multiple responses is highly desirable for applications in anti-counterfeiting, flexible displays, and data-storage. However, achieving efficient persistent luminescence from a single-phosphor system with multiple responses remains a challenging task. Herein, by doping 9H-pyrido[3,4-b]indole (PI2) into an amorphous polyacrylamide matrix, a hierarchical dual-mode emission system is developed, which exhibits color-tunable afterglow due to excitation-, temperature-, and humidity-dependence. Notably, the coexistence of the isolated state and J-aggregate state of the guest molecule not only provides an excitation-dependent afterglow color, but also leads to a hierarchical temperature-dependent afterglow color resulting from different thermally activated delayed fluorescence (TADF) and ultralong organic phosphorescence (UOP) behaviors of the isolated and aggregated states. The complex responsiveness based on the hierarchical dual-mode emission can serve for security features through inkjet printing and ink-writing. These findings may provide further insight into the regulated persistent luminescence by isolated and aggregated phosphors in doped polymer systems and expand the scope of stimuli-responsive organic afterglow materials for broader applications.

The current status of stimuli-responsive nanotechnologies on orthopedic titanium implant surfaces.

With the continuous innovation and breakthrough of nanomedical technology, stimuli-responsive nanotechnology has been gradually applied to the surface modification of titanium implants to achieve brilliant antibacterial activity and promoted osteogenesis. Regarding to the different physiological and pathological microenvironment around implants before and after surgery, these surface nanomodifications are designed to respond to different stimuli and environmental changes in a timely, efficient, and specific way/manner. Here, we focus on the materials related to stimuli-responsive nanotechnology on titanium implant surface modification, including metals and their compounds, polymer materials and other materials. In addition, the mechanism of different response types is introduced according to different activation stimuli, including magnetic, electrical, photic, radio frequency and ultrasonic stimuli, pH and enzymatic stimuli (the internal stimuli). Meanwhile, the associated functions, potential applications and developing prospect were discussion.

Multistage Self-Assembled Nanomaterials for Cancer Immunotherapy.

Advances in nanotechnology have brought innovations to cancer therapy. Nanoparticle-based anticancer drugs have achieved great success from bench to bedside. However, insufficient therapy efficacy due to various physiological barriers in the body remains a key challenge. To overcome these biological barriers and improve the therapeutic efficacy of cancers, multistage self-assembled nanomaterials with advantages of stimuli-responsiveness, programmable delivery, and immune modulations provide great opportunities. In this review, we describe the typical biological barriers for nanomedicines, discuss the recent achievements of multistage self-assembled nanomaterials for stimuli-responsive drug delivery, highlighting the programmable delivery nanomaterials, in situ transformable self-assembled nanomaterials, and immune-reprogramming nanomaterials. Ultimately, we perspective the future opportunities and challenges of multistage self-assembled nanomaterials for cancer immunotherapy.

Teaching an Old Compound New Tricks: Reversible Transamidation in Maleamic Acids.

Dynamic combinatorial chemistry is a method widely used for generating responsive libraries of compounds, with applications ranging from chemical biology to materials science. It relies on dynamic covalent bonds that are able to form in a reversible manner in mild conditions, and therefore requires the discovery of new types of these bonds in order to progress. Amides, due to their high stability, have been scarcely used in this field and typically require an external catalyst or harsh conditions for exchange. Compounds able to undergo uncatalysed transamidation at room temperature are still rare exceptions. In this work, we describe reversible amide formation and transamidation in a class of compounds known as maleamic acids. Due to the presence of a carboxylic acid in ß-position, these compounds are in equilibrium with their anhydride and amine precursors in organic solvents at room temperature. First, we show that this equilibrium is responsive to external stimuli: by alternating the additions of a Brønsted acid and a base, we can switch between amide and anhydride several times without side-reactions. Next, we prove that this equilibrium provides a pathway for reversible transamidation without any added catalyst, leading to thermodynamic distributions of amides at room temperature. Lastly, we use different preparation conditions and concentrations of Brønsted acid to access different library distributions, easily controlling the transition between kinetic and thermodynamic regimes. Our results show that maleamic acids can undergo transamidation in mild conditions in a reversible and tunable way, establishing them as a new addition to the toolbox of dynamic combinatorial chemistry.

Luminescent Organic-Inorganic Hybrid Metal Halides: An Emerging Class of Stimuli-Responsive Materials.

Luminescent organic-inorganic metal halides (OIMHs) are well known as a new materials family in recent years. Novel materials and applications of luminescent OIMHs have been explored by changing either the organic component or the metal halide species. Thereinto, the stimuli-responsive (SR) phenomena in OIMHs have drawn much attention recently, for not only their attractive application potential but also the helpfulness in understanding the stability of OIMHs to the external environment. Herein, the luminescent OIMHs that are sensitive to external stimuli including contact, pressure, mechanical grinding, light, heat, and gas molecules, are reviewed, with an emphasis on analyses of the structural change during the SR process. The applications of SR luminescent OIMHs in widespread fields, including gas sensing, information encryption, and rewritable luminescent paper are summarized. Finally, the challenges that deserve to be further explored in this research field are discussed, which provides certain guidance for the future study of SR luminescent OIMHs.

Small-Molecule Prodrug Nanoassemblies: An Emerging Nanoplatform for Anticancer Drug Delivery.

The antitumor efficiency and clinical translation of traditional nanomedicines is mainly restricted by low drug loading, complex preparation technology, and potential toxicity caused by the overused carrier materials. In recent decades, small-molecule prodrug nanoassemblies (SMP-NAs), which are formed by the self-assembly of prodrugs themselves, have been widely investigated with distinct advantages of ultrahigh drug-loading and negligible excipients-trigged adverse reaction. Benefited from the simple preparation process, SMP-NAs are widely used for chemotherapy, phototherapy, immunotherapy, and tumor diagnosis. In addition, combination therapy based on the accurate co-delivery behavior of SMP-NAs can effectively address the challenges of tumor heterogeneity and multidrug resistance. Recent trends in SMP-NAs are outlined, and the corresponding self-assembly mechanisms are discussed in detail. Besides, the smart stimuli-responsive SMP-NAs and the combination therapy based on SMP-NAs are summarized, with special emphasis on the structure-function relationships. Finally, the outlooks and potential challenges of SMP-NAs in cancer therapy are highlighted.

Multifunctional Features of Organic Charge-Transfer Complexes: Advances and Perspectives.

The recent progress of charge-transfer complexes (CTCs) for application in many fields, such as charge transport, light emission, nonlinear optics, photoelectric conversion, and external stimuli response, makes them promising candidates for practical utility in pharmaceuticals, electronics, photonics, luminescence, sensors, molecular electronics and so on. Multicomponent CTCs have been gradually designed and prepared as novel organic active semiconductors with ideal performance and stability compared to single components. In this review, we mainly focus on the recently reported development of various charge-transfer complexes and their performance in field-effect transistors, light-emitting devices, lasers, sensors, and stimuli-responsive behaviors.

Supramolecular Control on the Optical Properties of a Dye-Polyelectrolyte Assembly.

Control of fluorescent molecular assemblies is an exciting area of research with large potential for various important applications, such as, fluorescence sensing/probing, cell imaging and monitoring drug-delivery. In the present contribution, we have demonstrated control on the extent of aggregation of a dye-polyelectrolyte assembly using a macrocyclic host molecule, sulfobutylether-ß-cyclodextrin (SBE-ß-CD). Initially, a cationic molecular rotor based organic dye, Auramine-O (AuO), undergoes aggregation in the presence of an anionic polyelectrolyte, polystyrene sulfonate (PSS), and displays a broad intense new emission band along with large variation in its absorption features and excited-state lifetime. A manipulation of the monomer-aggregate equilibrium of the dye-polyelectrolyte assembly has been achieved by introducing a cyclodextrin based supramolecular host, SBE-ß-CD, which leads to relocation of AuO molecules from polyelectrolyte (PSS) to supramolecular host cavity, owing to the formation of a host-guest complex between AuO and SBE-ß-CD. A reversible control on this manipulation of monomer-aggregate equilibrium is further achieved by introducing a competitive guest for the host cavity i. e., 1-Adamantanol. Thus, we have demonstrated an interesting control on the dye-polyelectrolyte aggregate assembly using a supramolecular host molecule which open up exciting possibilities to construct responsive materials using a repertoire of various host-specific guest molecules.

Paclitaxel-loaded and folic acid-modified PLGA nanomedicine with glutathione response for the treatment of lung cancer.

Targeted delivery and smart response of nanomedicine hold great promise for improving the therapeutic efficacy and alleviating the side effects of chemotherapy agents in cancer treatment. However, availability of only a few studies that discuss organic nanomedicines with these properties limits the development prospects of nanomedicines. In the present study, folic acid (FA)-targeted delivery and glutathione (GSH) smart responsive nanomedicine were rationally designed for paclitaxel (PTX) delivery for the treatment of lung cancer. Compared with other stimuli-responsive nanomedicines, this nanocarrier was not only sensitive to biologically relevant GSH for on-demand drug release but also biodegradable into biocompatible products after fulfilling its delivery task. The nanomedicine first entered tumor cells via FA and its receptor-mediated endocytosis. After the lysosomal escape, poly(lactic-co-glycolic acid) (PLGA) nanomedicine was triggered by a higher level of GSH and released its cargo into the tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells significantly but also possessed less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the potential of a multifunctional nano-platform to enhance bioavailability and reduce the side effects of chemotherapy agents.

Dual-stimuli-responsive porous polymer enzyme reactor for tuning enzymolysis efficiency.

A strategy for preparing a dual-stimuli-responsive porous polymer membrane enzyme reactor (D-PPMER) is described, consisting of poly (styrene-maleic anhydride-N-isopropylacrylamide-acrylate-3',3'-dimethyl-6-nitro-spiro[2H-1-benzopyran-2,2'-indoline]-1'-esterspiropyran ester) [P(S-M-N-SP)] and D-amino acid oxidase. Tunable control via "on/off" 365 nm UV light irradiation and temperature variation was used to change the membrane surface configuration and adjust the enzymolysis efficiency of the D-PPMER. A chiral capillary electrophoresis technique was developed for evaluation of the enzymatic efficiency of D-PPMER with a Zn(II)-dipeptide complex as the chiral selector and D,L-serine as the substrate. Interestingly, the enzymatic kinetic reaction rate of D-PPMER under UV irradiation at 36 °C (9.2 × 10-2 mM·min-1) was 3.2-fold greater than that of the free enzyme (2.9 × 10-2 mM·min-1). This was because upon UV irradiation at high temperature, the P(SP) and P(N) moieties altered from a "stretched" to a "curled" state to encapsulate the enzyme in smaller cavities. The confinement effect of the cavities further improved the enzymatic efficiency of the D-PPMER. This protocol highlights the outstanding potential of smart polymers, enables tunable control over the kinetic rates of stimuli-responsive enzyme reactors, and establishes a platform for adjusting enzymolysis efficiency using two different stimuli.

Luminescent Behavior Elucidation of a Disilane-Bridged D-A-D Triad Composed of Phenothiazine and Thienopyrazine.

A σ-π extended aryldisilane, comprising a thienopyrazine group as an acceptor fragment and phenothiazine groups as the donor moiety, has been prepared through the introduction of two Si-Si bridges (compound 1). X-ray diffraction analysis determined the crystal structure of 1, and experimental and theoretical approaches investigated its optical properties. Solvatochromic studies revealed the dual emission of 1 in all solvents tested. Compound 1 also exhibited fluorescence in the solid state upon excitation with a hand-held UV lamp, as well as mechanochromic luminescent properties. The packing mode in the crystal structure, variation of phenothiazine conformation, morphological changes between crystalline and amorphous phases are the major factors showing reversible fluorescence under external stimuli. A theoretical conformer study found that 1 exists in distinct conformational groups differing in Gibbs free energy by less than 3 kcal mol-1 . The conformer in the crystalline state of 1 can promote the complete separation of the HOMO and LUMO between the phenothiazine donor and the thienopyrazine acceptor, linked by the disilane linker. HOMO-LUMO energy transition in the crystalline state is forbidden due to the lack of frontier orbital overlap. Crystalline state emission showed LUMO → HOMO-1 transition (locally excited (LE) state). In the amorphous state, the partial presence of quasi-axial conformers allows intramolecular charge-transfer type emission via energy transfer from dominant quasi-equatorial conformers. The strategy proposed in this work provides important guidance for developing stimuli-responsive materials with controlled excited states.

A Hierarchical Peptide-Lanthanide Framework To Accurately Redress Intracellular Carcinogenic Protein-Protein Interaction.

Intracellular protein-protein interactions (PPIs) are a vital and yet underexploited class of therapeutic targets for their crucial roles in cellular processes and involvement in disease initiation and progression. Although some successful chemistry and nanotechnologies have been introduced into peptide PPI modulators to allow cell and tissue permeability, significant challenges remain with regard to the efficient and precise modulation of PPIs within specific cells of diseased tissues, such as solid tumors. Herein, an intratumoral transformable hierarchical framework, termed iPLF, was fabricated via a two-step self-assembly between peptides and lanthanide-doped nanocrystals. In this proof-of-concept study, using NanoEL effect, TME response, and tumor marker targeting, iPLF in vivo delivered the p53-MDM2 modulator DPMI into tumor cells and ß-catenin-Bcl9 modulator Bcl9p into tumor stem cells. This crafted programmed nanomedicine with triple-stage delivery and responsiveness accurately modulated the specific intracellular protein-protein interactions, resulting in the suppression of tumor growth and metastasis in vivo, while maintaining a highly favorable safety profile. iPLF reached the goal of accurate, potent, and hazard-free intracellular PPI modulation, thereby providing a means to improve current knowledge of PPI networks and a novel therapeutic strategy for a great variety of diseases.

Formation and Out-of-Equilibrium, High/Low State Switching of a Nitroaldol Dynamer in Neutral Aqueous Media.

The nitroaldol reaction is demonstrated as an efficient dynamic covalent reaction in phosphate buffers at neutral pH. Rapid equilibration was recorded with pyridine-based aldehydes, and dynamic oligomerization could be achieved, leading to nitroaldol dynamers of up to 17 repeating units. The dynamers were applied in a coherent stimuli-responsive molecular system in which larger dynamers transiently existed out-of-equilibrium in a neutral aqueous system rich in formaldehyde, controlled by nitromethane.

Stimuli-Responsive Molecular Photon Upconversion.

The addition of stimuli-responsiveness to anti-Stokes emission provides a unique platform for biosensing and chemosensing. Particularly, stimuli-responsive photon upconversion based on triplet-triplet annihilation (TTA-UC) is promising due to its occurrence at low excitation intensity with high efficiency. This Minireview summarizes the recent developments of TTA-UC switching by external stimuli such as temperature, oxygen, chemicals, light, electric field, and mechanical force. For the systematic understanding of the underlying general mechanisms, the switching mechanisms are categorized into four types: 1) aggregation-induced UC; 2) assembly-induced air-stable UC; 3) diffusion-controlled UC; and 4) energy-transfer-controlled UC. The development of stimuli-responsive smart TTA-UC systems would enable sensing with unprecedented sensitivity and selectivity, and expand the scope of TTA-UC photochemistry by combination with supramolecular chemistry, materials chemistry, mechanochemistry, and biochemistry.

Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice.

Many novel vaginal/rectal microbicide formulations failed clinically due to safety concerns, indicating the need for the early investigation of lead microbicide formulations. In this study, the preclinical safety of an HIV-1 gp120 and mannose responsive microbicide delivery system (MRP) is evaluated in C57BL/6 mice. MRP was engineered through the layer-by-layer coating of calcium carbonate (CaCO3) with Canavalia ensiformis lectin (Con A) and glycogen. MRP mean particle diameter and zeta potential were 857.8 ± 93.1 nm and 2.37 ± 4.12 mV, respectively. Tenofovir (TFV) encapsulation and loading efficiencies in MRP were 70.1% and 16.3% w/w, respectively. When exposed to HIV-1 rgp120 (25 µg/mL), MRP released a significant amount of TFV (∼5-fold higher) in vaginal and seminal fluid mixture compared to the control (pre-exposure) level (∼59 µg/mL) in vaginal fluid alone. Unlike the positive control treated groups (e.g., nonoxynol-9), no significant histological damages and CD45+ cells infiltration were observed in the vaginal and major reproductive organ epithelial layers. This was probably due to MRP biocompatibility and its isosmolality (304.33 ± 0.58 mOsm/kg). Furthermore, compared to negative controls, there was no statistically significant increase in pro-inflammatory cytokines such as IL1α, Ilß, IL7, IP10, and TNFα. Collectively, these data suggest that MRP is a relatively safe nanotemplate for HIV-1 gp120 stimuli responsive vaginal microbicide delivery system.

Room-Temperature Phosphorescence in Pure Organic Materials: Halogen Bonding Switching Effects.

Organic room-temperature phosphorescence (ORTP), when combined with external stimuli-responsive capability, is very attractive for sensors and bio-imaging devices, but remains challenging. Herein, by doping two ß-iminoenamine-BF2 derivatives (S-2CN and S-2I) into a 4-iodoaniline (I-Ph-NH2 ) crystalline matrix, the formation of S-2CN⋅⋅⋅I-Ph-NH2 and S-2I⋅⋅⋅I-Ph-NH2 halogen bonds leads to bright-red RTP emissions from these two host-guest doped crystals (hgDCs) with quantum efficiencies up to 13.43 % and 15.96 %, respectively. Upon treatment with HCl, the competition of I-Ph-NH2 ⋅HCl formation against S-2I⋅⋅⋅I-Ph-NH2 halogen bonding switches off the red RTP from S-2I/I-Ph-NH2 hgDCs, whereas the stable halogen-bonded S-2CN⋅⋅⋅I-Ph-NH2 ensures red RTP from S-2CN/I-Ph-NH2 hgDCs remains unchanged. A security protection luminescence pattern by using these different HCl-responsive RTP behaviors was designed.