news & views arising from electrons or other ions. An activation energy of 0.2 eV was derived from temperature-dependent measurements and Arrhenius plots, and compares well with the energy required for a proton to hop from one water molecule to the next as part of the Grotthuss process (Fig. 1c). The conductivity of other reflectin-like proteins — produced by mutagenesis — was also tested. First, residues containing a carboxylic acid (aspartic acid and glutamic acid) were replaced with alanine. This substitution resulted in a reflectin derivative with lower proton conductivity. Gorodetsky and colleagues suggest that the protons available for conductivity in the wild-type form of reflectin originate from deprotonation of the carboxylic groups. Removing the amino acids that contain carboxylic acid groups thus shuts down the protonic conductivity. This phenomenon is similar to what happens with sulfonic acid groups in the well-known proton-conducting polymer, Nafion. More interestingly, scrambling the protein sequence without changing any amino acids also results in a reflectin derivative with lower proton conduction compared with the wild type. It is suggested that the wild-type reflectin sequence is conducive to better protein organization with a larger number of ordered proton wires. Unfortunately, the exact quaternary structures of the wild-type protein or the scrambled protein are not yet available. Regardless, this observation certainly raises an interesting question for further studies concerning the relationship between reflectin quaternary structure and its protonic conductivity. In the future, further mutagenesis and conductivity studies would be useful to help establish design rules and optimize conductivity in these types of protein-based material. Another
question along these lines is whether there is something special about reflectin. Reports of proton conductivity in collagen5, for example, can be found in the literature and almost all biomacromolecules absorb water when hydrated and are likely to form proton wires. Gorodetsky and co-workers go on to make protein-based proton-conducting field-effect transistors (H+-FETs). PdHx source and drain contacts are used to ensure proton exchange between the contacts and the reflectin channel according to the following equilibrium: PdH Pd + H+ + e–. These H+-FETs show a relatively small on–off ratio, which has plenty of room for improvement through the optimization of the device geometry and perhaps a protein derivative with a lower number of charge carriers. A remarkable mobility of ~7 × 10–3 cm–2 V–1 s–1 was recorded. This mobility is very similar to the mobility of protons in dilute acid solutions and compares favourably with the electronic mobility of polymer-based electronic conductors, especially when taking into consideration that protons are a couple of thousand times heavier than electrons. These are, however, not the first H+-FETs — ones with chitin-based polysaccharides6,7 and Nafion8 have been reported. Coincidentally, chitin is also found in squid — specifically in the gladius or pen (an evolutionary leftover of a mollusc shell) instead of the skin. Nevertheless, the reflectin-based H+-FETs reported here by Gorodetsky and co-workers hold a lot of promise. Using reflectin in H+-FETs offers the possibility of exploring a vast range of protein structures available through mutagenesis. By borrowing some of the amino acid motifs optimized by nature for conductivity, selectivity for protons versus other ions, and active transport, a range of
different devices based on proton-channel mimics with these proteins can be envisaged. Whether these proton-conducting reflectins will find applications in energy or bioelectronics remains to be seen. There are certainly attractive opportunities for these protein-based proton conductors, but also several challenges. For energy applications, reflectins need a boost in conductivity to be truly competitive with Nafion, and proven long-term durability to survive the high temperatures and acidity levels in fuel cells. The necessary performance boost may be achieved with protein derivatives exhibiting a higher proton mobility (as a consequence of a more ordered structure) or a higher charge-carrier density (arising from a higher proportion of acidic residues). For bioelectronics in physiological conditions, protein FETs will require smart design tricks to circumvent charge screening of the gate potential from other ions. Perhaps the most exciting future for this work is in investigating whether reflectin proton conductivity plays a role in the squid’s ability to change the colouration of its skin, and use this knowledge to develop devices that couple optical properties with proton transport. ❐ Marco Rolandi is in the Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195-2120, USA. e-mail: [email protected] References 1. Ordinario, D. D. et al. Nature Chem. 6, 596–602 (2014). 2. Crookes, W. J. et al. Science 303, 235–238 (2004). 3. Nagle, J. F. & Morowitz, H. J. Proc. Natl Acad. Sci. USA 75, 298–302 (1978). 4. DeCoursey, T. E. & Hosler, J. J. Roy. Soc. Interface 11, 20130799 (2014). 5. Bardelmeyer, G. H. Biopolymers 12, 2289–2302 (1973). 6. Zhong, C. et al. Nature Commun. 2, 476 (2011). 7. Deng, Y. et al. Sci. Rep. 3, 2481 (2013). 8. Deml, A. M., Bunge, A. L., Reznikov, M. A., Kolessov, A. & O’Hayre, R. P. J. Appl. Phys. 111, 074511 (2012).
COVALENT ORGANIC FRAMEWORKS
Crossing the channel
The ordered one-dimensional nanochannels found in covalent organic frameworks (COFs) could render them able to conduct protons. However, the frameworks’ instability in acid has thus far precluded any practical implementations. Now, a strategy to overcome this instability has enabled proton conduction using a COF for the first time.
Hong Xu and Donglin Jiang
T
he search for a high-performance proton-conducting material for use in fuel cells is central to the development of efficient methods to convert energy from chemicals — such as hydrogen, methanol or small hydrocarbons — into electricity. 564
At the anode of a hydrogen-fuelled cell, hydrogen is catalytically split into electrons and protons. The electrons are transferred to a cathode through an external circuit and produce direct current. The protons, however, are transported across a proton-
conducting membrane to the cathode, where they react with oxygen to produce water as a by-product. This proton-conducting membrane is key to the operation of the fuel cell. As well as efficiently transporting protons, this membrane needs to be stable
NATURE CHEMISTRY | VOL 6 | JULY 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
news & views at high temperatures and under both acidic and basic conditions to make it viable for long-term use. The first commercially available and the most well-established proton-conducting material is a perfluorinated sulfonated polymer, Nafion, which was discovered by DuPont in the 1960s. The unique morphological structure of Nafion facilitates proton transport through its oriented ionic nanochannels, and it is currently regarded as the benchmark for proton-conducting materials1. However, Nafion membranes are not without their problems; their high cost and low working temperatures make them unsuitable for medium-temperature fuel cell applications (120–200 °C). Crystalline porous materials with builtin and ordered channels are promising candidates for supplanting Nafion. Metal– organic frameworks (MOFs) can facilitate
proton conduction by accommodating guest molecules, such as water and imidazole, in well-defined pores or integrating functional acidic groups onto the channel walls2. However, because deprotonation of the occluded guests can cause rupture of coordination bonds and therefore the entire framework, their low tolerance for changes in pH remains a major drawback. Moreover, their high gravimetric weight, instability at high temperatures and the difficulty in forming compact membranes from them are issues yet to be addressed in the development of proton-conducting MOF materials. As they report 3 in the Journal of the American Chemical Society, Rahul Banerjee and co-workers have now taken a step towards using COFs as proton-conducting materials. Similar to MOFs but utilizing covalent rather than metal–ligand bonding, COFs4–6 are a class of crystalline porous
a
polymers that enable atomically precise integration of organic units into periodic structures, including one-dimensional channels similar to those found in Nafion. COFs are relatively lightweight and possess high thermal stability, both of which are important factors for their practical application in fuel cells. However, the chemical instability of COFs under acidic conditions has posed a challenge in this respect. COFs built from a framework of reversible boronate-ester, imine, hydrazone and azine linkages3 are all unstable because acid triggers the reverse reaction and destroys the frameworks. Banerjee and co-workers have synthesized an azo (–N=N–)-functionalized COF (Tp-Azo COF) using the reversible Schiff base reaction between 1,3,5-triformylphloroglucinol (Tp) and 4,4ʹ-azodianiline (Azo). The COF formation
N
CHO
HO OHC
OH
HO
OH
N N
CHO
N HO
1,3,5-triformylphloroglucinol (Tp)
N
4,4ʹ-azodianiline (Azo)
OH N
N
N
N
N
OH
N
N
N N N
HO N
N N
N N HO
O
OH
NH
OH N
b
N N
NH O
N N NH O
O HN
N
Tp-Azo COF
O H N
N N
N
O HN
N
NH O
O HN
N
OH
HO
N
N
N
OH OH N
Enol–keto tautomerization
O
N H O
O HN
OH
HO
N HO
NH O
N HO
N
N
NH2
O H N
N
HO
NH2
N
NH OH
N NH O O
N
NH O O NH
N
N H O
NH
c
Figure 1 | The structure and proton-conducting mechanism of Tp-Azo COF. a, Schiff base reaction followed by irreversible enol-to-keto tautomerization locks the COF structure. b, View down Tp-Azo COF showing the hexagonal one-dimensional channels through which proton conduction can occur. The enlarged inset shows an analogous crystal structure that illustrates the hydrogen-bonding interaction between a protonated azo unit in Tp-Azo COF and phosphonate ion. These further interact with free phosphoric acid to form hydrogen-bonding networks8 within the channels of Tp-Azo COF (red, O; blue, N; white, H; grey, C; orange, P; broken light-blue lines, hydrogen bonds). c, Graphical representation of proton conduction along the 1D channels (green sphere, proton). NATURE CHEMISTRY | VOL 6 | JULY 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
565
news & views reaction includes two steps: first, the Schiff base reaction leads to the formation of a crystalline porous framework, and the second step is an irreversible enol-to-keto tautomerization, which blocks the reverse reaction7 (Fig. 1a). Unlike other COFs, this renders Tp-Azo COF especially robust towards changes in pH, and it retains both its crystallinity and porosity in boiling water and strong acid (9 N HCl) for seven days. Interestingly, it exhibits only moderate stability under basic conditions (3–6 N NaOH), with only partial retention of crystallinity and porosity. Pristine Tp-Azo COF has high porosity with a Brunauer–Emmett–Teller surface area of 1,328 m2 g–1 and mesopores of 3.1 nm. Such high porosity is an advantage as it allows accommodation of more guest molecules to serve as proton transport media. Stability towards acidic conditions is the first precondition for using such materials for proton conduction; however as Tp-Azo COF exhibits almost zero conductivity alone, the second precondition is the loading of a proton-conductive compound. To this end, a simple impregnation process loaded phosphoric acid inside the framework up to 5.4 wt%. The azo units of Tp-Azo COF were protonated and formed hydrogen-bonding interactions with the H2PO4– anion8, which further interacted with free phosphoric acid molecules to form a hydrogen-bonding network in the onedimensional channels (Fig. 1b). As a result
of this impregnation, Tp-Azo COF exhibited proton conductivities of 6.7 × 10–5 S cm–1 under anhydrous conditions and 9.9 × 10–4 S cm–1 under 98% relative humidity, respectively. The different conductivities originate from different ionization modes; under anhydrous conditions, proton conduction is driven purely by selfdissociation of phosphoric acid. In contrast, under humid conditions phosphoric acid is deprotonated to form H3O+ and this facilitates transport much more effectively. These proton conductivities are a little lower than, but broadly comparable to, those of highly proton-conducting MOFs2. Tp-Azo COF exhibited an activation energy for proton conduction of only 0.11 eV, which is lower than that of Nafion (0.22 eV) and MOFs operating under humid conditions (0.14–0.6 eV)2. The low activation energy suggests that the proton probably hops along the hydrogen-bonding networks in the nanochannels (Fig. 1c). As phosphoric acid is a particularly good proton transport medium and is suitable for medium-temperature fuel cells, the fact that this COF system enables its use means it has potential for medium-temperature fuel-cell applications. In comparison, MOFs rarely retain their crystalline structures under strong acidic conditions and have not been reported to perform proton conduction in the presence of phosphoric acid. The highly ordered one-dimensional channels in COFs offer potential pathways
for proton conduction. The work that has been carried out by Rahul Banerjee and colleagues has, for the first time, demonstrated the possibility of using COFs for proton conduction. This development opens up exciting opportunities for the development of proton-conducting materials — but improving their conductivity and establishing whether COFs can be formed into suitable membranes are important aspects that require further investigation before they will find practical application. On the other hand, it is possible to design and control the functionalization of both frameworks and pores in COFs, and so they offer an appealing platform for construction of proton-conducting systems for applications in fuel cells, sensors and electronic devices. ❐ Hong Xu and Donglin Jiang are in the Department of Materials Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan. e-mail: [email protected] References 1. Schmidt-Rohr, K. & Chen, Q. Nature Mater. 7, 75–83 (2008). 2. Yoon, M., Suh, K., Natarajan, S. & Kim, K. Angew. Chem. Int. Ed. 52, 2688–2700 (2013). 3. Chandra, S. et al. J. Am. Chem. Soc. 136, 6570–6573 (2014). 4. Feng, X., Ding, X. & Jiang, D. Chem. Soc. Rev. 41, 6010–6022 (2012). 5. Jin, S. et al. Angew. Chem. Int. Ed. 52, 2017–2021 (2013). 6. Xu, H. et al. Chem. Commun. 50, 1292–1294 (2014). 7. Kandambeth, S. et al. J. Am. Chem. Soc. 134, 19524–19527 (2012). 8. Halasz, I., Lukic, K. & Vancik, H. Acta Crystallogr. C 63, o61–o64 (2007).
VIRUS ENGINEERING
Fighting HIV at its own game
Live-attenuated viruses used in vaccines can regain their virulence, which for deadly viruses such as HIV is an unacceptable risk. Now, attenuated HIV-1 viruses, which include mutations that genetically encode unnatural amino acids and prevent them from replicating in normal cells, have been constructed.
Shixian Lin and Peng R. Chen
P
reventing the global spread of human immunodeficiency virus-1 (HIV-1) has been a great challenge for scientists. Even with increasing access to life-saving antiretroviral therapies, the number of people living with HIV-1 continues to grow. An effective HIV-1 vaccine remains elusive and was once regarded as impossible due to the apparent difficulty of getting the immune system to produce a broadly neutralizing antibody response. Results from recent studies1,2 and a vaccine trial3 brought new hope to the HIV-1 vaccine field. The use of live-attenuated simian 566
immunodeficiency virus vaccines has been very successful in protecting nonhuman primates against homologous simian immunodeficiency virus infection1. However, it is often observed that these attenuated vaccines can revert over time to virulent forms that cause disease in vaccinated animals due to persistent replication and subsequent mutations that restore virulence. Deletions or modifications in accessory genes of attenuated viruses can improve vaccine safety, but at the expense of vaccine efficacy; therefore alternative biochemical strategies are required to
construct safer vaccines that cannot replicate in patients. The genetic encoding of unnatural amino acids has been used in a diverse range of biochemical and biomedical applications and can be conducted in a variety of living species4,5. Typically this involves reprogramming a blank DNA codon (a codon that does not encode a natural amino acid, such as the amber nonsense codon) by including additional cellular replication machinery that enables the blank codon to encode for an unnatural amino acid. However, extending this highly
NATURE CHEMISTRY | VOL 6 | JULY 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
question along these lines is whether there is something special about reflectin. Reports of proton conductivity in collagen5, for example, can be found in the literature and almost all biomacromolecules absorb water when hydrated and are likely to form proton wires. Gorodetsky and co-workers go on to make protein-based proton-conducting field-effect transistors (H+-FETs). PdHx source and drain contacts are used to ensure proton exchange between the contacts and the reflectin channel according to the following equilibrium: PdH Pd + H+ + e–. These H+-FETs show a relatively small on–off ratio, which has plenty of room for improvement through the optimization of the device geometry and perhaps a protein derivative with a lower number of charge carriers. A remarkable mobility of ~7 × 10–3 cm–2 V–1 s–1 was recorded. This mobility is very similar to the mobility of protons in dilute acid solutions and compares favourably with the electronic mobility of polymer-based electronic conductors, especially when taking into consideration that protons are a couple of thousand times heavier than electrons. These are, however, not the first H+-FETs — ones with chitin-based polysaccharides6,7 and Nafion8 have been reported. Coincidentally, chitin is also found in squid — specifically in the gladius or pen (an evolutionary leftover of a mollusc shell) instead of the skin. Nevertheless, the reflectin-based H+-FETs reported here by Gorodetsky and co-workers hold a lot of promise. Using reflectin in H+-FETs offers the possibility of exploring a vast range of protein structures available through mutagenesis. By borrowing some of the amino acid motifs optimized by nature for conductivity, selectivity for protons versus other ions, and active transport, a range of
different devices based on proton-channel mimics with these proteins can be envisaged. Whether these proton-conducting reflectins will find applications in energy or bioelectronics remains to be seen. There are certainly attractive opportunities for these protein-based proton conductors, but also several challenges. For energy applications, reflectins need a boost in conductivity to be truly competitive with Nafion, and proven long-term durability to survive the high temperatures and acidity levels in fuel cells. The necessary performance boost may be achieved with protein derivatives exhibiting a higher proton mobility (as a consequence of a more ordered structure) or a higher charge-carrier density (arising from a higher proportion of acidic residues). For bioelectronics in physiological conditions, protein FETs will require smart design tricks to circumvent charge screening of the gate potential from other ions. Perhaps the most exciting future for this work is in investigating whether reflectin proton conductivity plays a role in the squid’s ability to change the colouration of its skin, and use this knowledge to develop devices that couple optical properties with proton transport. ❐ Marco Rolandi is in the Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195-2120, USA. e-mail: [email protected] References 1. Ordinario, D. D. et al. Nature Chem. 6, 596–602 (2014). 2. Crookes, W. J. et al. Science 303, 235–238 (2004). 3. Nagle, J. F. & Morowitz, H. J. Proc. Natl Acad. Sci. USA 75, 298–302 (1978). 4. DeCoursey, T. E. & Hosler, J. J. Roy. Soc. Interface 11, 20130799 (2014). 5. Bardelmeyer, G. H. Biopolymers 12, 2289–2302 (1973). 6. Zhong, C. et al. Nature Commun. 2, 476 (2011). 7. Deng, Y. et al. Sci. Rep. 3, 2481 (2013). 8. Deml, A. M., Bunge, A. L., Reznikov, M. A., Kolessov, A. & O’Hayre, R. P. J. Appl. Phys. 111, 074511 (2012).
COVALENT ORGANIC FRAMEWORKS
Crossing the channel
The ordered one-dimensional nanochannels found in covalent organic frameworks (COFs) could render them able to conduct protons. However, the frameworks’ instability in acid has thus far precluded any practical implementations. Now, a strategy to overcome this instability has enabled proton conduction using a COF for the first time.
Hong Xu and Donglin Jiang
T
he search for a high-performance proton-conducting material for use in fuel cells is central to the development of efficient methods to convert energy from chemicals — such as hydrogen, methanol or small hydrocarbons — into electricity. 564
At the anode of a hydrogen-fuelled cell, hydrogen is catalytically split into electrons and protons. The electrons are transferred to a cathode through an external circuit and produce direct current. The protons, however, are transported across a proton-
conducting membrane to the cathode, where they react with oxygen to produce water as a by-product. This proton-conducting membrane is key to the operation of the fuel cell. As well as efficiently transporting protons, this membrane needs to be stable
NATURE CHEMISTRY | VOL 6 | JULY 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
news & views at high temperatures and under both acidic and basic conditions to make it viable for long-term use. The first commercially available and the most well-established proton-conducting material is a perfluorinated sulfonated polymer, Nafion, which was discovered by DuPont in the 1960s. The unique morphological structure of Nafion facilitates proton transport through its oriented ionic nanochannels, and it is currently regarded as the benchmark for proton-conducting materials1. However, Nafion membranes are not without their problems; their high cost and low working temperatures make them unsuitable for medium-temperature fuel cell applications (120–200 °C). Crystalline porous materials with builtin and ordered channels are promising candidates for supplanting Nafion. Metal– organic frameworks (MOFs) can facilitate
proton conduction by accommodating guest molecules, such as water and imidazole, in well-defined pores or integrating functional acidic groups onto the channel walls2. However, because deprotonation of the occluded guests can cause rupture of coordination bonds and therefore the entire framework, their low tolerance for changes in pH remains a major drawback. Moreover, their high gravimetric weight, instability at high temperatures and the difficulty in forming compact membranes from them are issues yet to be addressed in the development of proton-conducting MOF materials. As they report 3 in the Journal of the American Chemical Society, Rahul Banerjee and co-workers have now taken a step towards using COFs as proton-conducting materials. Similar to MOFs but utilizing covalent rather than metal–ligand bonding, COFs4–6 are a class of crystalline porous
a
polymers that enable atomically precise integration of organic units into periodic structures, including one-dimensional channels similar to those found in Nafion. COFs are relatively lightweight and possess high thermal stability, both of which are important factors for their practical application in fuel cells. However, the chemical instability of COFs under acidic conditions has posed a challenge in this respect. COFs built from a framework of reversible boronate-ester, imine, hydrazone and azine linkages3 are all unstable because acid triggers the reverse reaction and destroys the frameworks. Banerjee and co-workers have synthesized an azo (–N=N–)-functionalized COF (Tp-Azo COF) using the reversible Schiff base reaction between 1,3,5-triformylphloroglucinol (Tp) and 4,4ʹ-azodianiline (Azo). The COF formation
N
CHO
HO OHC
OH
HO
OH
N N
CHO
N HO
1,3,5-triformylphloroglucinol (Tp)
N
4,4ʹ-azodianiline (Azo)
OH N
N
N
N
N
OH
N
N
N N N
HO N
N N
N N HO
O
OH
NH
OH N
b
N N
NH O
N N NH O
O HN
N
Tp-Azo COF
O H N
N N
N
O HN
N
NH O
O HN
N
OH
HO
N
N
N
OH OH N
Enol–keto tautomerization
O
N H O
O HN
OH
HO
N HO
NH O
N HO
N
N
NH2
O H N
N
HO
NH2
N
NH OH
N NH O O
N
NH O O NH
N
N H O
NH
c
Figure 1 | The structure and proton-conducting mechanism of Tp-Azo COF. a, Schiff base reaction followed by irreversible enol-to-keto tautomerization locks the COF structure. b, View down Tp-Azo COF showing the hexagonal one-dimensional channels through which proton conduction can occur. The enlarged inset shows an analogous crystal structure that illustrates the hydrogen-bonding interaction between a protonated azo unit in Tp-Azo COF and phosphonate ion. These further interact with free phosphoric acid to form hydrogen-bonding networks8 within the channels of Tp-Azo COF (red, O; blue, N; white, H; grey, C; orange, P; broken light-blue lines, hydrogen bonds). c, Graphical representation of proton conduction along the 1D channels (green sphere, proton). NATURE CHEMISTRY | VOL 6 | JULY 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
565
news & views reaction includes two steps: first, the Schiff base reaction leads to the formation of a crystalline porous framework, and the second step is an irreversible enol-to-keto tautomerization, which blocks the reverse reaction7 (Fig. 1a). Unlike other COFs, this renders Tp-Azo COF especially robust towards changes in pH, and it retains both its crystallinity and porosity in boiling water and strong acid (9 N HCl) for seven days. Interestingly, it exhibits only moderate stability under basic conditions (3–6 N NaOH), with only partial retention of crystallinity and porosity. Pristine Tp-Azo COF has high porosity with a Brunauer–Emmett–Teller surface area of 1,328 m2 g–1 and mesopores of 3.1 nm. Such high porosity is an advantage as it allows accommodation of more guest molecules to serve as proton transport media. Stability towards acidic conditions is the first precondition for using such materials for proton conduction; however as Tp-Azo COF exhibits almost zero conductivity alone, the second precondition is the loading of a proton-conductive compound. To this end, a simple impregnation process loaded phosphoric acid inside the framework up to 5.4 wt%. The azo units of Tp-Azo COF were protonated and formed hydrogen-bonding interactions with the H2PO4– anion8, which further interacted with free phosphoric acid molecules to form a hydrogen-bonding network in the onedimensional channels (Fig. 1b). As a result
of this impregnation, Tp-Azo COF exhibited proton conductivities of 6.7 × 10–5 S cm–1 under anhydrous conditions and 9.9 × 10–4 S cm–1 under 98% relative humidity, respectively. The different conductivities originate from different ionization modes; under anhydrous conditions, proton conduction is driven purely by selfdissociation of phosphoric acid. In contrast, under humid conditions phosphoric acid is deprotonated to form H3O+ and this facilitates transport much more effectively. These proton conductivities are a little lower than, but broadly comparable to, those of highly proton-conducting MOFs2. Tp-Azo COF exhibited an activation energy for proton conduction of only 0.11 eV, which is lower than that of Nafion (0.22 eV) and MOFs operating under humid conditions (0.14–0.6 eV)2. The low activation energy suggests that the proton probably hops along the hydrogen-bonding networks in the nanochannels (Fig. 1c). As phosphoric acid is a particularly good proton transport medium and is suitable for medium-temperature fuel cells, the fact that this COF system enables its use means it has potential for medium-temperature fuel-cell applications. In comparison, MOFs rarely retain their crystalline structures under strong acidic conditions and have not been reported to perform proton conduction in the presence of phosphoric acid. The highly ordered one-dimensional channels in COFs offer potential pathways
for proton conduction. The work that has been carried out by Rahul Banerjee and colleagues has, for the first time, demonstrated the possibility of using COFs for proton conduction. This development opens up exciting opportunities for the development of proton-conducting materials — but improving their conductivity and establishing whether COFs can be formed into suitable membranes are important aspects that require further investigation before they will find practical application. On the other hand, it is possible to design and control the functionalization of both frameworks and pores in COFs, and so they offer an appealing platform for construction of proton-conducting systems for applications in fuel cells, sensors and electronic devices. ❐ Hong Xu and Donglin Jiang are in the Department of Materials Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan. e-mail: [email protected] References 1. Schmidt-Rohr, K. & Chen, Q. Nature Mater. 7, 75–83 (2008). 2. Yoon, M., Suh, K., Natarajan, S. & Kim, K. Angew. Chem. Int. Ed. 52, 2688–2700 (2013). 3. Chandra, S. et al. J. Am. Chem. Soc. 136, 6570–6573 (2014). 4. Feng, X., Ding, X. & Jiang, D. Chem. Soc. Rev. 41, 6010–6022 (2012). 5. Jin, S. et al. Angew. Chem. Int. Ed. 52, 2017–2021 (2013). 6. Xu, H. et al. Chem. Commun. 50, 1292–1294 (2014). 7. Kandambeth, S. et al. J. Am. Chem. Soc. 134, 19524–19527 (2012). 8. Halasz, I., Lukic, K. & Vancik, H. Acta Crystallogr. C 63, o61–o64 (2007).
VIRUS ENGINEERING
Fighting HIV at its own game
Live-attenuated viruses used in vaccines can regain their virulence, which for deadly viruses such as HIV is an unacceptable risk. Now, attenuated HIV-1 viruses, which include mutations that genetically encode unnatural amino acids and prevent them from replicating in normal cells, have been constructed.
Shixian Lin and Peng R. Chen
P
reventing the global spread of human immunodeficiency virus-1 (HIV-1) has been a great challenge for scientists. Even with increasing access to life-saving antiretroviral therapies, the number of people living with HIV-1 continues to grow. An effective HIV-1 vaccine remains elusive and was once regarded as impossible due to the apparent difficulty of getting the immune system to produce a broadly neutralizing antibody response. Results from recent studies1,2 and a vaccine trial3 brought new hope to the HIV-1 vaccine field. The use of live-attenuated simian 566
immunodeficiency virus vaccines has been very successful in protecting nonhuman primates against homologous simian immunodeficiency virus infection1. However, it is often observed that these attenuated vaccines can revert over time to virulent forms that cause disease in vaccinated animals due to persistent replication and subsequent mutations that restore virulence. Deletions or modifications in accessory genes of attenuated viruses can improve vaccine safety, but at the expense of vaccine efficacy; therefore alternative biochemical strategies are required to
construct safer vaccines that cannot replicate in patients. The genetic encoding of unnatural amino acids has been used in a diverse range of biochemical and biomedical applications and can be conducted in a variety of living species4,5. Typically this involves reprogramming a blank DNA codon (a codon that does not encode a natural amino acid, such as the amber nonsense codon) by including additional cellular replication machinery that enables the blank codon to encode for an unnatural amino acid. However, extending this highly
NATURE CHEMISTRY | VOL 6 | JULY 2014 | www.nature.com/naturechemistry
© 2014 Macmillan Publishers Limited. All rights reserved
