Here, we report a new on-surface synthetic strategy to precisely introduce five-membered units into conjugated polymers from specifically designed precursor molecules that give rise to low-bandgap fulvalene-bridged bisanthene polymers. The selective formation of non-benzenoid units is finely controlled by the annealing parameters, which govern the initiation of atomic rearrangements that efficiently transform previously formed diethynyl bridges into fulvalene moieties. The atomically precise structures and electronic properties have been unmistakably characterized by STM, nc-AFM, and STS and the results are supported by DFT theoretical calculations. Interestingly, the fulvalene-bridged bisanthene polymers exhibit experimental narrow frontier electronic gaps of 1.2 eV on Au(111) with fully conjugated units. This on-surface synthetic strategy can potentially be extended to other conjugated polymers to tune their optoelectronic properties by integrating five-membered rings at precise sites.

Departamento de Química Orgánica Universidad de Granada Unidad de Excelencia de Química UEQ C U Fuentenueva Granada 18071 Spain

Faculty of Nuclear Sciences and Physical Engineering Czech Technical University Prague Brehova 7 Prague 1 115 19 Czech Republic

Institute of Physics Czech Academy of Sciences Prague 162 00 Czech Republic

J Department of Physical Chemistry Faculty of Science Palacký University Olomouc 78371 Czech Republic

Regional Centre of Advanced Technologies and Materials Czech Advanced Technology and Research Institute Palacký University Olomouc Olomouc 783 71 Czech Republic

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Qiu Z. Hammer B. A. G. Müllen K. Conjugated Polymers - Problems and Promises. Prog. Polym. Sci. 2020;100:101179. doi: 10.1016/J.PROGPOLYMSCI.2019.101179. doi: 10.1016/j.progpolymsci.2019.101179. DOI

Roncali J. Molecular Engineering of the Band Gap of π-Conjugated Systems: Facing Technological Applications. Macromol. Rapid Commun. 2007;28(17):1761–1775. doi: 10.1002/marc.200700345. doi: 10.1002/marc.200700345. DOI

Olivier Y. Niedzialek D. Lemaur V. Pisula W. Müllen K. Koldemir U. Reynolds J. R. Lazzaroni R. Cornil J. Beljonne D. 25th Anniversary Article: High-Mobility Hole and Electron Transport Conjugated Polymers: How Structure Defines Function. Adv. Mater. 2014;26(14):2119–2136. doi: 10.1002/ADMA.201305809. doi: 10.1002/adma.201305809. PubMed DOI

Parkhurst R. R., Swager T. M., Siegel J. S. and Wu Y.-T., Polyarenes II, Springer International Publishing, 2014, vol. 350, 10.1007/978-3-319-07302-6 DOI

Zeng Z. Shi X. Chi C. López Navarrete J. T. Casado J. Wu J. Pro-Aromatic and Anti-Aromatic p-Conjugated Molecules: An Irresistible Wish to Be Diradicals. Chem. Soc. Rev. 2015;44(18):6578–6596. doi: 10.1039/c5cs00051c. doi: 10.1039/C5CS00051C. PubMed DOI

Frederickson C. K. Rose B. D. Haley M. M. Explorations of the Indenofluorenes and Expanded Quinoidal Analogues. Acc. Chem. Res. 2017;50(4):977–987. doi: 10.1021/acs.accounts.7b00004. doi: 10.1021/acs.accounts.7b00004. PubMed DOI

Liu J. Mishra S. Pignedoli C. A. Passerone D. Urgel J. I. Fabrizio A. Lohr T. G. Ma J. Komber H. Baumgarten M. Corminboeuf C. Berger R. Ruffieux P. Müllen K. Fasel R. Feng X. Open-Shell Nonbenzenoid Nanogra-phenes Containing Two Pairs of Pentagonal and Heptagonal Rings. J. Am. Chem. Soc. 2019;141(30):12011–12020. doi: 10.1021/jacs.9b04718. doi: 10.1021/jacs.9b04718. PubMed DOI

Di Giovannantonio M. Eimre K. Yakutovich A. V. Chen Q. Mishra S. Urgel J. I. Pignedoli C. A. Ruffieux P. Müllen K. Narita A. Fasel R. On-Surface Synthesis of Anti-aromatic and Open-Shell Indeno[2,1- b]Fluorene Polymers and Their Lateral Fusion into Porous Ribbons. J. Am. Chem. Soc. 2019;141(31):12346–12354. doi: 10.1021/JACS.9B05335. doi: 10.1021/jacs.9b05335. PubMed DOI

Mishra S. Beyer D. Berger R. Liu J. Grö O. Urgel J. I. Müllen K. Ruffieux P. Feng X. Fasel R. Topological Defect-Induced Magnetism in a Nanographene. J. Am. Chem. Soc. 2020;142(3):1147–1152. doi: 10.1021/jacs.9b09212. doi: 10.1021/jacs.9b09212. PubMed DOI

Fujii S. Marqués-González S. Shin J.-Y. Shinokubo H. Masuda T. Nishino T. Narendra P. A. Vázquez H. Kiguchi M. Highly-Conducting Molecular Circuits Based on Antiaromaticity. Nat. Commun. 2017;8(1):1–8. doi: 10.1038/ncomms15984. doi: 10.1038/s41467-016-0009-6. PubMed DOI PMC

Zhang G. P. Xie Z. Song Y. Wei M.-Z. Hu G.-C. Wang C.-K. Is There a Specific Correlation between Conductance and Molecular Aromaticity in Single-Molecule Junctions? Org. Electron. 2017;48:29–34. doi: 10.1016/J.ORGEL.2017.05.032. doi: 10.1016/j.orgel.2017.05.032. DOI

Gil-Guerrero S. Ramos-Berdullas N. Mandado M. Can Aromaticity Enhance the Electron Transport in Molecular Wires? Org. Electron. 2018;61:177–184. doi: 10.1016/J.ORGEL.2018.05.043. doi: 10.1016/j.orgel.2018.05.043. DOI

Chujo Y., Conjugated Polymer Synthesis: Methods and Reactions, John Wiley & Sons, 2011

Grill L. Hecht S. Covalent On-Surface Polymerization. Nat. Chem. 2020;12(2):115–130. doi: 10.1038/s41557-019-0392-9. doi: 10.1038/s41557-019-0392-9. PubMed DOI

Clair S. de Oteyza D. G. Controlling a Chemical Coupling Reaction on a Surface: Tools and Strategies for On-Surface Synthesis. Chem. Rev. 2019;119(7):4717–4776. doi: 10.1021/ACS.CHEMREV.8B00601. doi: 10.1021/acs.chemrev.8b00601. PubMed DOI PMC

Grill L. Dyer M. Lafferentz L. Persson M. Peters M. V. Hecht S. Nano-Architectures by Covalent Assembly of Molecular Building Blocks. Nat. Nanotechnol. 2007;2(11):687–691. doi: 10.1038/nnano.2007.346. doi: 10.1038/nnano.2007.346. PubMed DOI

Mishra S. Lohr T. G. Pignedoli C. A. Liu J. Berger R. Urgel J. I. Müllen K. Feng X. Ruffieux P. Fasel R. Tailoring Bond Topologies in Open-Shell Graphene Nanostructures. ACS Nano. 2018;12(12):11917–11927. doi: 10.1021/acsnano.8b07225. doi: 10.1021/acsnano.8b07225. PubMed DOI

de Oteyza D. G. Gorman P. Chen Y.-C. Wickenburg S. Riss A. Mowbray D. J. Etkin G. Pedramrazi Z. Tsai H.-Z. Rubio A. Crommie M. F. Fischer F. R. Direct Imaging of Covalent Bond Structure in Single-Molecule Chemical Reac-tions. Science. 2013;340(6139):1434–1437. doi: 10.1126/SCIENCE.1238187. doi: 10.1126/science.1238187. PubMed DOI

Riss A. Pérez Paz A. Wickenburg S. Tsai H.-Z. de Oteyza D. G. Bradley A. J. Ugeda M. M. Gorman P. Sae Jung H. Crommie M. F. Rubio A. Fischer F. R. Imaging Single-Molecule Reaction Intermediates Stabilized by Surface Dissipation and Entropy. Nat. Chem. 2016;8(7):678–683. doi: 10.1038/NCHEM.2506. doi: 10.1038/nchem.2506. PubMed DOI

Shiotari A. Nakae T. Iwata K. Mori S. Okujima T. Uno H. Sakaguchi H. Sugimoto Y. Strain-Induced Skeletal Rearrangement of a Polycyclic Aromatic Hydrocarbon on a Copper Surface. Nat. Commun. 2017;8(1):1–8. doi: 10.1038/ncomms16089. doi: 10.1038/s41467-016-0009-6. PubMed DOI PMC

Li J. Sanz S. Corso M. Choi D. J. Peña D. Frederiksen T. Pascual J. I. Single Spin Localization and Manipula-tion in Graphene Open-Shell Nanostructures. Nat. Commun. 2019;10(1):1–7. doi: 10.1038/s41467-018-08060-6. doi: 10.1038/s41467-018-07882-8. PubMed DOI PMC

Pavliček N. Gawel P. Kohn D. R. Majzik Z. Xiong Y. Meyer G. Anderson H. L. Gross L. Polyyne Formation via Skeletal Rearrangement Induced by Atomic Manipulation. Nat. Chem. 2018;10(8):853–858. doi: 10.1038/s41557-018-0067-y. doi: 10.1038/s41557-018-0067-y. PubMed DOI PMC

Schuler B. Fatayer S. Mohn F. Moll N. Pavliček N. Meyer G. Peña D. Gross L. Reversible Bergman Cyclization by Atomic Manipulation. Nat. Chem. 2016;8(3):220–224. doi: 10.1038/NCHEM.2438. doi: 10.1038/nchem.2438. PubMed DOI

Tobe Y. Non-Alternant Non-Benzenoid Aromatic Compounds: Past, Present, and Future. Chem. Rec. 2015;15(1):86–96. doi: 10.1002/TCR.201402077. doi: 10.1002/tcr.201402077. PubMed DOI

Riss A. Wickenburg S. Gorman P. Tan L. Z. Tsai H. Z. de Oteyza D. G. Chen Y.-C. Bradley A. J. Ugeda M. M. Etkin G. Louie S. G. Fischer F. R. Crommie M. F. Local Electronic and Chemical Structure of Oligo-Acetylene Deriva-tives Formed through Radical Cyclizations at a Surface. Nano Lett. 2014;14(5):2251–2255. doi: 10.1021/NL403791Q. doi: 10.1021/nl403791q. PubMed DOI PMC

Riss A. Pérez Paz A. Wickenburg S. Tsai H.-Z. de Oteyza D. G. Bradley A. J. Ugeda M. M. Gorman P. Sae Jung H. Crommie M. F. Rubio A. Fischer F. R. Imaging Single-Molecule Reaction Intermediates Stabilized by Surface Dissipation and Entropy. Nat. Chem. 2016;8(7):678–683. doi: 10.1038/NCHEM.2506. doi: 10.1038/nchem.2506. PubMed DOI

Ruffieux P. Wang S. Yang B. Sánchez-Sánchez C. Liu J. Dienel T. Talirz L. Shinde P. Pignedoli C. A. Passerone D. Dumslaff T. Feng X. Müllen K. Fasel R. On-Surface Synthesis of Graphene Nanoribbons with Zigzag Edge Topology. Nature. 2016;531(7595):489–492. doi: 10.1038/nature17151. doi: 10.1038/nature17151. PubMed DOI

Orchin M. Reggel L. Aromatic Cyclodehydrogenation. V. A Synthesis of Fluoranthene. J. Am. Chem. Soc. 1947;69(3):505–509. doi: 10.1021/JA01195A009. doi: 10.1021/ja01195a009. DOI

Mallada B. de la Torre B. Medieta-Moreno J. I. Nachtigallová D. Matěj A. Matoušek M. Mutombo P. Brabec J. Veis L. Cadart T. Kotora M. Jelínek P. On-Surface Strain-Driven Synthesis of Nonalternant Non-Benzenoid Aromatic Compounds Containing Four-to Eight-Membered Rings. J. Am. Chem. Soc. 2021;143(36):14694–14702. doi: 10.1021/jacs.1c06168. doi: 10.1021/jacs.1c06168. PubMed DOI

Mallada B. Chen Q. Chutora T. Sánchez-Grande A. Cirera B. Santos J. Martín N. Ecija D. Jelínek P. de la Torre B. Resolving Atomic-Scale Defects in Conjugated Polymers On-Surfaces. Chem.–Eur. J. 2022;28(48):e202200944. doi: 10.1002/CHEM.202200944. doi: 10.1002/chem.202200944. PubMed DOI

Márquez I. R. Ruíz Del Árbol N. Urgel J. I. Villalobos F. Fasel R. López M. F. Cuerva J. M. Martín-Gago J. A. Campaña A. G. Sánchez-Sánchez C. On-Surface Thermal Stability of a Graphenic Structure Incorporating a Tropone Moiety. Nanomaterials. 2022;12(3):488. doi: 10.3390/NANO12030488. doi: 10.3390/nano12030488. PubMed DOI PMC

Sánchez-Sánchez C. Dienel T. Nicolaï A. Kharche N. Liang L. Daniels C. Meunier V. Liu J. Feng X. Müllen K. Sánchez-Valencia J. R. Gröning O. Ruffieux P. Fasel R. On-Surface Synthesis and Characterization of Acene-Based Nanoribbons Incorporating Four-Membered Rings. Chem.–Eur. J. 2019;25(52):12074–12082. doi: 10.1002/CHEM.201901410. doi: 10.1002/chem.201901410. PubMed DOI

Liu M. Liu M. She L. Zha Z. Pan J. Li S. Li T. He Y. Cai Z. Wang J. Zheng Y. Qiu X. Zhong D. Graphene-like Nanoribbons Periodically Embedded with Four- and Eight-Membered Rings. Nat. Commun. 2017;8(1):1–7. doi: 10.1038/ncomms14924. doi: 10.1002/chem.201605561. PubMed DOI PMC

Fan Q. Martin-Jimenez D. Ebeling D. Krug C. K. Brechmann L. Kohlmeyer C. Hilt G. Hieringer W. Schirmeisen A. Gottfried J. M. Nanoribbons with Nonalternant Topology from Fusion of Polyazulene: Carbon Allotropes beyond Graphene. J. Am. Chem. Soc. 2019;141(44):17713–17720. doi: 10.1021/jacs.9b08060. doi: 10.1021/jacs.9b08060. PubMed DOI

Deyerling J. Pörtner M. Đorđević L. Riss A. Bonifazi D. Auwärter W. On-Surface Synthesis of Rigid Benzenoid- and Nonbenzenoid-Coupled Porphyrin–Graphene Nanoribbon Hybrids. J. Phys. Chem. C. 2022;126(19):8467–8476. doi: 10.1021/ACS.JPCC.2C00912. doi: 10.1021/acs.jpcc.2c00912. DOI

Di Giovannantonio M. Urgel J. I. Beser U. Yakutovich A. V. Wilhelm J. Pignedoli C. A. Ruffieux P. Narita A. Müllen K. Fasel R. On-Surface Synthesis of Indenofluorene Polymers by Oxidative Five-Membered Ring Formation. J. Am. Chem. Soc. 2018;140(10):3532–3536. doi: 10.1021/JACS.8B00587. doi: 10.1021/jacs.8b00587. PubMed DOI

Liu M. Liu M. Zha Z. Pan J. Qiu X. Li T. Wang J. Zheng Y. Zhong D. Thermally Induced Transformation of Nonhexagonal Carbon Rings in Graphene-like Nanoribbons. J. Phys. Chem. C. 2018;122(17):9586–9592. doi: 10.1021/ACS.JPCC.8B02565. doi: 10.1021/acs.jpcc.8b02565. DOI

Urgel J. I. Bock J. Di Giovannantonio M. Ruffieux P. Pignedoli C. A. Kivala M. Fasel R. On-Surface Synthesis of π-Conjugated Ladder-Type Polymers Comprising Nonbenzenoid Moieties. RSC Adv. 2021;11(38):23437–23441. doi: 10.1039/D1RA03253D. doi: 10.1039/D1RA03253D. PubMed DOI PMC

Hou I. C.-Y. Sun Q. Eimre K. Di Giovannantonio M. Urgel J. I. Ruffieux P. Narita A. Fasel R. Müllen K. On-Surface Synthesis of Unsaturated Carbon Nanostructures with Regularly Fused Pentagon-Heptagon Pairs. J. Am. Chem. Soc. 2020;142(23):10291–10296. doi: 10.1021/JACS.0C03635. doi: 10.1021/jacs.0c03635. PubMed DOI PMC

Gao H.-Y. Wagner H. Zhong D. Franke J.-H. Studer A. Fuchs H. Glaser Coupling at Metal Surfaces. Angew. Chem., Int. Ed. 2013;52(14):4024–4028. doi: 10.1002/ANIE.201208597. doi: 10.1002/anie.201208597. PubMed DOI

de la Torre B. Matěj A. Sánchez-Grande A. Cirera B. Mallada B. Rodríguez-Sánchez E. Santos J. Mendieta-Moreno J. I. Edalatmanesh S. Lauwaet K. Otyepka M. Medveď M. Buendía Á. Miranda R. Martín N. Jelínek P. Écija D. Tailoring π-Conjugation and Vibrational Modes to Steer on-Surface Synthesis of Pentalene-Bridged Ladder Polymers. Nat. Commun. 2020;11(1):4567. doi: 10.1038/s41467-020-18371-2. doi: 10.1038/s41467-020-18371-2. PubMed DOI PMC

Yang B. Lin H. Miao K. Zhu P. Liang L. Sun K. Zhang H. Fan J. Meunier V. Li Y. Li Q. Chi L. Catalytic Dealkylation of Ethers to Alcohols on Metal Surfaces. Angew. Chem. 2016;128(34):10035–10039. doi: 10.1002/ANGE.201602414. doi: 10.1002/ange.201602414. PubMed DOI

Krüger J. García F. Eisenhut F. Skidin D. Alonso J. M. Guitián E. Pérez D. Cuniberti G. Moresco F. Peña D. Decacene: On-Surface Generation. Angew. Chem., Int. Ed. 2017;56(39):11945–11948. doi: 10.1002/ANIE.201706156. doi: 10.1002/anie.201706156. PubMed DOI

Fudickar W. Linker T. Why Triple Bonds Protect Acenes from Oxidation and Decomposition. J. Am. Chem. Soc. 2012;134(36):15071–15082. doi: 10.1021/JA306056X. doi: 10.1021/ja306056x. PubMed DOI

Gao H.-Y. Held P. A. Amirjalayer S. Liu L. Timmer A. Schirmer B. Díaz Arado O. Mönig H. Mück-Lichtenfeld C. Neugebauer J. Studer A. Fuchs H. Intermolecular On-Surface σ-Bond Metathesis. J. Am. Chem. Soc. 2017;139(20):7012–7019. doi: 10.1021/JACS.7B02430. doi: 10.1021/jacs.7b02430. PubMed DOI

Sánchez-Grande A. de la Torre B. Santos J. Cirera B. Lauwaet K. Chutora T. Edalatmanesh S. Mutombo P. Rosen J. Zbořil R. Miranda R. Björk J. Jelínek P. Martín N. Écija D. On-Surface Synthesis of Ethynylene-Bridged Anthracene Polymers. Angew. Chem. 2019;131(20):6631–6635. doi: 10.1002/ANGE.201814154. doi: 10.1002/ange.201814154. PubMed DOI PMC

Sun Q. Yu X. Bao M. Liu M. Pan J. Zha Z. Cai L. Ma H. Yuan C. Qiu X. Xu W. Direct Formation of C–C Triple-Bonded Structural Motifs by On-Surface Dehalogenative Homocouplings of Tribromomethyl-Substituted Arenes. Angew. Chem., Int. Ed. 2018;57(15):4035–4038. doi: 10.1002/ANIE.201801056. doi: 10.1002/anie.201801056. PubMed DOI

Cioslowski J. Schimeczek M. Piskorz P. Moncrieff D. Thermal Rearrangement of Ethynylarenes to Cyclopenta fused Polycyclic Aromatic Hydrocarbons: An Electronic Structure Study. J. Am. Chem. Soc. 1999;121(15):3773–3778. doi: 10.1021/JA9836601. doi: 10.1021/ja9836601. DOI

Gross L. Mohn F. Moll N. Liljeroth P. Meyer G. The Chemical Structure of a Molecule Resolved by Atomic Force Microscopy. Science. 2009;325(5944):1110–1114. doi: 10.1126/science.1176210. doi: 10.1126/science.1176210. PubMed DOI

Lowe B. Hellerstedt J. Matěj A. Mutombo P. Kumar D. Ondráček M. Jelinek P. Schiffrin A. Selective Activation of Aromatic C-H Bonds Catalyzed by Single Gold Atoms at Room Temperature. J. Am. Chem. Soc. 2022;144(46):21389–21397. doi: 10.1021/jacs.2c10154. doi: 10.1021/jacs.2c10154. PubMed DOI

Gilmore K. Alabugin I. V. Cyclizations of Alkynes: Revisiting Baldwins Rules for Ring Closure. Chem. Rev. 2011;111(11):6513–6556. doi: 10.1021/CR200164Y. doi: 10.1021/cr200164y. PubMed DOI

Zhang Y.-Q. Kepčija N. Kleinschrodt M. Diller K. Fischer S. Papageorgiou A. C. Allegretti F. Björk J. Klyatskaya S. Klappenberger F. Ruben M. Barth J. V. Homo-Coupling of Terminal Alkynes on a Noble Metal Surface. Nat. Commun. 2012;3(1):1–8. doi: 10.1038/ncomms2291. PubMed DOI

Sen D. Błoński P. de la Torre B. Jelínek P. Otyepka M. Thermally Induced Intra-Molecular Transformation and Metalation of Free-Base Porphyrin on Au(111) Surface Steered by Surface Confinement and Ad-Atoms. Nanoscale Adv. 2020;2(7):2986–2991. doi: 10.1039/D0NA00401D. doi: 10.1039/D0NA00401D. PubMed DOI PMC

Glidewell C. Lloyd D. Mndo Study of Bond Orders in Some Conjugated BI- and Tri-Cyclic Hydrocarbons. Tetrahedron. 1984;40(21):4455–4472. doi: 10.1016/S0040-4020(01)98821-0. doi: 10.1016/S0040-4020(01)98821-0. DOI

Gross L. Mohn F. Moll N. Schuler B. Criado A. Guitián E. Peña D. Gourdon A. Meyer G. Bond-Order Discrimination by Atomic Force Microscopy. Science. 2012;337(6100):1326–1329. doi: 10.1126/science.1225621. doi: 10.1126/science.1225621. PubMed DOI

Kertesz M. Choi C. H. Yang S. Conjugated Polymers and Aromaticity. Chem. Rev. 2005;105(10):3448–3481. doi: 10.1021/CR990357P. doi: 10.1021/cr990357p. PubMed DOI

Schleyer P. V. R. Maerker C. Dransfeld A. Jiao H. van Eikema Hommes N. J. Nucleus-Independent Chemical Shifts: A Simple and Efficient Aromaticity Probe. J. Am. Chem. Soc. 1996;118(26):6317–6318. doi: 10.1021/JA960582D. doi: 10.1021/ja960582d. PubMed DOI

Geuenich D. Hess K. Köhler F. Herges R. Anisotropy of the Induced Current Density (ACID), a General Method To Quantify and Visualize Electronic Delocalization. Chem. Rev. 2005;105(10):3758–3772. doi: 10.1021/cr0300901. doi: 10.1021/cr0300901. PubMed DOI

Cohen A. J. Mori-Sánchez P. Yang W. Insights into Current Limitations of Density Functional Theory. Science. 2008;321(5890):792–794. doi: 10.1126/SCIENCE.1158722. doi: 10.1126/science.1158722. PubMed DOI

Neaton J. B. Hybertsen M. S. Louie S. G. Renormalization of Molecular Electronic Levels at Metal-Molecule Interfaces. Phys. Rev. Lett. 2006;97(21):216405. doi: 10.1103/PHYSREVLETT.97.216405. doi: 10.1103/PhysRevLett.97.216405. PubMed DOI

Li G. Zhu R. Yang Y. Polymer Solar Cells. Nat. Photonics. 2012;6:153–161. doi: 10.1038/nphoton.2012.11. doi: 10.1038/nphoton.2012.11. DOI

Janssen R. A. J. Nelson J. Factors Limiting Device Efficiency in Organic Photovoltaics. Adv. Mater. 2013;25(13):1847–1858. doi: 10.1002/adma.201202873. doi: 10.1002/adma.201202873. PubMed DOI

Zhao Y. Guo Y. Liu Y. 25th Anniversary Article: Recent Advances in n-Type and Ambipolar Organic Field-Effect Transistors. Adv. Mater. 2013;25(38):5372–5391. doi: 10.1002/adma.201302315. doi: 10.1002/adma.201302315. PubMed DOI