Graphene
Environmentally Responsive Graphene Systems Jing Zhang, Long Song, Zhipan Zhang,* Nan Chen, and Liangti Qu*
From the Contents 1. Introduction ........................................ 2152
Graphene materials have been attracting significant research
interest in the past few years, with the recent focuses on graphene-based electronic devices and smart stimulusresponsive systems that have a certain degree of automatism. 3. Conclusion .......................................... 2162 Owing to its huge specific surface area, large room-temperature electron mobility, excellent mechanical flexibility, exceptionally high thermal conductivity and environmental stability, graphene is identified as a beneficial additive or an effective responding component by itself to improve the conductivity, flexibility, mechanical strength and/or the overall responsive performance of smart systems. In this review article, we aim to present the recent advances in graphene systems that are of spontaneous responses to external stimulations, such as environmental variation in pH, temperature, electric current, light, moisture and even gas ambient. These smart stimulusresponsive graphene systems are believed to have great theoretical and practical interests to a wide range of device applications including actuators, switches, robots, sensors, drug/ gene deliveries, etc. 2. Stimulus-Responsive Graphene Systems .............................................. 2152
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1. Introduction This year celebrates the 10th anniversary of graphene's debut from the mechanical cleavage of graphite.[1] As an ideal two-dimensional (2D) sheet of sp2-hybridized carbon material, graphene is actually the basic building block of other dimensional carbon materials such as fullerenes and carbon nanotubes. More importantly, this unique structure is well associated with graphene's large specific surface area, excellent mechanical property,[2] high room-temperature intrinsic electron mobility[3–5] and thermal conductivity,[6] making graphene a “star” material that has attracted enormous attentions in a wide range of areas including energy conversion and storage materials,[7–11] electronic devices,[12–14] sensors,[15–20] biological materials,[21] catalysis,[22] etc. With the one-decade ongoing research efforts devoted to this marvelous material, the focus of the chemical scientists has moved by and by from the pure chemical synthesis of graphene to the controlled construction of ordered graphene nano/macro structures and designated applications of graphene in different advanced systems. In particular, smart systems that can spontaneously respond to environmental changes, such as pH, temperature, electrical, light and other stimuli, are of great theoretical and practical interests, as they work to mimic living organisms and could be used for diverse applications ranging from actuators, robots to sensors. Owing to the above-mentioned excellent electrical, thermal and mechanical properties, graphene has been recognized as an effective additive or an active component by itself to boost the performance of these smart systems. In this review, we will discuss the recent development, contributed by us and other groups, in the stimulus-responsive graphene systems under various environmental stimuli, and present the potential trend in the future direction of this fast-growing research field. Since graphene can play either a passive role as a mere platform to provide conductivity/mechanical support or an active role as the stimulus-sensitive responsor by itself in the individual systems, the current review is thus structured to reflect this distinct difference in graphene's functionality.
2. Stimulus-Responsive Graphene Systems 2.1. Graphene as a Passive Platform/Supporting Substrate As graphene has excellent electrical, mechanical and thermal properties, it can function as an effective working platform to boost the important characteristics such as conductivity, robustness and sensitivity in different stimulus-responsive systems. Wang and coworkers prepared three-dimensional (3D) graphene assemblies from graphene oxide (GO) by a convenient in situ reduction with a combination of oxalic acid and sodium iodide.[23] The obtained 3D graphene network was shown to be an electrically conductive platform to infiltrate polydimethylsiloxane (PDMS) as an organicsolvent-sensing device to distinguish solvents with different polarity. In principle, PDMS exhibits a swelling process that is dependent on the polarity of various organic solvents, and the swelling of PDMS in turn blocks some of electrical
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conduction paths through the composite material, resulting in an increase in the overall resistance of the composite material. As shown in Figure 1a, when the composite was under a constant potential of 0.01 V, an environmental stimulus such as a droplet of a solvent on its surface led to the decrease of the current signal through the PDMS/graphene composite due to the fast swelling of the PDMS within several seconds. The current could return to its original value after the evaporation of the solvent, and the variation in the current was found to be in line with the relative polarity of the solvent (the relative polarity of ethanol, acetone, and chloroform are 0.654, 0.355, and 0.259, respectively), realizing a smart system responsive to environmental solvent polarity. Zhang et al. mixed 10,12-pentacosadiynoicacid as a diacetylene (DA) monomer and polymethylmethacrylate (PMMA) with graphene and then photopolymerized DA to form the PDA–PMMA/graphene composite as a one-shot electric current sensing material.[24] As illustrated in Figure 1b, the PDA–PMMA/graphene composite underwent an irreversible blue–red phase transition upon an externally applied current, where the addition of PMMA in the composite made the color transition more conspicuous, and the critical responsive current of this color change was found to be linearly dependant on the graphene content. The phenomenon was rationalized by the reduction of effective conjugation length induced by the conformation change of PDA backbone upon electrical stimulation. As the very thin PDA layer had strong interaction with the graphene via the hydrogen-bond interaction, the critical electrical stimulus required to initiate the conformation change of PDA was therefore directly related to the graphene content, rendering the possibility to use this material as an indicator in certain overcurrent protection circuits with different critical currents. Recently, we have devised several graphene systems that responded to the magnetic stimulus in the environment. Magnetic Fe3O4 nanoparticles were selected as the active working component to be embedded in graphene quantum dot assembled microspheres (GQDSs)[25] and one-dimensional (1D) graphene fibers (GFs),[26] enabling them to move or bend under the applied magnetic field as the response (Figure 1c,d). Additionally, a 3D graphene–Fe3O4 nanocomposite was synthesized by simple hydrothermal grafting reaction to exploit the low-density, high specific surface area of 3D graphene framework and the distinctive microwaveabsorbing ability of Fe3O4.[27] As graphene provided a large contact surface for individual dispersion of well-adhered Dr. J. Zhang,[+] L. Song,[+] Prof. Z. Zhang, Dr. N. Chen, Prof. L. Qu Key Laboratory of Cluster Science Ministry of Education of China Beijing Key Laboratory of Photoelectronic/ Electrophotonic Conversion Materials School of Chemistry Beijing Institute of Technology Beijing, 100081, P. R. China E-mail: [email protected]; [email protected] [+] J. Z. and L. S. contributed equally to the work DOI: 10.1002/smll.201303080
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Fe3O4 particles and acted as an excellent substrate for the absorption of microwave that involved both dielectric loss and magnetic loss, the electromagnetic wave absorption characteristics of graphene–Fe3O4 nanocomposite were much better than that of the pure graphene and Fe3O4. For a graphene–Fe3O4 composite film with a thickness of 3 mm, the deep reflection loss reached -23.0 dB at about 11.5 GHz with a broad wave absorbing area of a reflection loss higher than -10 dB (90% of signal attenuation) in the frequency range of 9.2–15.0 GHz, demonstrating its good microwave absorbing ability in both low- and high- frequency bands. With its reasonable biocompatibility, graphene can also work as an effective platform for sensing changes in the biological environment. For instance, GO was shown to bind and quencher a single-stranded DNA (ssDNA) through unique DNA/GO interactions.[28] On the basis of this phenomenon, Fan and coworkers designed a graphene nanoprobe for fast and sensitive multicolor fluorescent DNA analysis.[29] As shown in Figure 2a, the fluorescence of the ssDNA probe (P1) tagged by FAM (carboxyfluorescein) was almost quantitatively quenched by GO, while it rested largely unchanged even in the presence of GO if P1 formed a duplex with its complementary target T1, suggesting the establishment of a sensing platform for quantitative DNA analysis. Theoretical simulations indicated ssDNA was strongly interacted with GO through the π-stacking interaction between the ring structures in its nucleobases and the conjugated units of the graphene, but in contrast, the double-stranded DNA (dsDNA) was not stably adsorbed on GO and retained its helical structure due to the shield of its nucleobases within the densely negatively charged phosphate backbone. Li et al. further demonstrated a more complex system that GO not only worked as fluorescence quencher but also as the transporter to deliver DNA into living cells.[30] As illustrated in Figure 2b, the nanomachine was
Zhipan Zhang received his doctorate degree from École Polytechnique Fédérale de Lausanne in 2008. After working at Dyesol Ltd, Monash University and the University of Calgary, he is now an Associate Professor at Beijing Institute of Technology. His research focuses on energy-related applications of new materials, particularly in photovoltaics and solar fuels.
Liangti Qu received a Ph.D. in Chemistry from Tsinghua University (Beijing, China) in 2004. He is now a Professor of Chemistry at the Beijing Institute of Technology and leads the nanocarbon research group. His research interests in materials chemistry mainly focus on the synthesis, functionalization and application of nanomaterials with carbon–carbon conjugated structures, including carbon nanotubes, graphene and conducting polymers.
based on the principal that triplex-forming oligonucleotide exhibited duplex–triplex transition at basic–acid conditions and the difference in the affinity of GO with ssDNA and triplex DNA would lead to sharp changes in the fluorescence signal of the nucleic acid. As GO was able to move across the cell membrane to fulfill intracellular delivery, this process could be used in probing pH changes during apoptosis in
Figure 1. (a) The real-time change of the current passing through the graphene–PDMS composite when solvents of ethanol, acetone, and chloroform were applied onto its surface. The applied potential was fixed at 0.01 V. Arrows indicated the application of organic solvents droplets on the surface composite (Reproduced with permission.[23] Copyright 2012 Royal Society of Chemistry). (b) Photographs under ambient light and images from fluorescent microscope for the PDA-PMMA/graphene composite before and after current stimulus (Reproduced with permission.[24] Copyright 2013, American Chemical Society). (c) The suspension of Fe3O4–GQDSs in petroleum ether and the magnetic separation of Fe3O4–GQDSs from petroleum ether under an external magnet (Reproduced with permission.[25] Copyright 2012, IOP Publishing Ltd). (d) The straight Fe3O4/graphene fiber and its response to the attraction of the magnet (Reproduced with permission.[26] Copyright 2012, Wiley-VCH). small 2014, 10, No. 11, 2151–2164
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Figure 2. (a) Scheme for the GO-based multicolor DNA analysis. Fluorescence spectra of mixture probes (P5, P6, P7) in the presence of different targets T5 (blue), T6 (red) and T7 (orange) with the excitation wavelengths of 494, 643, and 587 nm (Reproduced with permission.[29] Copyright 2010, Wiley-VCH). (b) Schematic illustration of the working principle of the duplex–triplex/GO nanocomplex. (Reproduced with permission.[30] Copyright 2013, Springer Verlag).
living Ramos cells where the initially quenched fluorescence of the nucleic acid significantly recovered with the decrease of pH induced by the acidification of vincristine sulfate.
2.2. Graphene/Polymer Composites for pH and Temperature Sensitive Systems As graphene can be chemically modified and facilely functionalized, it has been adopted into various stimuli-responsive
polymers for different applications. Fang et al. selected chitosan as a mediating agent to stabilize GO in the solution and then converted GO into reduced GO (rGO) through chemical reduction where rGO and chitosan could be noncovalently bonded through the amino and hydroxyl groups of chitosan via zwitterionic interaction and hydrogen bonding.[31] As shown in Figure 3a, the suspension of rGO/ chitosan was pH responsive and it changed from a homogenous solution to a cloudy one as the pH increased from below 6 to above 8, with its transmittance increased from
Figure 3. (a) Left, transmittance of the supernatants of rGO/chitosan suspensions with different pH values after sedimentations. Right, schematic illustration of the reversible changes of the rGO/chitosan in aqueous media with pH as a stimulus (Reproduced with permission.[31] Copyright 2010 American Chemical Society). (b) Photographs of chitosan-functionalized rGO aqueous solutions with different pH values from 2.0 to 12.0 (Reproduced with permission.[32] Copyright 2012, Elsevier B.V.).
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Figure 4. (a) Schematic illustration of the GO–block polymer composite and its application as a thermal sensor. (b) Reversibility test of the on–off switching behavior in terms of PL quenching (Reproduced with permission.[35] Copyright 2013 Royal Society of Chemistry). (c) Upper, synthesis of AucorePtshell nanoparticles on graphene sheets by a galvanic replacement strategy and later attachment of the dextran-based smart polymer with thiol-ends. Lower, the photos and sketch maps of the hybrid catalyst in water below/above LCST (Reproduced with permission.[38] Copyright 2013, Royal Society of Chemistry).
about 20–80% after sedimentation in the meantime. This was rationalized by a chitosan-conformation induced rGO aggregation process. Chitosan was known to be pH-responsive with highly extended molecular chains at low pH, while at higher pH values, its deprotonation to form intermolecular associates through hydrogen bonding induced the aggregation of rGO (Figure 3a right), validating a reversible pHresponsive graphene system. Liu et al. further developed this system and obtained stable dispersion of chitosan-functionalized rGO at pH values of over 9, where the ionization of graphene mainly dominated the surface charge of the composite and led to a stable dispersion (Figure 3b).[32] They found that the increase of the chitosan coverage and cross-linking in the system resulted in dispersion only in acidic solution but not in neutral and basic solutions as shown in ref. [[31]], due to the strong electrostatic shielding effect of cross-linked chitosan on rGO. Differently, Lee and coworkers grafted poly(acrylic acid) (PAA) brushes on functionalized GO via surface-initiated atom transfer radical polymerization (SI-ATRP) and a subsequent hydrolysis reaction to obtain aqueous dispersion of graphene nanocomposites with pH-tunability.[33] The GO– PAA composite tended to aggregate at pH = 1 but remained dispersed at pH = 5 and 9, owing to the reversible conformational changes of PAA macromolecules between the collapsed and extended states at different pH values. Ren et al. also reported a pH responsive graphene–polyacrylamide (G– PAM) system that precipitated at low pH of 2.9 but dispersed homogeneously in water at pH higher than 4.[34] Interestingly, PAM molecules were known to have no pH responsive property, and therefore, this pH response was attributed to the possible hydrolyzation of PAM side chains (–CONH2) into acrylate during the reduction of GO to form G–PAM. When a thermally sensitive polymer such as poly(N-isopropylacrylamide) (PNIPAM) was incorporated, graphene small 2014, 10, No. 11, 2151–2164
systems could be temperature-responsive. Yang et al. constructed a GO-based temperature sensing platform by functionalizing GO with P7AC-b-PNIPAM-b-PSN3 triblock copolymers that were composed of poly(7-(4-(acryloyloxy) butoxy)coumarin) (P7AC) as the fluorescent component, PNIPAM as the thermally responsive polymer, and a short poly(azidostyrene) (PSN3) block as covalently binding unit to the GO surface (Figure 4a).[35] When the temperature of the solution was higher than 32 °C, the lower critical solution temperature (LCST) of PNIPAM, the photoluminescence (PL) of GO–block polymer composite decreased dramatically while the PL of pristine block polymer remained unchanged. This was understood by the changes of the conformation of PNIPAM with the temperature. As PNIPAM became hydrophobic with the condensed chain conformation in water above its LCST, the inter-space between the P7AC and the GO surface decreased, thus facilitating an efficient Förster resonance energy transfer (FRET) between the blue-emitting coumarins in the P7AC block and GO that quenched the PL. As is shown in Figure 4b, the quenched fluorescence could be fully recovered upon cooling the solution to a temperature below LCST and the system could be continuously cycled between the PL on–off states, owing to the reversible conformation changes of PNIPAM chains between the condensed and extended states with the temperature variation. In a different approach, Fan et al. prepared grafted PNIPAM onto GO by in situ free-radical polymerization and found that the conformation change of PNIPAM with the temperature led to unique crumpling feature of GO–PNIPAM hybrids when dried above LCST.[36] They further demonstrated that modifying graphene with PNIPAM-grafted dextran (DexPNI) could also induce graphene’s sensitivity to external temperature variations. When the temperature of a clear DexPNI–GO dispersion was
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increased from 25 °C to 40 °C, DexPNI–GO content totally precipitated and the solution became nearly transparent. When the heated suspension was cooled back to 25 °C, the dispersity of DexPNI–GO could be facilely recovered by gentle shaking, showing reversible temperature-induced aggregation/dispersion behaviors of DexPNI–NGO.[37] Interesting, the same group designed a smart catalytic system with temperature responsive catalytic behaviors by covalently linking a dextran-based PNIPAM polymer with thiol-ends to AucorePtshell bimetallic nanoparticles supported by the graphene (G–Au@Pt) (Figure 4c).[38] When the system was used in the catalytic reduction of 4-nitrophenol by NaBH4, the apparent pseudo-first-order rate constant, kapp, was found to increase linearly in the temperature range of 15–30 °C, in line with the well-known Arrhenius law, but decreased significantly when the temperature reached 35 °C (higher than the LCST of PNIPAM). The PNIPAM chains underwent the hydrophilic to hydrophobic phase transition between 30 and 35 °C and induced a macroscopic agglomeration and precipitation of the catalyst (photos in Figure 4c), therefore resulting in a complete shielding of the catalytically active sites of Au@ Pt nanoparticles and the decreased kapp. It should be further noted that it is possible to have graphene–polymer systems responsive simultaneously to pH and temperature if a pH sensitive block such as acrylic acid (AA) is introduced into the polymer backbone. Sun et al. synthesized GO interpenetrating PNIPAM-AA hydrogel networks by connecting GO sheets and PNIPAM-co-AA microgels with covalent bonds, where the GO/PNIPAM-AA showed a reversible shape change upon heating/cooling between 20 and 50 °C and a pH dependence of volume phase transition temperature (VPTT).[39] Similarly, Ye and coworkers built a pH- and temperature-responsive PNIPAM/AA/GO double network (DN) hydrogel via a two-step sequential free-radical polymerization.[40] The introduction of GO in the DN hydrogel
was found to effectively decrease the VPTT of the PNIPAM/ PAA hydrogel from approximately 32 °C to around 29 °C and increase the response rate of the DN hydrogel, which were rationally attributed to the high thermal conductivity of graphene. As a result, GO containing DN hydrogels had a fast response to pH/temperature variation and swelled as the temperature changed from 35 °C to 20 °C or the pH varied from 4 to approximately 8, proving the concept of graphene systems responsive dually to pH and temperature stimuli. The establishment of smart graphene systems that spontaneously respond to environmental stimuli renders the possibility to construct intracellular carrier for drug deliveries, such as anticancer drugs doxorubicin (DOX) and camptothecin (CPT). Li and coworkers prepared a graphene hybrid by the simultaneous reduction of GO and assembly of Pluronic F127 (PF127) and rGO.[41] The amphiphilic nature of PF127 helped the dispersion of rGO in physiological environment, with the hydrophobic segments of PF127 anchoring at the surface of graphene via hydrophobic interaction while the hydrophilic chains of PF127 extending to the solution. Impressively, the loading efficiency of the PF127/rGO hybrid for DOX could reach 289% (w/w) due to the strong interaction of π–π stacking, and the release of DOX was faster in acidic media than in neutral and basic media as a trade-off between the change of hydrogen bonding and different solubility of DOX at different pH values. The same group further designed an engineered redox-responsive graphene system, NGO–SS–mPEG, composed of nano-GO (NGO) sheets with a sheddable methoxy-polyethylene-glycol (mPEG) shell attached via a disulfide linkage (Figure 5a).[42] Similar to PF127, the mPEG moiety stabilized NGO in the physiological environment, thus facilitating the loading and releasing of the drug doxorubicin hydrochloride (DXR). Meanwhile, the disulfide linkage was inclined to undergo rapid cleavage through exchange reaction of thiol ligands induced by the
Figure 5. Schematic diagram showing antitumor activity of redox-sensitive DXR-loaded NGO-SS-mPEG. (a) PEG-shielded NGO with disulfide linkage for prolonged blood circulation. (b) Endocytosis of NGO-SS-mPEG in tumor cells via the EPR effect. (c) GSH trigger (GSH > fourfold relative to normal cells) resulting in PEG detachment. (d) Rapid drug release on the tumor site (Reproduced with permission.[44] Copyright 2011, Wiley-VCH).
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difference between extracellular and intracellular glutathione (GSH) concentrations in some tumor cells. Cell proliferation assays with HeLa cells clearly demonstrated the pharmacological efficacy of DXR released from NGO–SS– mPEG in the presence of enhanced GSH concentrations, verifying the GSH-triggered intracellular release of DXR for antitumor activities. In a similar work, AlNahain et al. used a thiol grafted Pluronic (PLU–SH) to form disulfide bonds surrounded rGO/PEG matrix, achieving up to around 35% higher DOX loading efficiency together with the controlled release of DOX triggered by GSH and pH.[43] Besides redox and pH stimuli, thermal stimulus could potentially initiate the drug delivery in graphene systems containing thermo-responsive PNIPAM as well. Pan et al. grafted PNIPAM onto GO sheets via click chemistry and used PNIPAM–GO as the carrier for CPT through hydrophobic interactions and π–π stacking.[44] The Figure 6. (a) Optical microscope images of GO/TiO2 nanocomposite (15 wt% particle PNIPAM–GO loaded CPT up to 15.6 wt% concentration) based ER fluid without an electric field (left) and with an electric field (right) and demonstrated a stable and continuous (Reproduced with permission.[45] Copyright 2011 Royal Society of Chemistry). (b) Photographs drug release during the in vitro test, with of the GO sheet-based ER fluid prepared by centrifugation of dispersion of GO sheets in (c) Extrusion of the GO sheet-based a potency of a 20% growth inhibition at ethanol (upper phase) and silicone oil (lower phase). [47 ER fluid from a needle (Reproduced with permission. ] Copyright 2012, Royal Society of −6 M. Unfortua concentration of 1 × 10 Chemistry). nately, no temperature-dependant drug releasing kinetics were studied in the work, demanding addi- and coworkers employed a solvent-exchange approach to tional efforts to explore the possibility to thermally control prepare easily-processed, GO-based ER fluids with isolated GO sheets (Figure 6b,c).[47] Due to the minimization of π-π the release of CPT from the graphene matrix. interaction between GO sheets and the electrostatic repulsion between oxygen functional groups, solvent-exchanged 2.3. Electro-Responsive Graphene Systems GO sheets had a settling velocity about 1600 times slower than that of conventional mechanically ground GO sheets, 2.3.1. Electrorheology thus forming no sediment after ninety days. Compared Electrorheological (ER) materials are usually suspensions to the ER efficiency of 67% at a shear rate of 100 s−1 for of polarizable dielectric or semiconducting tiny particles in mechanically ground GO, the solvent exchanged GO insulating oils. They are capable of reversibly changing from sheets demonstrated a tripled ER efficiency of 207%, posa Newtonian fluid state to a fibrillar solid-like state under sibly because its higher surface area provided sufficient the application of an external electric field. Choi and cow- electrostatic interaction to counteract the hydrodynamic orkers decorated GO with TiO2 nanoparticles by a nega- inter-action under shear flow. They further decorated GO tive–positive electrostatic attraction method and studied sheets with TiO2 nanorods and reported an ER efficiency the ER property of the hybrid material.[45] As shown in of 554% at a shear rate of 100 s−1.[48] Meanwhile, the GO/ Figure 6a, when the ER fluid was placed between two par- TiO2 nanorods composite even showed electro-responsive allel electrodes separated at 300 μm under an electric field, performance in an extremely low concentration of
Environmentally Responsive Graphene Systems Jing Zhang, Long Song, Zhipan Zhang,* Nan Chen, and Liangti Qu*
From the Contents 1. Introduction ........................................ 2152
Graphene materials have been attracting significant research
interest in the past few years, with the recent focuses on graphene-based electronic devices and smart stimulusresponsive systems that have a certain degree of automatism. 3. Conclusion .......................................... 2162 Owing to its huge specific surface area, large room-temperature electron mobility, excellent mechanical flexibility, exceptionally high thermal conductivity and environmental stability, graphene is identified as a beneficial additive or an effective responding component by itself to improve the conductivity, flexibility, mechanical strength and/or the overall responsive performance of smart systems. In this review article, we aim to present the recent advances in graphene systems that are of spontaneous responses to external stimulations, such as environmental variation in pH, temperature, electric current, light, moisture and even gas ambient. These smart stimulusresponsive graphene systems are believed to have great theoretical and practical interests to a wide range of device applications including actuators, switches, robots, sensors, drug/ gene deliveries, etc. 2. Stimulus-Responsive Graphene Systems .............................................. 2152
small 2014, 10, No. 11, 2151–2164
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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J. Zhang et al.
1. Introduction This year celebrates the 10th anniversary of graphene's debut from the mechanical cleavage of graphite.[1] As an ideal two-dimensional (2D) sheet of sp2-hybridized carbon material, graphene is actually the basic building block of other dimensional carbon materials such as fullerenes and carbon nanotubes. More importantly, this unique structure is well associated with graphene's large specific surface area, excellent mechanical property,[2] high room-temperature intrinsic electron mobility[3–5] and thermal conductivity,[6] making graphene a “star” material that has attracted enormous attentions in a wide range of areas including energy conversion and storage materials,[7–11] electronic devices,[12–14] sensors,[15–20] biological materials,[21] catalysis,[22] etc. With the one-decade ongoing research efforts devoted to this marvelous material, the focus of the chemical scientists has moved by and by from the pure chemical synthesis of graphene to the controlled construction of ordered graphene nano/macro structures and designated applications of graphene in different advanced systems. In particular, smart systems that can spontaneously respond to environmental changes, such as pH, temperature, electrical, light and other stimuli, are of great theoretical and practical interests, as they work to mimic living organisms and could be used for diverse applications ranging from actuators, robots to sensors. Owing to the above-mentioned excellent electrical, thermal and mechanical properties, graphene has been recognized as an effective additive or an active component by itself to boost the performance of these smart systems. In this review, we will discuss the recent development, contributed by us and other groups, in the stimulus-responsive graphene systems under various environmental stimuli, and present the potential trend in the future direction of this fast-growing research field. Since graphene can play either a passive role as a mere platform to provide conductivity/mechanical support or an active role as the stimulus-sensitive responsor by itself in the individual systems, the current review is thus structured to reflect this distinct difference in graphene's functionality.
2. Stimulus-Responsive Graphene Systems 2.1. Graphene as a Passive Platform/Supporting Substrate As graphene has excellent electrical, mechanical and thermal properties, it can function as an effective working platform to boost the important characteristics such as conductivity, robustness and sensitivity in different stimulus-responsive systems. Wang and coworkers prepared three-dimensional (3D) graphene assemblies from graphene oxide (GO) by a convenient in situ reduction with a combination of oxalic acid and sodium iodide.[23] The obtained 3D graphene network was shown to be an electrically conductive platform to infiltrate polydimethylsiloxane (PDMS) as an organicsolvent-sensing device to distinguish solvents with different polarity. In principle, PDMS exhibits a swelling process that is dependent on the polarity of various organic solvents, and the swelling of PDMS in turn blocks some of electrical
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conduction paths through the composite material, resulting in an increase in the overall resistance of the composite material. As shown in Figure 1a, when the composite was under a constant potential of 0.01 V, an environmental stimulus such as a droplet of a solvent on its surface led to the decrease of the current signal through the PDMS/graphene composite due to the fast swelling of the PDMS within several seconds. The current could return to its original value after the evaporation of the solvent, and the variation in the current was found to be in line with the relative polarity of the solvent (the relative polarity of ethanol, acetone, and chloroform are 0.654, 0.355, and 0.259, respectively), realizing a smart system responsive to environmental solvent polarity. Zhang et al. mixed 10,12-pentacosadiynoicacid as a diacetylene (DA) monomer and polymethylmethacrylate (PMMA) with graphene and then photopolymerized DA to form the PDA–PMMA/graphene composite as a one-shot electric current sensing material.[24] As illustrated in Figure 1b, the PDA–PMMA/graphene composite underwent an irreversible blue–red phase transition upon an externally applied current, where the addition of PMMA in the composite made the color transition more conspicuous, and the critical responsive current of this color change was found to be linearly dependant on the graphene content. The phenomenon was rationalized by the reduction of effective conjugation length induced by the conformation change of PDA backbone upon electrical stimulation. As the very thin PDA layer had strong interaction with the graphene via the hydrogen-bond interaction, the critical electrical stimulus required to initiate the conformation change of PDA was therefore directly related to the graphene content, rendering the possibility to use this material as an indicator in certain overcurrent protection circuits with different critical currents. Recently, we have devised several graphene systems that responded to the magnetic stimulus in the environment. Magnetic Fe3O4 nanoparticles were selected as the active working component to be embedded in graphene quantum dot assembled microspheres (GQDSs)[25] and one-dimensional (1D) graphene fibers (GFs),[26] enabling them to move or bend under the applied magnetic field as the response (Figure 1c,d). Additionally, a 3D graphene–Fe3O4 nanocomposite was synthesized by simple hydrothermal grafting reaction to exploit the low-density, high specific surface area of 3D graphene framework and the distinctive microwaveabsorbing ability of Fe3O4.[27] As graphene provided a large contact surface for individual dispersion of well-adhered Dr. J. Zhang,[+] L. Song,[+] Prof. Z. Zhang, Dr. N. Chen, Prof. L. Qu Key Laboratory of Cluster Science Ministry of Education of China Beijing Key Laboratory of Photoelectronic/ Electrophotonic Conversion Materials School of Chemistry Beijing Institute of Technology Beijing, 100081, P. R. China E-mail: [email protected]; [email protected] [+] J. Z. and L. S. contributed equally to the work DOI: 10.1002/smll.201303080
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Fe3O4 particles and acted as an excellent substrate for the absorption of microwave that involved both dielectric loss and magnetic loss, the electromagnetic wave absorption characteristics of graphene–Fe3O4 nanocomposite were much better than that of the pure graphene and Fe3O4. For a graphene–Fe3O4 composite film with a thickness of 3 mm, the deep reflection loss reached -23.0 dB at about 11.5 GHz with a broad wave absorbing area of a reflection loss higher than -10 dB (90% of signal attenuation) in the frequency range of 9.2–15.0 GHz, demonstrating its good microwave absorbing ability in both low- and high- frequency bands. With its reasonable biocompatibility, graphene can also work as an effective platform for sensing changes in the biological environment. For instance, GO was shown to bind and quencher a single-stranded DNA (ssDNA) through unique DNA/GO interactions.[28] On the basis of this phenomenon, Fan and coworkers designed a graphene nanoprobe for fast and sensitive multicolor fluorescent DNA analysis.[29] As shown in Figure 2a, the fluorescence of the ssDNA probe (P1) tagged by FAM (carboxyfluorescein) was almost quantitatively quenched by GO, while it rested largely unchanged even in the presence of GO if P1 formed a duplex with its complementary target T1, suggesting the establishment of a sensing platform for quantitative DNA analysis. Theoretical simulations indicated ssDNA was strongly interacted with GO through the π-stacking interaction between the ring structures in its nucleobases and the conjugated units of the graphene, but in contrast, the double-stranded DNA (dsDNA) was not stably adsorbed on GO and retained its helical structure due to the shield of its nucleobases within the densely negatively charged phosphate backbone. Li et al. further demonstrated a more complex system that GO not only worked as fluorescence quencher but also as the transporter to deliver DNA into living cells.[30] As illustrated in Figure 2b, the nanomachine was
Zhipan Zhang received his doctorate degree from École Polytechnique Fédérale de Lausanne in 2008. After working at Dyesol Ltd, Monash University and the University of Calgary, he is now an Associate Professor at Beijing Institute of Technology. His research focuses on energy-related applications of new materials, particularly in photovoltaics and solar fuels.
Liangti Qu received a Ph.D. in Chemistry from Tsinghua University (Beijing, China) in 2004. He is now a Professor of Chemistry at the Beijing Institute of Technology and leads the nanocarbon research group. His research interests in materials chemistry mainly focus on the synthesis, functionalization and application of nanomaterials with carbon–carbon conjugated structures, including carbon nanotubes, graphene and conducting polymers.
based on the principal that triplex-forming oligonucleotide exhibited duplex–triplex transition at basic–acid conditions and the difference in the affinity of GO with ssDNA and triplex DNA would lead to sharp changes in the fluorescence signal of the nucleic acid. As GO was able to move across the cell membrane to fulfill intracellular delivery, this process could be used in probing pH changes during apoptosis in
Figure 1. (a) The real-time change of the current passing through the graphene–PDMS composite when solvents of ethanol, acetone, and chloroform were applied onto its surface. The applied potential was fixed at 0.01 V. Arrows indicated the application of organic solvents droplets on the surface composite (Reproduced with permission.[23] Copyright 2012 Royal Society of Chemistry). (b) Photographs under ambient light and images from fluorescent microscope for the PDA-PMMA/graphene composite before and after current stimulus (Reproduced with permission.[24] Copyright 2013, American Chemical Society). (c) The suspension of Fe3O4–GQDSs in petroleum ether and the magnetic separation of Fe3O4–GQDSs from petroleum ether under an external magnet (Reproduced with permission.[25] Copyright 2012, IOP Publishing Ltd). (d) The straight Fe3O4/graphene fiber and its response to the attraction of the magnet (Reproduced with permission.[26] Copyright 2012, Wiley-VCH). small 2014, 10, No. 11, 2151–2164
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Figure 2. (a) Scheme for the GO-based multicolor DNA analysis. Fluorescence spectra of mixture probes (P5, P6, P7) in the presence of different targets T5 (blue), T6 (red) and T7 (orange) with the excitation wavelengths of 494, 643, and 587 nm (Reproduced with permission.[29] Copyright 2010, Wiley-VCH). (b) Schematic illustration of the working principle of the duplex–triplex/GO nanocomplex. (Reproduced with permission.[30] Copyright 2013, Springer Verlag).
living Ramos cells where the initially quenched fluorescence of the nucleic acid significantly recovered with the decrease of pH induced by the acidification of vincristine sulfate.
2.2. Graphene/Polymer Composites for pH and Temperature Sensitive Systems As graphene can be chemically modified and facilely functionalized, it has been adopted into various stimuli-responsive
polymers for different applications. Fang et al. selected chitosan as a mediating agent to stabilize GO in the solution and then converted GO into reduced GO (rGO) through chemical reduction where rGO and chitosan could be noncovalently bonded through the amino and hydroxyl groups of chitosan via zwitterionic interaction and hydrogen bonding.[31] As shown in Figure 3a, the suspension of rGO/ chitosan was pH responsive and it changed from a homogenous solution to a cloudy one as the pH increased from below 6 to above 8, with its transmittance increased from
Figure 3. (a) Left, transmittance of the supernatants of rGO/chitosan suspensions with different pH values after sedimentations. Right, schematic illustration of the reversible changes of the rGO/chitosan in aqueous media with pH as a stimulus (Reproduced with permission.[31] Copyright 2010 American Chemical Society). (b) Photographs of chitosan-functionalized rGO aqueous solutions with different pH values from 2.0 to 12.0 (Reproduced with permission.[32] Copyright 2012, Elsevier B.V.).
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Figure 4. (a) Schematic illustration of the GO–block polymer composite and its application as a thermal sensor. (b) Reversibility test of the on–off switching behavior in terms of PL quenching (Reproduced with permission.[35] Copyright 2013 Royal Society of Chemistry). (c) Upper, synthesis of AucorePtshell nanoparticles on graphene sheets by a galvanic replacement strategy and later attachment of the dextran-based smart polymer with thiol-ends. Lower, the photos and sketch maps of the hybrid catalyst in water below/above LCST (Reproduced with permission.[38] Copyright 2013, Royal Society of Chemistry).
about 20–80% after sedimentation in the meantime. This was rationalized by a chitosan-conformation induced rGO aggregation process. Chitosan was known to be pH-responsive with highly extended molecular chains at low pH, while at higher pH values, its deprotonation to form intermolecular associates through hydrogen bonding induced the aggregation of rGO (Figure 3a right), validating a reversible pHresponsive graphene system. Liu et al. further developed this system and obtained stable dispersion of chitosan-functionalized rGO at pH values of over 9, where the ionization of graphene mainly dominated the surface charge of the composite and led to a stable dispersion (Figure 3b).[32] They found that the increase of the chitosan coverage and cross-linking in the system resulted in dispersion only in acidic solution but not in neutral and basic solutions as shown in ref. [[31]], due to the strong electrostatic shielding effect of cross-linked chitosan on rGO. Differently, Lee and coworkers grafted poly(acrylic acid) (PAA) brushes on functionalized GO via surface-initiated atom transfer radical polymerization (SI-ATRP) and a subsequent hydrolysis reaction to obtain aqueous dispersion of graphene nanocomposites with pH-tunability.[33] The GO– PAA composite tended to aggregate at pH = 1 but remained dispersed at pH = 5 and 9, owing to the reversible conformational changes of PAA macromolecules between the collapsed and extended states at different pH values. Ren et al. also reported a pH responsive graphene–polyacrylamide (G– PAM) system that precipitated at low pH of 2.9 but dispersed homogeneously in water at pH higher than 4.[34] Interestingly, PAM molecules were known to have no pH responsive property, and therefore, this pH response was attributed to the possible hydrolyzation of PAM side chains (–CONH2) into acrylate during the reduction of GO to form G–PAM. When a thermally sensitive polymer such as poly(N-isopropylacrylamide) (PNIPAM) was incorporated, graphene small 2014, 10, No. 11, 2151–2164
systems could be temperature-responsive. Yang et al. constructed a GO-based temperature sensing platform by functionalizing GO with P7AC-b-PNIPAM-b-PSN3 triblock copolymers that were composed of poly(7-(4-(acryloyloxy) butoxy)coumarin) (P7AC) as the fluorescent component, PNIPAM as the thermally responsive polymer, and a short poly(azidostyrene) (PSN3) block as covalently binding unit to the GO surface (Figure 4a).[35] When the temperature of the solution was higher than 32 °C, the lower critical solution temperature (LCST) of PNIPAM, the photoluminescence (PL) of GO–block polymer composite decreased dramatically while the PL of pristine block polymer remained unchanged. This was understood by the changes of the conformation of PNIPAM with the temperature. As PNIPAM became hydrophobic with the condensed chain conformation in water above its LCST, the inter-space between the P7AC and the GO surface decreased, thus facilitating an efficient Förster resonance energy transfer (FRET) between the blue-emitting coumarins in the P7AC block and GO that quenched the PL. As is shown in Figure 4b, the quenched fluorescence could be fully recovered upon cooling the solution to a temperature below LCST and the system could be continuously cycled between the PL on–off states, owing to the reversible conformation changes of PNIPAM chains between the condensed and extended states with the temperature variation. In a different approach, Fan et al. prepared grafted PNIPAM onto GO by in situ free-radical polymerization and found that the conformation change of PNIPAM with the temperature led to unique crumpling feature of GO–PNIPAM hybrids when dried above LCST.[36] They further demonstrated that modifying graphene with PNIPAM-grafted dextran (DexPNI) could also induce graphene’s sensitivity to external temperature variations. When the temperature of a clear DexPNI–GO dispersion was
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increased from 25 °C to 40 °C, DexPNI–GO content totally precipitated and the solution became nearly transparent. When the heated suspension was cooled back to 25 °C, the dispersity of DexPNI–GO could be facilely recovered by gentle shaking, showing reversible temperature-induced aggregation/dispersion behaviors of DexPNI–NGO.[37] Interesting, the same group designed a smart catalytic system with temperature responsive catalytic behaviors by covalently linking a dextran-based PNIPAM polymer with thiol-ends to AucorePtshell bimetallic nanoparticles supported by the graphene (G–Au@Pt) (Figure 4c).[38] When the system was used in the catalytic reduction of 4-nitrophenol by NaBH4, the apparent pseudo-first-order rate constant, kapp, was found to increase linearly in the temperature range of 15–30 °C, in line with the well-known Arrhenius law, but decreased significantly when the temperature reached 35 °C (higher than the LCST of PNIPAM). The PNIPAM chains underwent the hydrophilic to hydrophobic phase transition between 30 and 35 °C and induced a macroscopic agglomeration and precipitation of the catalyst (photos in Figure 4c), therefore resulting in a complete shielding of the catalytically active sites of Au@ Pt nanoparticles and the decreased kapp. It should be further noted that it is possible to have graphene–polymer systems responsive simultaneously to pH and temperature if a pH sensitive block such as acrylic acid (AA) is introduced into the polymer backbone. Sun et al. synthesized GO interpenetrating PNIPAM-AA hydrogel networks by connecting GO sheets and PNIPAM-co-AA microgels with covalent bonds, where the GO/PNIPAM-AA showed a reversible shape change upon heating/cooling between 20 and 50 °C and a pH dependence of volume phase transition temperature (VPTT).[39] Similarly, Ye and coworkers built a pH- and temperature-responsive PNIPAM/AA/GO double network (DN) hydrogel via a two-step sequential free-radical polymerization.[40] The introduction of GO in the DN hydrogel
was found to effectively decrease the VPTT of the PNIPAM/ PAA hydrogel from approximately 32 °C to around 29 °C and increase the response rate of the DN hydrogel, which were rationally attributed to the high thermal conductivity of graphene. As a result, GO containing DN hydrogels had a fast response to pH/temperature variation and swelled as the temperature changed from 35 °C to 20 °C or the pH varied from 4 to approximately 8, proving the concept of graphene systems responsive dually to pH and temperature stimuli. The establishment of smart graphene systems that spontaneously respond to environmental stimuli renders the possibility to construct intracellular carrier for drug deliveries, such as anticancer drugs doxorubicin (DOX) and camptothecin (CPT). Li and coworkers prepared a graphene hybrid by the simultaneous reduction of GO and assembly of Pluronic F127 (PF127) and rGO.[41] The amphiphilic nature of PF127 helped the dispersion of rGO in physiological environment, with the hydrophobic segments of PF127 anchoring at the surface of graphene via hydrophobic interaction while the hydrophilic chains of PF127 extending to the solution. Impressively, the loading efficiency of the PF127/rGO hybrid for DOX could reach 289% (w/w) due to the strong interaction of π–π stacking, and the release of DOX was faster in acidic media than in neutral and basic media as a trade-off between the change of hydrogen bonding and different solubility of DOX at different pH values. The same group further designed an engineered redox-responsive graphene system, NGO–SS–mPEG, composed of nano-GO (NGO) sheets with a sheddable methoxy-polyethylene-glycol (mPEG) shell attached via a disulfide linkage (Figure 5a).[42] Similar to PF127, the mPEG moiety stabilized NGO in the physiological environment, thus facilitating the loading and releasing of the drug doxorubicin hydrochloride (DXR). Meanwhile, the disulfide linkage was inclined to undergo rapid cleavage through exchange reaction of thiol ligands induced by the
Figure 5. Schematic diagram showing antitumor activity of redox-sensitive DXR-loaded NGO-SS-mPEG. (a) PEG-shielded NGO with disulfide linkage for prolonged blood circulation. (b) Endocytosis of NGO-SS-mPEG in tumor cells via the EPR effect. (c) GSH trigger (GSH > fourfold relative to normal cells) resulting in PEG detachment. (d) Rapid drug release on the tumor site (Reproduced with permission.[44] Copyright 2011, Wiley-VCH).
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difference between extracellular and intracellular glutathione (GSH) concentrations in some tumor cells. Cell proliferation assays with HeLa cells clearly demonstrated the pharmacological efficacy of DXR released from NGO–SS– mPEG in the presence of enhanced GSH concentrations, verifying the GSH-triggered intracellular release of DXR for antitumor activities. In a similar work, AlNahain et al. used a thiol grafted Pluronic (PLU–SH) to form disulfide bonds surrounded rGO/PEG matrix, achieving up to around 35% higher DOX loading efficiency together with the controlled release of DOX triggered by GSH and pH.[43] Besides redox and pH stimuli, thermal stimulus could potentially initiate the drug delivery in graphene systems containing thermo-responsive PNIPAM as well. Pan et al. grafted PNIPAM onto GO sheets via click chemistry and used PNIPAM–GO as the carrier for CPT through hydrophobic interactions and π–π stacking.[44] The Figure 6. (a) Optical microscope images of GO/TiO2 nanocomposite (15 wt% particle PNIPAM–GO loaded CPT up to 15.6 wt% concentration) based ER fluid without an electric field (left) and with an electric field (right) and demonstrated a stable and continuous (Reproduced with permission.[45] Copyright 2011 Royal Society of Chemistry). (b) Photographs drug release during the in vitro test, with of the GO sheet-based ER fluid prepared by centrifugation of dispersion of GO sheets in (c) Extrusion of the GO sheet-based a potency of a 20% growth inhibition at ethanol (upper phase) and silicone oil (lower phase). [47 ER fluid from a needle (Reproduced with permission. ] Copyright 2012, Royal Society of −6 M. Unfortua concentration of 1 × 10 Chemistry). nately, no temperature-dependant drug releasing kinetics were studied in the work, demanding addi- and coworkers employed a solvent-exchange approach to tional efforts to explore the possibility to thermally control prepare easily-processed, GO-based ER fluids with isolated GO sheets (Figure 6b,c).[47] Due to the minimization of π-π the release of CPT from the graphene matrix. interaction between GO sheets and the electrostatic repulsion between oxygen functional groups, solvent-exchanged 2.3. Electro-Responsive Graphene Systems GO sheets had a settling velocity about 1600 times slower than that of conventional mechanically ground GO sheets, 2.3.1. Electrorheology thus forming no sediment after ninety days. Compared Electrorheological (ER) materials are usually suspensions to the ER efficiency of 67% at a shear rate of 100 s−1 for of polarizable dielectric or semiconducting tiny particles in mechanically ground GO, the solvent exchanged GO insulating oils. They are capable of reversibly changing from sheets demonstrated a tripled ER efficiency of 207%, posa Newtonian fluid state to a fibrillar solid-like state under sibly because its higher surface area provided sufficient the application of an external electric field. Choi and cow- electrostatic interaction to counteract the hydrodynamic orkers decorated GO with TiO2 nanoparticles by a nega- inter-action under shear flow. They further decorated GO tive–positive electrostatic attraction method and studied sheets with TiO2 nanorods and reported an ER efficiency the ER property of the hybrid material.[45] As shown in of 554% at a shear rate of 100 s−1.[48] Meanwhile, the GO/ Figure 6a, when the ER fluid was placed between two par- TiO2 nanorods composite even showed electro-responsive allel electrodes separated at 300 μm under an electric field, performance in an extremely low concentration of
