Review on synthetic strategies of red emitting coumarins
Chapter 1 1.1 Introduction
Fluorescence has found applications in well-known technologies like compact fluorescent
lamps and light emitting diodes (LED) 1. It is not only popular in day-to-day applications
but also used in the areas like array detectors2 and HPLC analysis3–5. It has become a
versatile tool for various applications in biology like fluorescence microscopy6,
fluorescence lifetime imaging microscopy7, cellular imaging 8, protein labelling9 etc. Use
of the fluorescent molecules for various diagnostic techniques minimizes the use of
radioactive materials
10
. The radioactive materials poses a risk of cancer11 and gene
mutation12. They are not readily available as their production and storage is expensive.
The radioactive materials are usually metals and have toxic effects on living tissues.
Biological applications of fluorescent molecules have increased in recent years due to
their sensitivity and selectivity 13. The fluorophores are the molecules consisting of donor
and acceptor groups separated by π-bonds and can emit light on irradiation. Modification
of various groups on the organic fluorophore gives a wide range of fluorescent materials
to be used in these applications14.There is wider range of wavelengths necessary for the
various applications of fluorescence such as blue colored fluorescent molecules are used
as optical brighteners15, Green Fluorescent Protein (GFP) has been used as marker for cell
dynamics9,16, and various coumarin and rhodamine dyes of different wavelengths are
being used as laser dyes. Here we have focused only on the red emitting (600-800nm)
molecules which are of are of interest in many applications such as OLED17, protein
tracking18, multicolor imaging19, far-field optical nanoscopy20,21. The need of the red
fluorescent materials is not only to achieve diversity in the emission wavelengths but has
other aspects too in various fields.
In OLED (Organic Light Emitting Diode) technology there is need of the
electroluminescent materials with the colors RGB (Red, Green, Blue)22. Research of more
than a decade has developed the luminescent materials which emit in green23,24 and
blue25–28. Though there are materials29,30 for the red luminescence, the property is
achieved by doping the red dye into suitable host material. The mixture of all the three
(Red, Blue and Green) lights can provide an array of colours to the display. The most
advanced displays with less power consumption run on OLED technology. The enlarged
view of the typical OLED display with RGB components is shown in figure Figure 1.1.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 1
Review on synthetic strategies of red emitting coumarins
Chapter 1 Figure 1.1 Typical OLED display with RGB component
The required red dyes need to give a bright luminescent materials and high quantum
efficiencies. For a saturated red colored emission the emission band should have
maximum emission beyond 600 nm, which is not the case for the present dyes31 which
possess the emission band below 600 nm Figure 1.2. As a result the dyes are not able to
provide a saturated red colored emission. So there is a need of red luminescent materials,
which possess maximum emission band beyond 600nm and can match the brightness
shown by green and blue materials Figure 1.2.
Figure 1.2 Color saturation of red color
Typical red dyes involves the higher charge separation between donor and acceptor
groups and possess higher dipole moments, due to which they lack in the air stability and
also lead to higher degree of self-quenching30.
In biological applications the red emitting dyes stands apart in usefulness. The signal
from the probe can be detected with more selectivity and sensitivity when the background
noise is minimum. The biomolecule tends to show an intrinsic fluorescence from various
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 2
Review on synthetic strategies of red emitting coumarins
Chapter 1 residues and molecules such as tryptophan residue. Emission of fluorescent marker in red
region avoid the interference from auto-fluorescence of the biomolecule which falls in
yellow-green region32–34. The probes which emit in blue-green region (400-600nm) needs
an excitation wavelength falling in the ultra-violet region. The higher energy radiation
(usually in UV region) is known to be detrimental to the living cells35. Whereas the use of
far-red emitting probes need the light in visible region which is less degenerative in
nature for living cells. The NIR wavelengths are known to have a higher penetration
power in living tissue than the shorter wavelength radiation. The region of 620nm1300nm is also known as biological window Figure 1.3 , which exhibit highest
penetration in the tissue36–39.
Figure 1.3 Effective penetration against wavelength in biological tissues.
The optics used for the red region is simpler as the scattering effect for the red region is
minimal. In this way the red emitting probes provide the bio-analyst with a less noisy,
higher penetrating and simpler technique to study the various biological phenomena40.
For all these purposes red dyes available are like rhodamine21,41,42, cyanine43–45,
fluorescein 46,47 and oxazine 48.
The coumarin molecules are not much studied for their ability to cater as red emitting
molecules for the various applications. Coumarin molecules are known to have a good
quantum yield
49–52
, high phostability51,53,54 which is necessary for photonic applications.
The most of the coumarins are known to be available with blue-green fluorescence55–59.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 3
Review on synthetic strategies of red emitting coumarins
Chapter 1 1.2 Strategies to red coumarins
There have been a few attempts in the literature to synthesize the red emitting coumarins
(> 600nm) with different strategies. The literature reports various ways of sustitutions and
donor-acceptor arrangements for coumarins to achieve red shifted emissions.
1.2.1 Rigidisation of acceptor
The first red emitting dyestuff with red emission containing modified coumarin moiety is
reported by Mach Wolfgang et al
in 1974
60
. They have rigidised the electron
withdrawing benzimidazole ring by cyclizing iminocoumarin with malononitrile at high
temperature Figure 1.4.
Figure 1.4 Rigidisation of acceptor
This rigidisation increased the extent of charge transfer from donor (here –NEt2) to
acceptor (benzimidazole) by inducing planarity to the structure. Also the –CN group acts
as an acceptor and increases the acceptor capacity of newly formed six membered ring.
1.2.2 Rigidisation of donor
The way rigidisation of acceptor plays an important role in red shift of coumarin,
rigidisation of donor also contributes. In the example given in
Figure 1.5 shows a red shift
of 14nm in coumarin molecule having all other structural specification the same. Due to
rigidised donor the extent of charge transfer is higher as compared to the free-to-rotate
donor group.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 4
Review on synthetic strategies of red emitting coumarins
Chapter 1 Figure 1.5 Rigidisation of donor.
1.2.3 Cyano group at 4-position
Another route followed to synthesize a red emitting dye with coumarin moiety was to
introduce –CN group at 4-position. This was achieved by oxidative cyanation with
sodium cyanide and molecular bromine was used as oxidizing agent Figure 1.6. Prior to
oxidative cyanation the compound showed yellow color, and turned red colored
afterwards n61.
Figure 1.6 Oxidative cyanation at 4-Position
The introduction of –CN group at 4-position has induced a shift of 67nm in absorption
spectrum. The concept is proved with the help of other coumarin dyes, which on
introduction of –CN group showed a red shift which also can be sensed visually Figure
1.7.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 5
Review on synthetic strategies of red emitting coumarins
Chapter 1 Figure 1.7 Effect of cyanation at 4-position
It is proved with examples that in each case the introduction of –CN group is responsible
for a red shift in the coumarin molecules. As the donor not being a strong one the
molecule fell in the yellow region only despite having cyano group at 4-position.
1.2.4 Length of conjugation
This is well reported in the literature that the extension of conjugation leads to longer
wavelength absorption and emission of coumarin molecules62,63.
Figure 1.8 Extension of conjugation
Here at 3-position an electron withdrawing group has been introduced and is separated by
a π-bridge. This leads to a longer wavelength emission due to effective conjugation and
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 6
Review on synthetic strategies of red emitting coumarins
Chapter 1 lowering of band gap as a result of extended conjugation. It is also observed that the
nature of electron withdrawing group decides the extent of red shift in this type of
molecules62.
1.2.5 Mixed strategy
A series of coumarins have been synthesized64 which featured the structural modifications
known in previous syntheses60–63. See Figure 1.9. The cyclization with malononitrile has
rigidised the acceptor and further introduction of an electron withdrawing group shifted
the absorption to the red region.
Figure 1.9 Red emitting coumarin with various structural features.
The –CN groups also adds to the better electron withdrawing effect and contributes to the
red shift of the molecules. The sulphonamide phenyl ring bearing a carboxylic acid acts
as an anchoring group for the conjugation purpose. The variation in electron donating
groups at 7-position does not alter the photophysical properties to a great extent (either Ethyl or –Butyl).
1.3 Conclusion
From the examples above we can broadly say that following structural features lead
coumarin structures to the red emission.
1) Donor at 7- position.
2) Acceptor at 3-position.
3) Acceptor at 4-position (e.g. -CN)
4) Rigidisation of the donors and acceptors
5) Length of conjugation.
There is good amount of work has been done on estimating the photophysical properties
of coumarin dyes. Though this aspect further needs to be explored for better utility of
these kind of molecules.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 7
Review on synthetic strategies of red emitting coumarins
Chapter 1 1.4 References
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
Guo, C.; Huang, D.; Su, Q. Mater. Sci. Eng. B 2006, 130, 189–193.
Hart, S.; Hall, G.; Kenny, J. Anal. Bioanal. Chem. 2002, 372, 205–215.
Kono, Y.; Iizuka, H.; Isokawa, M.; Tsunoda, M.; Ichiba, H.; Sadamoto, K.;
Fukushima, T. Biomed. Chromatogr. 2014.
Guo, X.-F.; Li, Y.; Wang, H.; Zhang, H.-S. Chromatographia 2014.
Shahbazi, S.; Peer, C. J.; Polizzotto, M. N.; Uldrick, T. S.; Roth, J.; Wyvill, K. M.;
Aleman, K.; Zeldis, J. B.; Yarchoan, R.; Figg, W. D. J. Pharm. Biomed. Anal.
2014, 92C, 63–68.
Johnson, T.; Sikora, A.; Zielke, R.; Sandkvist, M. In Bacterial Cell Surfaces SE 10; Delcour, A. H., Ed.; Methods in Molecular Biology; Humana Press, 2013; Vol.
966, pp. 157–172.
Hum, J. M.; Siegel, A. P.; Pavalko, F. M.; Day, R. N. Int. J. Mol. Sci. 2012, 13,
14385–400.
Liu, Q.; Guo, B.; Rao, Z.; Zhang, B.; Gong, J. R. Nano Lett. 2013, 13, 2436–41.
Jung, D.; Min, K.; Jung, J.; Jang, W.; Kwon, Y. Mol. Biosyst. 2013, 9, 862–72.
Pickering, A. M.; Davies, K. J. A. Free Radic. Biol. Med. 2012, 52, 239–46.
Linet, M. S.; Slovis, T. L.; Miller, D. L.; Kleinerman, R.; Lee, C.; Rajaraman, P.;
Berrington de Gonzalez, A. CA. Cancer J. Clin. 2012.
Thacker, J. Mutat. Res. Mol. Mech. Mutagen. 1986, 160, 267–275.
Wang, X.; Cui, L.; Zhou, N.; Zhu, W.; Wang, R.; Qian, X.; Xu, Y. Chem. Sci.
2013, 4, 2936.
Yang, L.; Ye, J.; Gao, Y.; Deng, D.; Gong, W.; Lin, Y.; Ning, G. Tetrahedron Lett.
2013, 54, 2967–2971.
Ullmann’s Encyclopedia of Industrial Chemistry; Wiley-VCH Verlag GmbH &
Co. KGaA: Weinheim, Germany, 2000.
Gerdes, H.-H.; Kaether, C. FEBS Lett. 1996, 389, 44–47.
Chang, Y. J.; Chow, T. J. J. Mater. Chem. 2011, 21, 3091–3099.
Kotani, M.; Kikuta, J.; Klauschen, F.; Chino, T.; Kobayashi, Y.; Yasuda, H.;
Tamai, K.; Miyawaki, A.; Kanagawa, O.; Tomura, M.; Ishii, M. J. Immunol. 2013,
190, 605–612.
Tynan, C. J.; Clarke, D. T.; Coles, B. C.; Rolfe, D. J.; Martin-Fernandez, M. L.;
Webb, S. E. D. PLoS One 2012, 7, 362–365.
Kolmakov, K.; Belov, V. N.; Wurm, C. A.; Harke, B.; Leutenegger, M.; Eggeling,
C.; Hell, S. W. European J. Org. Chem. 2010, 3593–3610.
Mitronova, G. Y.; Belov, V. N.; Bossi, M. L.; Wurm, C. A.; Meyer, L.; Medda, R.;
Moneron, G.; Bretschneider, S.; Eggeling, C.; Jakobs, S.; Hell, S. W. Chemistry
2010, 16, 4477–4488.
Kanno, H.; Hamada, Y.; Matsusue, N.; Takahashi, H.; Nishikawa, R.; Mameno, K.
In Optical Science and Technology, SPIE’s 48th Annual Meeting; Kafafi, Z. H.;
Lane, P. A., Eds.; International Society for Optics and Photonics, 2004; pp. 31–39.
Ni, Y. R.; Su, H. Q.; Huang, W.; Zhao, J. F.; Qian, Y.; Xie, L. H.; Xie, G. H.;
Zhao, Y. Appl. Mech. Mater. 2013, 331, 503–507.
Kim, S.-J.; Zhang, Y.; Zuniga, C.; Barlow, S.; Marder, S. R.; Kippelen, B. Org.
Electron. 2011, 12, 492–496.
Moon, B.-J.; Yook, K. S.; Lee, J. Y.; Shin, S.; Hwang, S.-H. J. Lumin. 2012, 132,
2557–2560.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 8
Review on synthetic strategies of red emitting coumarins
Chapter 1 (26)
(27)
(28)
(29)
(30)
(31)
(32)
(33)
(34)
(35)
(36)
(37)
(38)
(39)
(40)
(41)
(42)
(43)
(44)
(45)
(46)
(47)
(48)
(49)
(50)
(51)
Kessler, F.; Watanabe, Y.; Sasabe, H.; Katagiri, H.; Nazeeruddin, M. K.; Grätzel,
M.; Kido, J. J. Mater. Chem. C 2013, 1, 1070.
Sun, Q.; Li, D.; Dong, G.; Jin, X.; Duan, L.; Wang, L.; Qiu, Y. Sensors Actuators
B Chem. 2013, 188, 879–885.
Giovanella, U.; Botta, C.; Galeotti, F.; Vercelli, B.; Battiato, S.; Pasini, M. J.
Mater. Chem. C 2013, 1, 5322.
Yao, Y.-S.; Zhou, Q.-X.; Wang, X.-S.; Wang, Y.; Zhang, B.-W. Adv. Funct.
Mater. 2007, 17, 93–100.
Chen, C.-T. Chem. Mater. 2004, 16, 4389–4400.
Zhang, X. H.; Chen, B. J.; Lin, X. Q.; Wong, O. Y.; Lee, C. S.; Kwong, H. L.; Lee,
S. T.; Wu, S. K. Chem. Mater. 2001, 13, 1565–1569.
Rich, R. M.; Stankowska, D. L.; Maliwal, B. P.; Sørensen, T. J.; Laursen, B. W.;
Krishnamoorthy, R. R.; Gryczynski, Z.; Borejdo, J.; Gryczynski, I.; Fudala, R.
Anal. Bioanal. Chem. 2013, 405, 2065–2075.
Pang, Z.; Barash, E.; Santamaria-Pang, A.; Sevinsky, C.; Li, Q.; Ginty, F. Microsc.
Res. Tech. 2013, 76, 1007–15.
Stelzle, F.; Knipfer, C.; Adler, W.; Rohde, M.; Oetter, N.; Nkenke, E.; Schmidt,
M.; Tangermann-Gerk, K. Sensors (Basel). 2013, 13, 13717–31.
Matsumura, Y.; Ananthaswamy, H. N. Toxicol. Appl. Pharmacol. 2004, 195, 298–
308.
Behnke, T.; Mathejczyk, J. E.; Brehm, R.; Würth, C.; Ramos Gomes, F.; Dullin,
C.; Napp, J.; Alves, F.; Resch-Genger, U. Biomaterials 2013, 34, 160–170.
Iwano, S.; Obata, R.; Miura, C.; Kiyama, M.; Hama, K.; Nakamura, M.; Amano,
Y.; Kojima, S.; Hirano, T.; Maki, S.; Niwa, H. Tetrahedron 2013, 69, 3847–3856.
Hong, G.; Lee, J. C.; Robinson, J. T.; Raaz, U.; Xie, L.; Huang, N. F.; Cooke, J. P.;
Dai, H. Nat. Med. 2012, 18, 1841–1846.
Pham, W.; Cassell, L.; Gillman, A.; Koktysh, D.; Gore, J. C. Chem. Commun.
(Camb). 2008, 1895–7.
Raghavachari, R. Near-Infrared Applications in Biotechnology; Raghavachari, R.,
Ed.; CRC Press: New York, 2000.
Boyarskiy, V. P.; Belov, V. N.; Medda, R.; Hein, B.; Bossi, M.; Hell, S. W.
Chemistry 2008, 14, 1784–1792.
Kolmakov, K.; Belov, V. N.; Bierwagen, J.; Ringemann, C.; Müller, V.; Eggeling,
C.; Hell, S. W. Chemistry 2010, 16, 158–166.
Mujumdar, R. B.; Ernst, L. A.; Mujumdar, S. R.; Lewis, C. J.; Waggoner, A. S.
Bioconjug. Chem. 1993, 4, 105–111.
Fei, X.; Gu, Y.; Li, C.; Liu, Y.; Yu, L. J. Fluoresc. 2013, 23, 221–226.
Bouteiller, C.; Clavé, G.; Bernardin, A.; Chipon, B.; Massonneau, M.; Renard, P.Y.; Romieu, A. Bioconjug. Chem. 2007, 18, 1303–1317.
Lavis, L. D.; Raines, R. T. ACS Chem. Biol. 2008, 3, 142–55.
Romieu, A.; Tavernier-Lohr, D.; Pellet-Rostaing, S.; Lemaire, M.; Renard, P.-Y.
Tetrahedron Lett. 2010, 51, 3304–3308.
Nieckarz, R. J.; Oomens, J.; Berden, G.; Sagulenko, P.; Zenobi, R. Phys. Chem.
Chem. Phys. 2013, 15, 5049–56.
Cigáň, M.; Donovalová, J.; Szöcs, V.; Gašpar, J.; Jakusová, K.; Gáplovský, A. J.
Phys. Chem. A 2013, 117, 4870–4883.
Krzeszewski, M.; Vakuliuk, O.; Gryko, D. T. European J. Org. Chem. 2013, 2013,
5631–5644.
Nizamov, S.; Willig, K. I.; Sednev, M. V; Belov, V. N.; Hell, S. W. Chemistry
2012, 18, 16339–48.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 9
Review on synthetic strategies of red emitting coumarins
Chapter 1 (52)
(53)
(54)
(55)
(56)
(57)
(58)
(59)
(60)
(61)
(62)
(63)
(64)
Li, J.; Li, X.; Wang, S. J. Mol. Struct. 2012, 1011, 19–24.
Azzouz, I. M.; Salah, A. Appl. Phys. B 2012, 108, 469–474.
Chen, J.; Liu, W.; Zhou, B.; Niu, G.; Zhang, H.; Wu, J.; Wang, Y.; Ju, W.; Wang,
P. J. Org. Chem. 2013, 78, 6121–6130.
Ye, D.; Wang, L.; Li, H.; Zhou, J.; Cao, D. Sensors Actuators B Chem. 2013, 181,
234–243.
Yu, T.; Zhang, C.; Zhao, Y.; Chai, H.; Fan, D.; Ma, Y.; Yao, S.; Li, W.
Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 2013, 108, 274–279.
Stopiglia, C. D. O.; Carissimi, M.; Daboit, T. C.; Stefani, V.; Corbellini, V. A.;
Scroferneker, M. L. Rev. Inst. Med. Trop. Sao Paulo 55, 353–6.
Ghouili, A.; Dusek, M.; Petricek, V.; Ayed, T. Ben; Hassen, R. Ben J. Phys. Chem.
Solids 2013.
Sun, Y.-F.; Wang, H.-P.; Chen, Z.-Y.; Duan, W.-Z. J. Fluoresc. 2013, 23, 123–30.
Wolfgang, M.; Dietmar, A.; Scheuermann, H. Farbstoffe der Benzopyranreihe.
DE2253538, 1974.
Moeckli, P. Dye. Pigment. 1980, 1, 3–15.
Griffiths, J.; Millar, V.; Bahra, G. Dye. Pigment. 1995, 28, 327–339.
Raju, B. B.; Varadarajan, T. S. J. Photochem. Photobiol. A Chem. 1995, 85, 263–
267.
Huang, S.-T.; Jian, J.-L.; Peng, H.-Z.; Wang, K.-L.; Lin, C.-M.; Huang, C.-H.;
Yang, T. C.-K. Dye. Pigment. 2010, 86, 6–14.
Red emitting coumarin, phenazine colorants: Synthesis, spectroscopic and DFT studies 10