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COMMUNICATION J. Fraser Stoddart et al. Directed self-assembly of a ring-in-ring complex
FEATURE ARTICLE Wenbin Lin et al. Hybrid nanomaterials for biomedical applications
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NIR-fluorescent coumarin-fused BODIPY dyes with large Stokes shifts Andrei Y. Bochkov,*a‡ Igor O. Akchurin,a‡ Oleg A. Dyachenkob and Valery F. Travena
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A series of novel non-symmetrical coumarin-fused BODIPY dyes were synthesised. Their absorption and emission properties are strongly influenced by substitution in coumarin moiety. Diethylamino-substituted dyes showed near-IR emission with large Stokes shifts (up to 144 nm) and good fluorescence quantum yields. 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives are fluorescent dyes having many advantages over other classes of dyes, namely high extinction and fluorescence quantum yields which are usually weakly affected by solvent polarity, sharp absorption and emission bands, excellent photo- and chemical stability. 1 Because of their outstanding properties BODIPYs are considered as dyes of choice for many applications, such as fluorescent sensors, 2 fluorescent labeling of biomolecules and fluorescent imaging of cells,3 photodynamic therapy, 4 laser dyes,5 photovoltaics,6 lightemitting devices7 etc. For some applications, in particular biochemical, large Stokes shifts and near-IR fluorescence are highly desirable, but classical BODIPYs absorb light in the range of 500–600 nm and have rather small Stokes shifts (15– 30 nm). To address these issues a number of approaches have been reported. Extension of the π-conjugation by fusion of various aryl cycles to BODIPY core is being extensively developed in recent years. A variety of BODIPY dyes have been prepared starting from fused pyrroles, such as benzofuro[3,2-b]pyrrole and thianaphtheno[3,2-b]pyrrole,8 furo[3,2-b]pyrrole,9 thieno[3,2-b]pyrrole,10 1,4,5,5atetrahydrochromeno[2,3-g]indole, 11 isoindole,12 2Hdibenzo[e,g]isoindole,13 fluoranthro[8,9-f]isoindole,14 indole,15 and benzo[1,2-b:5,4-b']dipyrrole. 15b Alternatively aryl annulations were performed by oxidative cyclodehydrogenation of BODIPYs having electron-rich aryl substituents to give anthracene-, perylene- or phenanthrenefused systems.16 We suggested that annulation of coumarin unit to BODIPY core would shift emission to the red region and Stokes shifts of resulting dyes are likely to be higher compared to typical non-annulated BODIPYs. Coumarin derivatives represent a unique class of fluorescent dyes, exhibiting high fluorescence quantum yields and large Stokes shifts.17 An example of successful coumarin-fusion approach was published recently when this manuscript was in preparation. Wang et al. reported synthesis of dyes having coumarin- and rhodamine-fused conjugated skeleton, which exhibited emission in the deep red This journal is © The Royal Society of Chemistry [year]
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Scheme 1 Synthetic route to coumarin-fused BODIPY dyes. Reagents and conditions: (a) DMF, POCl3, 60–84 %; (b) Ph3P=CHBz, DCM, RT, 24 h, 55–93 %; (c) NaN3, acetone, 85–88 %; (d) toluene, reflux, 1 h, 67– 96 %; (e) i: POCl3, DCM, RT; ii: TEA; iii: BF3×OEt2, 30–58 %.
region with large Stokes shift.18 Herein we report synthesis and spectral study of nonsymmetrical BODIPY dyes 1 having 7-substituted chromeno[4,3-b]pyrrol-4-one and alkylpyrrole as pyrromethene-forming units. Compounds 1c-d bearing diethylamino donor in coumarin moiety exhibit NIR emission and large Stokes shifts. Synthetic route to coumarin-fused BODIPYs is shown in Scheme 1. The key BODIPY precursors 2benzoylchromeno[4,3-b]pyrrol-4-ones 6 were prepared using novel approach developed by us. Preparation of some 3acylchromeno[4,3-b]pyrrol-4-ones by cyclocondensation of chloroaldehyde 3a with α-aminoketones was reported in literature, but presence of two reactive functions (chloro- and formyl-) caused side reactions and considerable by-products formation.19 In our approach these functions are involved in step by step transformations in mild conditions. Firstly, 4hydroxycoumarins were subjected to Vilsmeier reaction to give corresponding 4-chloro-3-formylcoumarins 3. The acylvinyl moiety was constructed using Wittig reaction and then chlorine was substituted by azide-ion. The resulting 4azido-3-(2-benzoylvinyl)coumarins 5 were thermally cyclized to fused pyrroles 6. The above approach affords 2-benzoyl[journal], [year], [vol], 00–00 | 1
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chromeno[4,3-b]pyrrol-4-ones 6a-c in 4 steps starting from 4hydroxycoumarins in high overall yields and may be expanded for preparation of 2-acyl-, 2-carbonyl-, 2-alkyl- and 2-arylchromeno[4,3-b]pyrrol-4-ones as corresponding Wittig reagents are easily available. Finally, desired BODIPY dyes 1a-d were prepared following conventional two-step protocol without isolation of dipyrromethene intermediate. Reactivity of 6a-c turned to be low and formation of dipyrromethene required several days (up to one week) albeit yields of 1a-d were good. The detailed synthetic procedures and compounds characterisation data are given in the ESI.† Single-crystal X-ray diffraction analysis of compound 1c (Fig. 1) revealed high planarity of pentacyclic conjugated skeleton and almost orthogonally rotated phenyl ring (dihedral angle 102.1°). Shortened distances between fluorine atoms and hydrogen atom attached to position 5 (C3) of coumarin fragment seem to be concerned with intramolecular hydrogen bonding. In benzene ring with attached diethylaminosubstituent bonds C2–C3 and C18–C19 are shorter compared with remaining four bonds, and C1–N1 bond is also more akin to a double bond that indicates significant contribution of para-quinoidal resonance state in 7-dialkylaminocoumarins.20 UV-vis absorption and emission properties of coumarinfused BODIPYs were studied in solvents of different polarity (Table 1). Dye 1a with non-substituted coumarin moiety shows two clearly separated absorption bands (Fig. 1): in 300 nm region and narrow band with shoulder and maximum at 516 nm (DCM, ε 3.6×104 M-1×cm-1). Intense emission band maximum is located at 546 nm (φ F 0.66). Stokes shift of 1a in DCM is 1065 cm-1. In higher polarity solvents (MeOH, DMF) absorption bands are slightly blue-shifted, while emisson maximum in MeOH also shifts to blue region for 4 nm and emission maximum in DMF shifts to red region for 5 nm. Absorption and emission properties of 1a are similar to those of 1,3,5,7-tetramethyl-2,6-diethyl-8-phenyl-BODIPY.21 Thus fusion of non-substituted coumarin to BODIPY doesn’t afford longer wavelength absorbing dye. Hydroxy-substituted dye 1b shows red-shifted absorption and emission maxima and higher extinction as compared to 1a. It is noteworthy that fluorescence quantum yield of 1b in polar protic solvent (MeOH) is relatively high (φ F 0.65) while being much lower in polar aprotic solvent (DMF) (φF 0.15).
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Fig. 2 UV-vis absorption (solid) and fluorescence (dashed) spectra of 1a-d in DCM. Table 1 Photophysical properties of coumarin-fused BODIPYs 1. solvent λabs (nm) ε (M-1×cm-1) λem (nm) ∆ν (cm-1) DCM 516 36000 546 1065 MeOH 504 –b 542 1391 DMF 510 29600 551 1459 PhMe 548 52200 578 947 1b DCM 530 46200 567 1231 MeOH 530 49400 579 1597 DMF 538 66800 595 1781 CyH 620 68500 643 577 1c PhMe 632 62700 672 942 DCM 602 59400 697 2264 MeOH 590 46000 720 3060 DMF 606 43900 748 3133 b 642 553 CyH 620 – 1d DCM 606 59100 706 2337 MeOH 594 –b 724 3023 DMF 608 41600 752 3150 8-PhBDPc DCM 524 NA 544 702 compd 1a
φFa 0.66 –b 0.18 0.71 0.64 0.65 0.15 0.86 0.62 0.41 0.06 0.04 –b 0.31 –b 0.03 0.85
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Quantum yields determined with references Rhodamine 6G (1a-b) and Cresyl Violet (1c-d). b Not measured due to very low solubility. c 2,6diethyl-1,3,5,7-tetramethyl-8-phenyl-BODIPY, data from ref. 21.
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Diethylamino-substituted dye 1c expectedly exhibits dramatic bathochromic shift of absorption and emission bands. Since excited states of 7-aminocoumarins have strong intramolecular charge tranfer (ICT) character 20 their absorption and fluorescent charachteristics are strongly dependent on solvent polarity. Absorption of compound 1c shows negative solvatochromism. With increasing solvent polarity its absorption maximum wavelength shifts from 632 nm (toluene) to 590 nm (MeOH). Emission maximum gradually shifts to infra-red region from 643 nm (cyclohexane) to 748 nm (DMF) when solvent polarity increases and fluorescence quantum yields decrease simultaneously. In highly polar solvents (MeOH and DMF) fluorescence is quenched in significant extent (φF 0.06 and 0.04 respectively). One of possible explanations for this may be formation of twisted ICT (TICT) excited state with full charge separation in polar media (positively charged dialkylamino group is rotated orthogonally to the plane of the molecule). In 7-dialkylaminocoumarins TICT excited states are considered to be non-emissive but having non-radiative decay pathway. 22 This journal is © The Royal Society of Chemistry [year]
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Fig. 1 Molecular structure of 1c in the crystal. Selected bond lengths (Å): C1–N1, 1.372; C2–C3, 1.376; C18–C19, 1.377; С3–F1, 3.279(3); Н3–F1, 2.54; С3–F2, 3.019(3); Н3–F2, 2.32.
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Compound 1d was synthesized to examine influence of substitution in alkylpyrrole unit on spectral properties of coumarin-fused BODIPY. Absorption and fluorescence maxima of 1d have slightly longer wavelengths as compared to 1c. This was surprising, because from previously reported data is clear that replacement of 2-ethyl-substituent with hydrogen for symmetrical 23 or non-symmetrical12f BODIPYs causes blue shift of absorption and emission bands of about 20–25 nm. Stokes shifts of BODIPYs 1c-d in polar solvents (MeOH, DMF) are among the highest ever reported for BODIPY derivatives. Most of deep red or near-IR emissive (λem > 650 nm) BODIPYs with large Stokes shifts ( ∆ν > 1500 cm1 15,16a,16b,24 ) suffer from low emission efficiency (φF < 0.1). 3,5-Dioligothienyl-BODIPYs recently reported by Ziessel’s group exhibit NIR-emission with rather large Stokes shifts and moderate quantum yields.25 Coumarin-fused BODIPYs 1c-d showed good balance between Stokes shifts and quantum yields in dichloromethane solutions ( ∆ν 2264–2337 cm-1, φ F 0.31–0.41), which is exceptional for near-IR fluorescent BODIPYs. In summary, a synthetic route to non-symmetrical BODIPYs fused with coumarin was developed. A series of novel dyes with varied substitution both in chromenopyrrole and alkylpyrrole units were prepared and their spectral properties were studied. Coumarin-fused BODIPYs having diethylamino-substitution in coumarin skeleton showed an exceptional photophysical properties combination in moderately polar solvent dichloromethane: intense absorption (5.9×104 M-1×cm-1), near-IR emission (λem 697–706 nm), large Stokes shifts (2264–2337 cm-1, 95–100 nm) and rather high quantum yields (0.31–0.41). In highly polar solvents emission is shifted up to 750 nm affording Stokes shifts as high as 144 nm (3150 cm-1). We consider coumarin-fused BODIPY to be a useful scaffold for design of new efficient NIR-emitting dyes with large Stokes shifts for various applications.
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a Department of Organic Chemistry, Mendeleev University of Chemical Technology, 125047, Miusskaya square 9, Moscow, Russian Federation. E-mail: [email protected]; Fax: +7 495 609 2964. b Institute of Problems of Chemical Physics, 142432, Academician Semenov avenue 1, Chernogolovka, Moscow Region, Russian Federation. † Electronic Supplementary Information (ESI) available: Experimental procedures, charachterization data, UV-vis and fluorescence spectra and X-ray crystallographic data for 1c (CCDC 956947). See DOI: 10.1039/b000000x ‡ These authors contributed equally to this work. 1 (a) A. Loudet and K. Burgess, Chem. Rev., 2007, 107, 4891; (b) G. Ulrich, R. Ziessel and A. Harriman, Angew. Chem. Int. Ed., 2008, 47, 1184. 2 V. Leen and W. Dehaen, Chem. Soc. Rev., 2012, 41, 1130. 3 (a) Y. Gabe, Y. Urano, K. Kikuchi, H. Kojima and T. Nagano, J. Am. Chem. Soc., 2004, 126, 3357; (b) Y. Urano, D. Asanuma, Y. Hama, Y. Koyama, T. Barrett, M. Kamiya, T. Nagano, T. Watanabe, A. Hasegawa, P. L. Choyke and H. Kobayashi, Nature Medicine, 2009, 15, 104; (c) J. Han, A. Loudet, R. Barhoumi, R. C. Burghardt and K. Burgess, J. Am. Chem. Soc., 2009, 131, 1642; (d) D. W. Domaille, L. Zeng and C. J. Chang, J. Am. Chem. Soc., 2010, 132, 1194; (e) A. Matsui, K. Umezawa, Y. Shindo, T. Fujii, D. Citterio, K. Oka and K. Suzuki, Chem. Commun., 2011, 47, 10407.
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A. Kamkaew, S. H. Lim, H. B. Lee, L. V. Kiew, L. Y. Chung and K. Burgess, Chem. Soc. Rev., 2013, 42, 77. (a) F. López Arbeloa, J. Bañuelos, V. Martínez, T. Arbeloa, I. López View Article Online 10.1039/C3CC46498A Arbeloa, International Reviews in PhysicalDOI: Chemistry, 2005, 24, 339; (b) M. Benstead, G. H. Mehl and R. W. Boyle, Tetrahedron, 2011, 67, 3573. (a) T. Rousseau, A. Cravino, T. Bura, G. Ulrich, R. Ziessel and J. Roncali, J. Mater. Chem., 2009, 19, 2298; (b) S. Kolemen, Y. Cakmak, S. Erten-Ela, Y. Altay, J. Brendel, M. Thelakkat and E. U. Akkaya, Org. Lett., 2010, 12, 3812; (c) J.-B. Wang, X.-Q. Fang, X. Pan, S.-Y. Dai and Q.-H. Song, Chem. Asian J., 2012, 7, 696. (d) T. Bura, N. Leclerc, S. Fall, P. Lévêque, T. Heiser, P. Retailleau, S. Rihn, A. Mirloup and R. Ziessel, J. Am. Chem. Soc., 2012, 134, 17404. L. Bonardi, H. Kanaan, F. Camerel, P. Jolinat, P. Retailleau and R. Ziessel, Adv. Funct. Mater., 2008, 18, 401. J. Chen, A. Burghart, A. Derecskei-Kovacs and K. Burgess, J. Org. Chem., 2000, 65, 2900. (a) K. Umezawa, Y. Nakamura, H. Makino, D. Citterio and K. Suzuki, J. Am. Chem. Soc., 2008, 130, 1550; (b) K. Umezawa, A. Matsui, Y. Nakamura, D. Citterio and K. Suzuki, Chem. Eur. J., 2009, 15, 1096. (a) S. G. Awuah, J. Polreis, V. Biradar and Y. You, Org. Lett., 2011, 13, 3884; (b) X.-D. Jiang, H. Zhang, Y. Zhang and W. Zhao, Tetrahedron, 2012, 68, 9795. X.-D. Jiang, R. Gao, Y. Yue, G.-T. Sun and W. Zhao, Org. Biomol. Chem., 2012, 10, 6861. (a) Z. Shen, H. Röhr, K. Rurack, H. Uno, M. Spieles, B. Schulz, G. Reck and N. Ono, Chem. Eur. J., 2004, 10, 4853; (b) S. Goeb and R. Ziessel, Org. Lett., 2007, 9, 737; (c) L. Jiao, C. Yu, M. Liu, Y. Wu, K. Cong, T. Meng, Y. Wang and E. Hao, J. Org. Chem., 2010, 75, 6035; (d) G. Ulrich, S. Goeb, De A. Nicola, P. Retailleau and R. Ziessel, J. Org. Chem., 2011, 76, 4489; (e) T. Uppal, X. Hu, F. R. Fronczek, S. Maschek, P. Bobadova-Parvanova, M. G. H. Vicente, Chem. Eur. J., 2012, 18, 3893; (f) C. Yu, Y. Xu, L. Jiao, J. Zhou, Z. Wang and E. Hao, Chem. Eur. J., 2012, 18, 6437. A. B. Descalzo, H.-J. Xu, Z.-L. Xue, K. Hoffmann, Z. Shen, M. G. Weller, X.-Z. You and K. Rurack, Org. Lett., 2008, 10, 1581. T. Okujima, Y. Tomimori, J. Nakamura, H. Yamada, H. Uno and N. Ono, Tetrahedron, 2010, 66, 6895. (a) Y. Ni, W. Zeng, K.-W. Huang and J. Wu, Chem. Commun., 2013, 49, 1217; (b) A. Wakamiya, T. Murakami and S. Yamaguchi, Chem. Sci., 2013, 4, 1002. (a) C. Jiao, K.-W. Huang and J. Wu, Org. Lett., 2011, 13, 632; (b) L. Zeng, C. Jiao, X. Huang, K.-W. Huang, W.-S. Chin and J. Wu, Org. Lett., 2011, 13, 6026; (c) Y. Hayashi, N. Obata, M. Tamaru, S. Yamaguchi, Y. Matsuo, A. Saeki, S. Seki, Y. Kureishi, S. Saito, S. Yamaguchi and H. Shinokubo, Org. Lett., 2012, 14, 866. (a) Wagner, B. Molecules, 2009, 14, 210; (b) X. Liu, Z. Xu and J. M. Cole, J. Phys. Chem. C, 2013, 117, 16584. J. Chen, W. Liu, B. Zhou, G. Niu, H. Zhang, J. Wu, Y. Wang, W. Ju and P. Wang, J. Org. Chem., 2013, 78, 6121. A. Alberola, L. Calvo, A. González-Ortega, A. P. Encabo, C. M. Sañudo, Synthesis, 2001, 1941. X. Liu, J. M. Cole, P. G. Waddell, T.-C. Lin, J. Radia and A. Zeidler, J. Phys. Chem. A, 2012, 116, 727. T. Chaudhuri, S. Mula, S. Chattopadhyay and M. Banerjee, Spectrochimica Acta A, 2010, 75, 739. Z. R. Grabowski, K. Rotkiewicz and W. Rettig, Chem. Rev., 2003, 103, 3899. M. Kollmannsberger, T. Gareis, S. Heinl, J. Daub and J. Breu, Angew. Chem. Int. Ed., 1997, 36, 1333. A. Martin, C. Long, R. J. Forster and T. E. Keyes, Chem. Commun., 2012, 48, 5617. A. Poirel, De A. Nicola and R. Ziessel, Org. Lett., 2012, 14, 5696.
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Accepted Manuscript This article can be cited before page numbers have been issued, to do this please use: A. Y. Bochkov, I. O. Akchurin, O. A. Dyachenko and V. F. Traven, Chem. Commun., 2013, DOI: 10.1039/C3CC46498A.
Volume 46 | Number 32 | 2010
ccess
This is an Accepted Manuscript, which has been through the RSC Publishing peer review process and has been accepted for publication. Chemical Communications www.rsc.org/chemcomm
Volume 46 | Number 32 | 28 August 2010 | Pages 5813–5976
ChemComm
the chemical
to therapeutic
etic and
Accepted Manuscripts are published online shortly after acceptance, which is prior to technical editing, formatting and proof reading. This free service from RSC Publishing allows authors to make their results available to the community, in citable form, before publication of the edited article. This Accepted Manuscript will be replaced by the edited and formatted Advance Article as soon as this is available. To cite this manuscript please use its permanent Digital Object Identifier (DOI®), which is identical for all formats of publication.
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More information about Accepted Manuscripts can be found in the Information for Authors.
inical systems.
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Pages 5813–5976
org/journals
ISSN 1359-7345
COMMUNICATION J. Fraser Stoddart et al. Directed self-assembly of a ring-in-ring complex
FEATURE ARTICLE Wenbin Lin et al. Hybrid nanomaterials for biomedical applications
1359-7345(2010)46:32;1-H
Please note that technical editing may introduce minor changes to the text and/or graphics contained in the manuscript submitted by the author(s) which may alter content, and that the standard Terms & Conditions and the ethical guidelines that apply to the journal are still applicable. In no event shall the RSC be held responsible for any errors or omissions in these Accepted Manuscript manuscripts or any consequences arising from the use of any information contained in them.
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NIR-fluorescent coumarin-fused BODIPY dyes with large Stokes shifts Andrei Y. Bochkov,*a‡ Igor O. Akchurin,a‡ Oleg A. Dyachenkob and Valery F. Travena
Published on 21 October 2013. Downloaded by University of Virginia on 24/10/2013 15:31:43.
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A series of novel non-symmetrical coumarin-fused BODIPY dyes were synthesised. Their absorption and emission properties are strongly influenced by substitution in coumarin moiety. Diethylamino-substituted dyes showed near-IR emission with large Stokes shifts (up to 144 nm) and good fluorescence quantum yields. 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives are fluorescent dyes having many advantages over other classes of dyes, namely high extinction and fluorescence quantum yields which are usually weakly affected by solvent polarity, sharp absorption and emission bands, excellent photo- and chemical stability. 1 Because of their outstanding properties BODIPYs are considered as dyes of choice for many applications, such as fluorescent sensors, 2 fluorescent labeling of biomolecules and fluorescent imaging of cells,3 photodynamic therapy, 4 laser dyes,5 photovoltaics,6 lightemitting devices7 etc. For some applications, in particular biochemical, large Stokes shifts and near-IR fluorescence are highly desirable, but classical BODIPYs absorb light in the range of 500–600 nm and have rather small Stokes shifts (15– 30 nm). To address these issues a number of approaches have been reported. Extension of the π-conjugation by fusion of various aryl cycles to BODIPY core is being extensively developed in recent years. A variety of BODIPY dyes have been prepared starting from fused pyrroles, such as benzofuro[3,2-b]pyrrole and thianaphtheno[3,2-b]pyrrole,8 furo[3,2-b]pyrrole,9 thieno[3,2-b]pyrrole,10 1,4,5,5atetrahydrochromeno[2,3-g]indole, 11 isoindole,12 2Hdibenzo[e,g]isoindole,13 fluoranthro[8,9-f]isoindole,14 indole,15 and benzo[1,2-b:5,4-b']dipyrrole. 15b Alternatively aryl annulations were performed by oxidative cyclodehydrogenation of BODIPYs having electron-rich aryl substituents to give anthracene-, perylene- or phenanthrenefused systems.16 We suggested that annulation of coumarin unit to BODIPY core would shift emission to the red region and Stokes shifts of resulting dyes are likely to be higher compared to typical non-annulated BODIPYs. Coumarin derivatives represent a unique class of fluorescent dyes, exhibiting high fluorescence quantum yields and large Stokes shifts.17 An example of successful coumarin-fusion approach was published recently when this manuscript was in preparation. Wang et al. reported synthesis of dyes having coumarin- and rhodamine-fused conjugated skeleton, which exhibited emission in the deep red This journal is © The Royal Society of Chemistry [year]
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Scheme 1 Synthetic route to coumarin-fused BODIPY dyes. Reagents and conditions: (a) DMF, POCl3, 60–84 %; (b) Ph3P=CHBz, DCM, RT, 24 h, 55–93 %; (c) NaN3, acetone, 85–88 %; (d) toluene, reflux, 1 h, 67– 96 %; (e) i: POCl3, DCM, RT; ii: TEA; iii: BF3×OEt2, 30–58 %.
region with large Stokes shift.18 Herein we report synthesis and spectral study of nonsymmetrical BODIPY dyes 1 having 7-substituted chromeno[4,3-b]pyrrol-4-one and alkylpyrrole as pyrromethene-forming units. Compounds 1c-d bearing diethylamino donor in coumarin moiety exhibit NIR emission and large Stokes shifts. Synthetic route to coumarin-fused BODIPYs is shown in Scheme 1. The key BODIPY precursors 2benzoylchromeno[4,3-b]pyrrol-4-ones 6 were prepared using novel approach developed by us. Preparation of some 3acylchromeno[4,3-b]pyrrol-4-ones by cyclocondensation of chloroaldehyde 3a with α-aminoketones was reported in literature, but presence of two reactive functions (chloro- and formyl-) caused side reactions and considerable by-products formation.19 In our approach these functions are involved in step by step transformations in mild conditions. Firstly, 4hydroxycoumarins were subjected to Vilsmeier reaction to give corresponding 4-chloro-3-formylcoumarins 3. The acylvinyl moiety was constructed using Wittig reaction and then chlorine was substituted by azide-ion. The resulting 4azido-3-(2-benzoylvinyl)coumarins 5 were thermally cyclized to fused pyrroles 6. The above approach affords 2-benzoyl[journal], [year], [vol], 00–00 | 1
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chromeno[4,3-b]pyrrol-4-ones 6a-c in 4 steps starting from 4hydroxycoumarins in high overall yields and may be expanded for preparation of 2-acyl-, 2-carbonyl-, 2-alkyl- and 2-arylchromeno[4,3-b]pyrrol-4-ones as corresponding Wittig reagents are easily available. Finally, desired BODIPY dyes 1a-d were prepared following conventional two-step protocol without isolation of dipyrromethene intermediate. Reactivity of 6a-c turned to be low and formation of dipyrromethene required several days (up to one week) albeit yields of 1a-d were good. The detailed synthetic procedures and compounds characterisation data are given in the ESI.† Single-crystal X-ray diffraction analysis of compound 1c (Fig. 1) revealed high planarity of pentacyclic conjugated skeleton and almost orthogonally rotated phenyl ring (dihedral angle 102.1°). Shortened distances between fluorine atoms and hydrogen atom attached to position 5 (C3) of coumarin fragment seem to be concerned with intramolecular hydrogen bonding. In benzene ring with attached diethylaminosubstituent bonds C2–C3 and C18–C19 are shorter compared with remaining four bonds, and C1–N1 bond is also more akin to a double bond that indicates significant contribution of para-quinoidal resonance state in 7-dialkylaminocoumarins.20 UV-vis absorption and emission properties of coumarinfused BODIPYs were studied in solvents of different polarity (Table 1). Dye 1a with non-substituted coumarin moiety shows two clearly separated absorption bands (Fig. 1): in 300 nm region and narrow band with shoulder and maximum at 516 nm (DCM, ε 3.6×104 M-1×cm-1). Intense emission band maximum is located at 546 nm (φ F 0.66). Stokes shift of 1a in DCM is 1065 cm-1. In higher polarity solvents (MeOH, DMF) absorption bands are slightly blue-shifted, while emisson maximum in MeOH also shifts to blue region for 4 nm and emission maximum in DMF shifts to red region for 5 nm. Absorption and emission properties of 1a are similar to those of 1,3,5,7-tetramethyl-2,6-diethyl-8-phenyl-BODIPY.21 Thus fusion of non-substituted coumarin to BODIPY doesn’t afford longer wavelength absorbing dye. Hydroxy-substituted dye 1b shows red-shifted absorption and emission maxima and higher extinction as compared to 1a. It is noteworthy that fluorescence quantum yield of 1b in polar protic solvent (MeOH) is relatively high (φ F 0.65) while being much lower in polar aprotic solvent (DMF) (φF 0.15).
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Fig. 2 UV-vis absorption (solid) and fluorescence (dashed) spectra of 1a-d in DCM. Table 1 Photophysical properties of coumarin-fused BODIPYs 1. solvent λabs (nm) ε (M-1×cm-1) λem (nm) ∆ν (cm-1) DCM 516 36000 546 1065 MeOH 504 –b 542 1391 DMF 510 29600 551 1459 PhMe 548 52200 578 947 1b DCM 530 46200 567 1231 MeOH 530 49400 579 1597 DMF 538 66800 595 1781 CyH 620 68500 643 577 1c PhMe 632 62700 672 942 DCM 602 59400 697 2264 MeOH 590 46000 720 3060 DMF 606 43900 748 3133 b 642 553 CyH 620 – 1d DCM 606 59100 706 2337 MeOH 594 –b 724 3023 DMF 608 41600 752 3150 8-PhBDPc DCM 524 NA 544 702 compd 1a
φFa 0.66 –b 0.18 0.71 0.64 0.65 0.15 0.86 0.62 0.41 0.06 0.04 –b 0.31 –b 0.03 0.85
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Quantum yields determined with references Rhodamine 6G (1a-b) and Cresyl Violet (1c-d). b Not measured due to very low solubility. c 2,6diethyl-1,3,5,7-tetramethyl-8-phenyl-BODIPY, data from ref. 21.
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Diethylamino-substituted dye 1c expectedly exhibits dramatic bathochromic shift of absorption and emission bands. Since excited states of 7-aminocoumarins have strong intramolecular charge tranfer (ICT) character 20 their absorption and fluorescent charachteristics are strongly dependent on solvent polarity. Absorption of compound 1c shows negative solvatochromism. With increasing solvent polarity its absorption maximum wavelength shifts from 632 nm (toluene) to 590 nm (MeOH). Emission maximum gradually shifts to infra-red region from 643 nm (cyclohexane) to 748 nm (DMF) when solvent polarity increases and fluorescence quantum yields decrease simultaneously. In highly polar solvents (MeOH and DMF) fluorescence is quenched in significant extent (φF 0.06 and 0.04 respectively). One of possible explanations for this may be formation of twisted ICT (TICT) excited state with full charge separation in polar media (positively charged dialkylamino group is rotated orthogonally to the plane of the molecule). In 7-dialkylaminocoumarins TICT excited states are considered to be non-emissive but having non-radiative decay pathway. 22 This journal is © The Royal Society of Chemistry [year]
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Fig. 1 Molecular structure of 1c in the crystal. Selected bond lengths (Å): C1–N1, 1.372; C2–C3, 1.376; C18–C19, 1.377; С3–F1, 3.279(3); Н3–F1, 2.54; С3–F2, 3.019(3); Н3–F2, 2.32.
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Compound 1d was synthesized to examine influence of substitution in alkylpyrrole unit on spectral properties of coumarin-fused BODIPY. Absorption and fluorescence maxima of 1d have slightly longer wavelengths as compared to 1c. This was surprising, because from previously reported data is clear that replacement of 2-ethyl-substituent with hydrogen for symmetrical 23 or non-symmetrical12f BODIPYs causes blue shift of absorption and emission bands of about 20–25 nm. Stokes shifts of BODIPYs 1c-d in polar solvents (MeOH, DMF) are among the highest ever reported for BODIPY derivatives. Most of deep red or near-IR emissive (λem > 650 nm) BODIPYs with large Stokes shifts ( ∆ν > 1500 cm1 15,16a,16b,24 ) suffer from low emission efficiency (φF < 0.1). 3,5-Dioligothienyl-BODIPYs recently reported by Ziessel’s group exhibit NIR-emission with rather large Stokes shifts and moderate quantum yields.25 Coumarin-fused BODIPYs 1c-d showed good balance between Stokes shifts and quantum yields in dichloromethane solutions ( ∆ν 2264–2337 cm-1, φ F 0.31–0.41), which is exceptional for near-IR fluorescent BODIPYs. In summary, a synthetic route to non-symmetrical BODIPYs fused with coumarin was developed. A series of novel dyes with varied substitution both in chromenopyrrole and alkylpyrrole units were prepared and their spectral properties were studied. Coumarin-fused BODIPYs having diethylamino-substitution in coumarin skeleton showed an exceptional photophysical properties combination in moderately polar solvent dichloromethane: intense absorption (5.9×104 M-1×cm-1), near-IR emission (λem 697–706 nm), large Stokes shifts (2264–2337 cm-1, 95–100 nm) and rather high quantum yields (0.31–0.41). In highly polar solvents emission is shifted up to 750 nm affording Stokes shifts as high as 144 nm (3150 cm-1). We consider coumarin-fused BODIPY to be a useful scaffold for design of new efficient NIR-emitting dyes with large Stokes shifts for various applications.
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a Department of Organic Chemistry, Mendeleev University of Chemical Technology, 125047, Miusskaya square 9, Moscow, Russian Federation. E-mail: [email protected]; Fax: +7 495 609 2964. b Institute of Problems of Chemical Physics, 142432, Academician Semenov avenue 1, Chernogolovka, Moscow Region, Russian Federation. † Electronic Supplementary Information (ESI) available: Experimental procedures, charachterization data, UV-vis and fluorescence spectra and X-ray crystallographic data for 1c (CCDC 956947). See DOI: 10.1039/b000000x ‡ These authors contributed equally to this work. 1 (a) A. Loudet and K. Burgess, Chem. Rev., 2007, 107, 4891; (b) G. Ulrich, R. Ziessel and A. Harriman, Angew. Chem. Int. Ed., 2008, 47, 1184. 2 V. Leen and W. Dehaen, Chem. Soc. Rev., 2012, 41, 1130. 3 (a) Y. Gabe, Y. Urano, K. Kikuchi, H. Kojima and T. Nagano, J. Am. Chem. Soc., 2004, 126, 3357; (b) Y. Urano, D. Asanuma, Y. Hama, Y. Koyama, T. Barrett, M. Kamiya, T. Nagano, T. Watanabe, A. Hasegawa, P. L. Choyke and H. Kobayashi, Nature Medicine, 2009, 15, 104; (c) J. Han, A. Loudet, R. Barhoumi, R. C. Burghardt and K. Burgess, J. Am. Chem. Soc., 2009, 131, 1642; (d) D. W. Domaille, L. Zeng and C. J. Chang, J. Am. Chem. Soc., 2010, 132, 1194; (e) A. Matsui, K. Umezawa, Y. Shindo, T. Fujii, D. Citterio, K. Oka and K. Suzuki, Chem. Commun., 2011, 47, 10407.
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