Flavins are known to be extremely versatile, thus enabling routes to innumerable modifications in order to obtain desired properties. Thus, in the present paper, the group of bio-inspired conjugated materials based on the alloxazine core is synthetized using two efficient novel synthetic approaches providing relatively high reaction yields. The comprehensive characterization of the materials, in order to evaluate the properties and application potential, has shown that the modification of the initial alloxazine core with aromatic substituents allows fine tuning of the optical bandgap, position of electronic orbitals, absorption and emission properties. Interestingly, the compounds possess multichromophoric behavior, which is assumed to be the results of an intramolecular proton transfer.

Faculty of Chemistry Materials Research Centre Brno University of Technology Purkyňova 118 612 00 Brno Czech Republic

Linz Institute for Organic Solar Cells Physical Chemistry Johannes Kepler University Linz Altenbergerstraße 69 4040 Linz Austria

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Glowacki E.D., Tangorra R.R., Coskun H., Farka D., Operamolla A., Kanbur Y., Milano F., Giotta L., Farinola G.M., Sariciftci N.S. Bioconjugation of hydrogen-bonded organic semiconductors with functional proteins. J. Mater. Chem. C. 2015;3:6554–6564. doi: 10.1039/C5TC00556F. DOI

Simon D.T., Gabrielsson E.O., Tybrandt K., Berggren M. Organic Bioelectronics: Bridging the Signaling Gap between Biology and Technology. Chem. Rev. 2016;116:13009–13041. doi: 10.1021/acs.chemrev.6b00146. PubMed DOI

Zhang S.-F., Chen X.-K., Fan J.-X., Ren A.-M. Rational design of bio-inspired high-performance ambipolar organic semiconductor materials based on indigo and its derivatives. Org. Electron. 2015;24:12–25. doi: 10.1016/j.orgel.2015.05.021. DOI

Cipriano T., Knotts G., Laudari A., Bianchi R.C., Alves W.A., Guha S. Bioinspired Peptide Nanostructures for Organic Field-Effect Transistors. ACS Appl. Mater. Interfaces. 2014;6:21408–21415. doi: 10.1021/am5064124. PubMed DOI

Barbarella G., di Maria F. Supramolecular Oligothiophene Microfibers Spontaneously Assembled on Surfaces or Coassembled with Proteins inside Live Cells. Acc. Chem. Res. 2015;48:2230–2241. doi: 10.1021/acs.accounts.5b00241. PubMed DOI

Ekiz M.S., Cinar G., Khalily M.A., Guler M.O. Self-assembled peptide nanostructures for functional materials. Nanotechnology. 2016;27:402002. doi: 10.1088/0957-4484/27/40/402002. PubMed DOI

Jürgensen N., Ackermann M., Marszalek T., Zimmermann J., Morfa A.J., Pisula W., Bunz U.H.F., Hinkel F., Hernandez-Sosa G. Solution-Processed Bio-OLEDs with a Vitamin-Derived Riboflavin Tetrabutyrate Emission Layer. ACS Sustain. Chem. Eng. 2017;5:5368–5372. doi: 10.1021/acssuschemeng.7b00675. DOI

Minami T., Sato T., Minamiki T., Tokito S. An extended-gate type organic FET based biosensor for detecting biogenic amines in aqueous solution. Anal. Sci. 2015;31:721–724. doi: 10.2116/analsci.31.721. PubMed DOI

Minami T., Sato T., Minamiki T., Fukuda K., Kumaki D., Tokito S. A novel OFET-based biosensor for the selective and sensitive detection of lactate levels. Biosens. Bioelectron. 2015;74:45–48. doi: 10.1016/j.bios.2015.06.002. PubMed DOI

Hardy J.G., Amend M.N., Geissler S., Lynch V.M., Schmidt C.E. Peptide-directed assembly of functional supramolecular polymers for biomedical applications: Electroactive molecular tongue-twisters (oligoalanine-oligoaniline-oligoalanine) for electrochemically enhanced drug delivery. J. Mater. Chem. B. 2015;3:5005–5009. doi: 10.1039/C5TB00106D. PubMed DOI

Tybrandt K., Forchheimer R., Berggren M. Logic gates based on ion transistors. Nat. Commun. 2012;3:871. doi: 10.1038/ncomms1869. PubMed DOI

Ramses V.M., Jamie L.B., Carina R.F., Jin L., Robert F.S., Rui M.D.N., Suo Z., George M.W. Robotic Tentacles with Three-Dimensional Mobility Based on Flexible Elastomers. Adv. Mater. 2012;25:205–212. PubMed

Yang D., Mohit S.V., So J.H., Mosadegh B., Keplinger C., Lee B., Khashai F., Lossner E., Suo Z., George M.W. Buckling Pneumatic Linear Actuators Inspired by Muscle. Adv. Mater. Technol. 2016;1:1–6. doi: 10.1002/admt.201600055. DOI

Irimia-Vladu M., Pavel A.T., Reisinger M., Shmygleva L., Kanbur Y., Schwabegger G., Bodea M., Schwödiauer R., Mumyatov A., Jeffrey W.F., et al. Biocompatible and Biodegradable Materials for Organic Field-Effect Transistors. Adv. Funct. Mater. 2010;20:4069–4076. doi: 10.1002/adfm.201001031. DOI

Christopher J.B., Bao Z. Organic Thin-Film Transistors Fabricated on Resorbable Biomaterial Substrates. Adv. Mater. 2009;22:651–655. PubMed PMC

Tao H., Mark A.B., Yang M., Zhang J., Liu M., Sean M.S., Richard D.A., Manu S.M., Michael C.M., John A.R., et al. Silk-Based Conformal, Adhesive, Edible Food Sensors. Adv. Mater. 2012;24:1067–1072. doi: 10.1002/adma.201103814. PubMed DOI

Sandro G., Vincent M. Mechanisms of flavoprotein-catalyzed reactions. Eur. J. Biochem. 1989;181:1–17. PubMed

Cuello A.O., McIntosh C.M., Rotello V.M. Model Systems for Flavoenzyme Activity. The Role of N(3)-H Hydrogen Bonding in Flavin Redox Processes. J. Am. Chem. Soc. 2000;122:3517–3521. doi: 10.1021/ja994204v. DOI

Kurisu G., Kusunoki M., Katoh E., Yamazaki T., Teshima K., Onda Y., Kimata-Ariga Y., Hase T. Structure of the electron transfer complex between ferredoxin and ferredoxin-NADP+ reductase. Nat. Struct. Biol. 2001;8:117–121. doi: 10.1038/84097. PubMed DOI

Joosten V., van Berkel W.J.H. Flavoenzymes. Curr. Opin. Chem. Biol. 2007;11:195–202. doi: 10.1016/j.cbpa.2007.01.010. PubMed DOI

Miura R. Versatility and specificity in flavoenzymes: Control mechanisms of flavin reactivity. Chem. Rec. 2001;1:183–194. doi: 10.1002/tcr.1007. PubMed DOI

Kakkar P., Singh B. Mitochondria: A hub of redox activities and cellular distress control. Mol. Cell. Biochem. 2007;305:235–253. doi: 10.1007/s11010-007-9520-8. PubMed DOI

Lee M., Hong J., Seo D.H., Dong H.N., Ki T.N., Kang K., Chan B.P. Redox Cofactor from Biological Energy Transduction as Molecularly Tunable Energy-Storage Compound. Angew. Chem. Int. Ed. 2013;52:8322–8328. doi: 10.1002/anie.201301850. PubMed DOI

Hong J., Lee M., Lee B., Seo D.-H., Park C.B., Kang K. Biologically inspired pteridine redox centres for rechargeable batteries. Nat. Commun. 2014;5:5335. doi: 10.1038/ncomms6335. PubMed DOI

Orita A., Verde M.G., Sakai M., Meng Y.S. A biomimetic redox flow battery based on flavin mononucleotide. Nat. Commun. 2016;7:13230. doi: 10.1038/ncomms13230. PubMed DOI PMC

Lin K., Gómez-Bombarelli R., Beh E.S., Tong L., Chen Q., Valle A., Aspuru-Guzik A., Aziz M.J., Gordon R.G. A redox-flow battery with an alloxazine-based organic electrolyte. Nat. Energy. 2016;1:16102. doi: 10.1038/nenergy.2016.102. DOI

Pauszek R.F., Kodali G., Caldwell S.T., Fitzpatrick B., Zainalabdeen N.Y., Cooke G., Rotello V.M., Stanley R.J. Excited State Charge Redistribution and Dynamics in the Donor-π-Acceptor Flavin Derivative ABFL. J. Phys. Chem. B. 2013;117:15684–15694. doi: 10.1021/jp406420h. PubMed DOI

Legrand Y.-M., Gray M., Cooke G., Rotello V.M. Model Systems for Flavoenzyme Activity: Relationships between Cofactor Structure, Binding and Redox Properties. J. Am. Chem. Soc. 2003;125:15789–15795. doi: 10.1021/ja036940b. PubMed DOI

Jortner J., Ratner M.A. Molecular Electronics. Blackwell; Oxford, UK: 1997.

Carter F.L., Siatkowski R.F., Wohltjen J. Molecular Electronic Devices. Elsevier; Amsterdam, The Netherlands: 1988.

Akiyama T., Simeno F., Murakami M., Yoneda F. Flavin-6-carboxylic acids as novel and simple flavoenzyme models. Nonenzymatic stabilization of the flavin semiquinone radical and the 4a-hydroperoxyflavin by intramolecular hydrogen bonding. J. Am. Chem. Soc. 1992;114:6613–6620. doi: 10.1021/ja00043a002. DOI

Zoltowski D., Nash A.I., Gardner K.H. Variations in Protein-Flavin Hydrogen Bonding in a Light, Oxygen, Voltage Domain Produce Non-Arrhenius Kinetics of Adduct Decay. Biochemistry. 2011;50:8771–8779. doi: 10.1021/bi200976a. PubMed DOI PMC

Gozem S., Mirzakulova E., Schapiro I., Melaccio F., Glusac K.D., Olivucci M. Conical Intersection Controls the Deactivation of the Bacterial Luciferase Fluorophore. Angew. Chem. Int. Ed. 2014;53:9870–9875. doi: 10.1002/anie.201404011. PubMed DOI

Szymański M., Maciejewski A., Steer R.P. Photophysics of thione triplets in solution: Factors controlling the rates of radiationless decay. Chem. Phys. 1988;124:143–154. doi: 10.1016/0301-0104(88)85090-0. DOI

Nandwana V., Samuel I., Cooke G., Rotello V.M. Aromatic stacking interactions in flavin model systems. Acc. Chem. Res. 2013;46:1000–1009. doi: 10.1021/ar300132r. PubMed DOI

Prongjit M., Sucharitakul J., Palfey B.A., Chaiyen P. Oxidation mode of pyranose 2-oxidase is controlled by pH. Biochemistry. 2013;52:1437–1445. doi: 10.1021/bi301442x. PubMed DOI PMC

Marian C.M., Nakagawa S., Rai-Constapel V., Karasulu B., Thiel W. Photophysics of flavin derivatives absorbing in the blue-green region: Thioflavins as potential cofactors of photoswitches. J. Phys. Chem. B. 2014;118:1743–1753. doi: 10.1021/jp4098233. PubMed DOI

Kramer R.H., Fortin D.L., Trauner D. New photochemical tools for controlling neuronal activity. Curr. Opin. Neurobiol. 2009;19:544–552. doi: 10.1016/j.conb.2009.09.004. PubMed DOI PMC

Mataranga-Popa L.N., Torje I., Ghosh T., Leitl M.J., Spath A., Novianti M.L., Webster R.D., Konig B. Synthesis and electronic properties of π-extended flavins. Org. Biomol. Chem. 2015;13:10198–10204. doi: 10.1039/C5OB01418B. PubMed DOI

Sakai K., Nagahara K., Yoshii Y., Hoshino N., Akutagawa T. Structural and Spectroscopic Study of 6,7-Dicyano-Substituted Lumazine with High Electron Affinity and Proton Acidity. J. Phys. Chem. A. 2013;117:3614–3624. doi: 10.1021/jp401528c. PubMed DOI

Salzmann S., Marian C.M. The photophysics of alloxazine: A quantum chemical investigation in vacuum and solution. Photochem. Photobiol. Sci. 2009;8:1655–1666. doi: 10.1039/b9pp00022d. PubMed DOI

Chang X.-P., Xie X.-Y., Lin S.-Y., Cui G. QM/MM Study on Mechanistic Photophysics of Alloxazine Chromophore in Aqueous Solution. J. Phys. Chem. A. 2016;120:6129–6136. doi: 10.1021/acs.jpca.6b02669. PubMed DOI

Cain C.K., Mallette M.F., Taylor E.C. Pyrimido[4,5-b]pyrazines. I. Synthesis of 6,7-symmetrically substituted derivatives. J. Am. Chem. Soc. 1946;68:1996–1999. doi: 10.1021/ja01214a036. PubMed DOI

Wen L., Rasmussen S. Synthesis of thieno[3,4-b]pyrazine oligomers as precursors to low band gap materials and models of effective conjugation. Polym. Prepr. 2007;48:132–133.

Nietfeld J.P., Schwiderski R.L., Gonnella T.P., Rasmussen S.C. Structural Effects on the Electronic Properties of Extended Fused-Ring Thieno[3,4-b]pyrazine Analogues. J. Org. Chem. 2011;76:6383–6388. doi: 10.1021/jo200850w. PubMed DOI

Chen S., Hossain M.S., Foss F.W. Organocatalytic Dakin Oxidation by Nucleophilic Flavin Catalysts. Org. Lett. 2012;14:2806–2809. doi: 10.1021/ol3010326. PubMed DOI

Vinot N. Synthesis of 2,4-dihydropteridines substituted in the 6 and 7 positions. C. R. Acad. Sci. Paris Ser. C. 1968;266:1104–1106.

Zina A.A.A., Najwa M.J.A., Zeenah W.A., Najim A.A. Synthesis and Biological Evaluation of New Dipyridylpteridines, Lumazines, and Related Analogues. J. Heterocyclic Chem. 2016;54:895–903.

Tajbakhsh M., Bakooie H., Ghassemzadeh M., Heravi M. A new general and regioselective method for the synthesis of 6,7-disubstituted lumazines. Indian J. Heterocycl. Chem. 2000;9:235–236.

Ram V., Knappe W.R., Pfleiderer W. Synthesis and photochemistry of N-8 substituted lumazines. Tetrahedron Lett. 1977;18:3795–3798. doi: 10.1016/S0040-4039(01)83356-6. DOI

Strakhov A.V., Pushkareva Z.V. Heterocyclic N-oxides. IX. Preparation and properties of some heterocyclic N-oxides with condensed rings. Tr. Ural. Politekh. Inst. im. S. M. Kirova. 1960:34–44.

Holmgren A.V., Wenner W. Alloxan monohydrate. Org. Synth. 1952;32:6–7.

Hu J., Zhang D., Harris F.W. Ruthenium(III) Chloride Catalyzed Oxidation of Pyrene and 2,7-Disubstituted Pyrenes: An Efficient, One-Step Synthesis of Pyrene-4,5-diones and Pyrene-4,5,9,10-tetraones. J. Org. Chem. 2005;70:707–708. doi: 10.1021/jo048509q. PubMed DOI

Hartung W.H. Catalytic reduction of nitriles and oximes. J. Am. Chem. Soc. 1928;50:3370–3374. doi: 10.1021/ja01399a033. DOI

Abdolmaleki A., Malek-Ahmadi S. A partially water-soluble cationic Mn(III)-salphen complex for catalytic epoxidation. Can. J. Chem. 2011;89:1202–1206. doi: 10.1139/v11-094. DOI

Joshi S.C., Mehrotra K.N. A new synthesis of pyrazines. Indian J. Chem. Sect. B. 1983;22B:396–397.

Song Y., Wang Q., Ding Z., Tao F. Synthesis of hydroxycedranone and aminohydroxycedrane. Synth. Commun. 1999;29:4171–4178. doi: 10.1080/00397919908085890. DOI

Xiao J., Xiao X., Zhao Y., Wu B., Liu Z., Zhang X., Wang S., Zhao X., Liu L., Jiang L. Synthesis, physical properties and self-assembly behavior of azole-fused pyrene derivatives. Nanoscale. 2013;5:5420–5425. doi: 10.1039/c3nr00523b. PubMed DOI

Alanine A., Buettelmann B., Heitz N.M.-P., Pinard E., Wyler R.F. Preparation of Phenylalkylaminocyclohexylphenols and Related Compounds as NMDA Receptor Blockers. 6,184,236 B1. U.S. Patent. 2001

Mamada M., Pérez-Bolívar C., Kumaki D., Nina A.E., Tokito S., Anzenbacher P. Benzimidazole Derivatives: Synthesis, Physical Properties, and n-Type Semiconducting Properties. Chem. Eur. J. 2014;20:11835–11846. doi: 10.1002/chem.201403058. PubMed DOI

Chung S.-K., Lee K.-W., Kang H.I., Yamashita C., Kudo M., Yoshida Y. Design and synthesis of potential inhibitors of the ergosterol biosynthesis as antifungal agents. Bioorg. Med. Chem. 2000;8:2475–2486. doi: 10.1016/S0968-0896(00)00177-2. PubMed DOI

Wang X., Silverman R.B. Monoamine oxidase-catalyzed oxidation of endo,endo-2-amino-6-[(Z)-2′-phenyl]ethenylbicyclo[2.2.1]heptane, a potential probe for a radical cation intermediate. Bioorg. Med. Chem. 2000;8:1645–1651. doi: 10.1016/S0968-0896(00)00094-8. PubMed DOI

Shearer J.M., Rokita S.E. Diamine preparation for synthesis of a water soluble Ni(II) salen complex. Bioorg. Med. Chem. Lett. 1999;9:501–504. doi: 10.1016/S0960-894X(99)00020-7. PubMed DOI

Dalton S.R., Glazier S., Leung B., Win S., Megatulski C., Burgmayer S.J.N. DNA binding by Ru(II)–bis(bipyridine)–pteridinyl complexes. J. Biol. Inorg. Chem. 2008;13:1133–1148. doi: 10.1007/s00775-008-0399-y. PubMed DOI

Sherman W.R., Taylor E.C., Jr. Diaminouracil hydrochloride. Org. Synth. 1957;37:15–17.

Chang K.L., Mi S.K., Jin S.G., In-Sook H.L. Benzoin condensation reactions of 5-membered heterocyclic compounds. J. Heterocyclic Chem. 1992;29:149–153.

Tyagi A., Penzkofer A. Absorption and emission spectroscopic characterization of lumichrome in aqueous solutions. Photochem. Photobiol. 2010;87:524–533. doi: 10.1111/j.1751-1097.2010.00836.x. PubMed DOI

Wei X., Pan W., Duan W., Hollas A., Yang Z., Li B., Nie Z., Liu J., Reed D., Wang W., et al. Materials and Systems for Organic Redox Flow Batteries: Status and Challenges. ACS Energy Lett. 2017;2:2187–2204. doi: 10.1021/acsenergylett.7b00650. DOI

Petering H.G., van Giessen G.J. 8-Chloroalloxazine, A New Diuretic. Synthesis and Structure. J. Org. Chem. 1961;26:2818–2821. doi: 10.1021/jo01066a047. DOI

Ross W.C.J. Lipoid-soluble alloxazine derivatives. J. Chem. Soc. 1948:219–224. doi: 10.1039/jr9480000219. PubMed DOI

Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb M.A., Cheeseman J.R., Scalmani G., Barone V., Petersson G.A., Nakatsuji H., et al. Gaussian 09, Revision A.02. Gaussian, Inc.; Wallingford, CT, USA: 2016.

Nature-Inspired Photocatalytic Hydrogen Production with a Flavin Photosensitizer

Tunable Properties of Nature-Inspired N,N'-Alkylated Riboflavin Semiconductors