- Email: [email protected]
Synthesis and physico-chemical properties of cyclotriphosphazene-BODIPY conjugates
Accepted Manuscript Synthesis and physico-chemical properties of cyclotriphosphazene-BODIPY conjugates Seda Çetindere, Süreyya Oğuz Tümay, Adem Kılıç, Mahmut Durmuş, Serkan Yeşilot PII:
S0143-7208(16)30820-8
DOI:
10.1016/j.dyepig.2016.12.035
Reference:
DYPI 5660
To appear in:
Dyes and Pigments
Received Date: 25 September 2016 Revised Date:
10 December 2016
Accepted Date: 15 December 2016
Please cite this article as: Çetindere S, Tümay SO, Kılıç A, Durmuş M, Yeşilot S, Synthesis and physicochemical properties of cyclotriphosphazene-BODIPY conjugates, Dyes and Pigments (2017), doi: 10.1016/j.dyepig.2016.12.035. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Synthesis and physico-chemical properties of cyclotriphosphazene-BODIPY conjugates Seda Çetindere, Süreyya Oğuz Tümay, Adem Kılıç, Mahmut Durmuş, Serkan Yeşilot*
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Contribution from:
Department of Chemistry, Gebze Technical University, Gebze, Kocaeli, Turkey
Author for correspondence:
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*
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Professor Serkan YEŞİLOT, Department of Chemistry, Gebze Technical University, P.O.Box: 141, Gebze 41400, Kocaeli, Turkey Tel:
00 90 262 6053014
Fax:
00 90 262 6053005
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e-mail : [email protected]
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Abstract
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The novel cyclotriphosphazene compounds bearing mono- and distyryl BODIPY substituents were synthesized and characterized by the standard spectroscopic techniques such as 1H, 13C and 31P NMR, mass spectrometry (MALDITOF) and FT-IR spectroscopy and elemental analysis as well. The photophysical properties of these novel cyclotriphosphazene compounds
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were investigated in tetrahydrofuran (THF) solutions. The singlet oxygen generation ability of these compounds was also investigated depends on the addition of an acid solution. It was found that the singlet oxygen producing ability of the dyes was dramatically increased
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under the acidic conditions when compared to the initial state, and these results indicate that
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these dyes can be potential singlet oxygen photosensitizers.
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Keywords: Cyclotriphosphazene, BODIPY, Singlet Oxygen, Photophysical, Photochemical
ACCEPTED MANUSCRIPT 1. Introduction Photosensitized generation of singlet oxygen (1O2) is a well-studied phenomenon, which has found various applications from synthetic organic chemistry such as ene reactions, hetero Diels Alder reaction, [2+2] cycloaddition reactions [1-2] and photodynamic therapy (PDT) [3-
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4]. The generation of singlet oxygen in solution requires a photosensitizer (PS) which is converted to the triplet excited state (intersystemcrossing, ISC) upon irradiation. Many dyes obtained from natural or synthetic sources with a high intersystem crossing (ISC) have been
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used for reactions of singlet oxygen and PDT. Nowadays boradiazaindacene (BODIPY) dyes show superior sensitizer properties due to their long wavelength excitability, good solubility
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and non-toxicity behaviors and high singlet oxygen generation capacity [5, 6]. The heavy atom effect has been a useful chemical approach to improve ISC in several molecules including BODIPY chromophores [7-8]. But intersystem crossing (ISC) without heavy atoms can only be accomplished by a limited number of BODIPY photosensitizers; hence,
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substantial effort is dedicated to the search of novel compounds and strategies [9-14]. However, the photoinduced electron transfer (PET) is one of the most popular mechanisms to switch the singlet excited state of organic chromophores [15] such as BODIPY [16].
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Concerning the controlling of the triplet excited states, O’shea and his co-workers previously studied the acid-activated PDT effect of the azaBodipy derivatives under neutral and acidic
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conditions [17]. Protonation of the amino moiety on BODIPY compounds may inhibit the PET, as a result the 1O2 photosensitizing ability may be enhanced. This molecular designing rational is based on the study of the PET modulated fluorescence [15]. Cyclotriphosphazenes are an interesting class of materials with a planar nondelocalized cyclic ring consisting of alternating N and P atoms. The inorganic phosphazenes have been well studied by several groups due to their diverse properties including excellent hydrolytic stability, thermal stability, flame retardant properties and
ACCEPTED MANUSCRIPT liquid crystalline behavior [18-23]. The cyclotriphosphazene core (CP) serves many advantageous. For example the chemistry to prepare functionalized CP cores is very straightforward, the functionalized CP cores are very stable and do not breakdown even under very aggressive chemical conditions and the functional groups are projecting in
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three dimensions thus producing a rigid spherical core from which to attach the dendrons of interest.
In this study, cyclotriphosphazenes as an important class of inorganic ring systems that
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exhibit different physical and chemical characteristics depending on the properties of the
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reagents and reaction conditions, and BODIPY dyes for its contemporary importance among florescent organic dyes have been selected for the inorganic-organic hybrid systems and prepared the cyclotriphosphazene compounds as the photosensitizer candidate and determined the capacities of their singlet oxygen generation.
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Thus with these considerations, heavy-atom-free BODIPY compounds (B-2 and B3) and their cyclotriphosphazene derivatives (2 and 3) were synthesized. These novel compounds were fully characterized by the standard spectroscopic techniques such as 1
13
C and
31
P NMR, mass spectrometry (MALDI-TOF) and FT-IR spectroscopy and
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elemental analysis as well. Additionally, the photophysical properties of these compounds
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were investigated by using UV-vis and fluorescence spectrophotometers. The singlet oxygen generating capacities of these novels BODIPY substituted cyclotriphosphazene compounds were investigated depends on the addition of an acid solution.
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2. Experimental
2.1. Materials
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All the reactions were performed under an argon atmosphere. Hexachlorocyclotriphosphazene (trimer) was purified by fractional crystallization from n-hexane. Tetrahydrofuran (THF) and toluene were distilled under sodium benzophenone. Analytical thin layer chromatography
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(TLC) was performed on silica gel plates (Merck, Kieselgel 60, 0.25 mm thickness) with F254 indicator. Chromatographic purifications were performed on silica gel (Merck, Kieselgel 60,
spectroscopy
and
the
following
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230-400 mesh) with the indicated eluents. The deuterated solvent (CDCl3) for NMR chemicals
were
obtained
from
Merck;
4-
hydroxybenzaldehyde, triethylamine, boron trifluoride diethyl ether complex (BF3OEt2), piperidine, Cs2CO3, K2CO3, sodium azide, N,N,N′,N′′,N′′-pentamethyldiethylenetriamine
2,4-Dimethyl-1H-pyrrole,
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(PMDTA), dichloromethane, ethylacetate, n-hexane, methanol, toluene and tetrahydrofuran. trifluoroaceticacid
(TFA),
2,3-dichloro-5,6-dicyano-p-
benzoquinone (DDQ) and magnesiumperchlorate [Mg(ClO4)2] were obtained from Sigma-
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Aldrich. 4-dimethylaminobenzaldehyde, 2-bromoethanol, copper (I) bromide, propargyl bromide (80% in toluene, stab. with MgO) was obtained from Alfa-Aesar. Glacial acetic acid, 3,5-dimethoxy-4-hydroxycinnamic acid,
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1,8,9-antracenetriol,
α-cyano-4-hydroxycinnamic
acid and 2,5-dihydroxy benzoic acid for MALDI matrixes were obtained from Fluka. All other reagents and solvents were reagent grade quality and obtained from commercial suppliers. 2.2. Equipment Elemental analyses were carried out using Thermo Finnigan Flash 1112 Instrument. UV-Vis spectra were recorded with a Shimadzu 2001 UV spectrophotometer. Fluorescence excitation
ACCEPTED MANUSCRIPT and emission spectra were recorded on a Varian Eclipse spectrofluorometer using 1 cm pathlength cuvettes at room temperature. Infrared spectra were recorded on a Perkin Elmer Spectrum 100 FT-IR spectrophotometer. Mass spectra were acquired in linear modes with average of 50 shots on a Bruker Daltonics Microflex mass spectrometer (Bremen, Germany)
such
as
1,8,9-antracenetriol,
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equipped with a nitrogen UV-Laser operating at 337 nm. Many different MALDI matrices 3,5-dimethoxy-4-hydroxycinnamic acid,
α-cyano-4-
hydroxycinnamic acid and 2,5-dihydroxy benzoic acid were tried to find an intense molecular
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ion peak and low fragmentation under the MALDI-MS conditions for these compounds. 1,8,9-Anthracenetriol MALDI matrix yielded the best MALDI-MS spectra. 1,8,9-
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Anthracenetriol (20 mg/mL in tetrahydrofuran) matrix for compounds 2 and 3 were prepared. MALDI samples were prepared by mixing compound 2 and 3 were (2 mg/mL in tetrahydrofuran) with the matrix solution (1:10 v/v) in a 0.5 mL Eppendorf micro tube. Finally 1 µL of this mixture was deposited on the sample plate, dried at room temperature and
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then analyzed. Analytical thin layer chromatography (TLC) was performed on silica gel plates (Merck, Kieselgel 60, 0.25 mm thickness) with F254 indicator. Column chromatography was performed on silica gel (Merck, Kieselgel 60, 230-400 mesh; for 3g. crude mixture, 100g
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silica gel was used in a column of 3 cm in diameter and 60 cm in length) and preparative thin 13
C and
31
P NMR spectra
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layer chromatography was performed on silica gel 60 P F254. 1H, were recorded in CDCl3 on a Varian 500 MHz spectrometer.
2.3. Synthesis 4,4’-difluoro-8-(4-propynyloxy)-phenyl-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (B-1) [24], and 2,2,4,4,6,6-hexzakis-(2′-azido-1′-ethoxy)-cyclotriphosphazatriene (1) [25] were prepared and purified according to the literature procedures.
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2.3.1. 4,4’-Difluoro-8-(4-propynyloxy)-phenyl-3,5,7-trimethyl-1-(4-dimethylaminophenyl) ethenyl)-4-bora-3a,4a-diaza-s-indacene (B-2)
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A mixture of BODIPY (B-1) (250 mg, 1 mmol) and dimethylaminobenzaldehyde (98 mg, 1 mmol) were refluxed in a mixture of toluene (50 mL), glacial acetic acid (0.5 mL), piperidine (0.6 mL) and small amount of Mg(ClO4)2. The formed water during the reaction was removed azeotropically by heating overnight in a Dean-Stark apparatus. After this time, the crude
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product was concentrated under vacuum and then was purified by column chromatography
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over silica gel using EtOAc: n-hexane (1:2) solvent system as eluent. The blue colored fraction was collected (150 mg, 0.3 mmol) in 43% yield. (Found: C 72.10, H 5.19, N 8.21 %, C31H30BF2N3O (509.0) requires C 73.09, H 5.94, N 8.25 %). FT-IR (ATR, cm-1) 3300 (C≡CH str), 2919-2857 (-CH str), 1607 (-C=N-), 1545, 1502 (Ar –CH str), 1592 (B-N str), 1365 (B-F str), 1299 (N-CH3), 1171 (-C-O-CH2- str), 1107 (-C-N-C- str). 1H NMR (500
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MHz, CDCl3) δH 7.50 (d, J=8.8, 2H), (Ar-CH), 7.46 (d, J=8.7, 1H), (H-C=C-H), 7.22 (d, 2H, J=8.8), (Ar-CH), 7.18 (d, J=8.7, 1H), (H-C=C-H), 7.08 (d, J=8.7, 2H), (Ar-CH), 6.68 (d,
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J=8.7, 2H), (Ar-CH), 6.59 (s, 2H), (pyrrole-H), 4.76 (d, J=2.4, 2H), (-O-CH2-), 3.02 (s, 6H), (CH3), 2.58 (s, 3H), (CH3), 2.56 (s, 1H), (-C≡H-), 1.47 (s, 3H), (CH3), 1.42 (s, 3H), (CH3)
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ppm. 13C NMR (126 MHz, CDCl3) δC 157.9, 151.0, 144.6, 142.8, 140.3, 137.7, 136.1, 129.9, 129.6, 129.2, 128.4, 124.6, 120.4, 117.6, 116.5, 115.4, 112.0, 110.0, 75.8, 69.3, 63.7, 56.0, 40.2, 14.8, 14.5, 14.4 ppm. MALDI TOF (m/z) Calc. 509.4, Found: 510.0 [M+H]+.
2.3.2. 4,4’-Difluoro-8-(4-propynyloxy)-phenyl-3,5-dimethyl-1,7-bis(4-4’’dimethylaminophenyl) ethenyl)-4-bora-3a,4a-diaza-s-indacene (B-3) According to the above procedure, a mixture of BODIPY (B-1) (250 mg, 1 mmol) and dimethylaminobenzaldehyde (196 mg, 2 mmol) were refluxed in a mixture of toluene (100
ACCEPTED MANUSCRIPT mL), glacial acetic acid (1 mL), piperidine (1.2 mL) and small amount of Mg(ClO4)2. The formed water during the reaction was removed azeotropically by heating overnight in a DeanStark apparatus. After this time, the crude product was concentrated under vacuum and then was purified by column chromatography over silica gel using EtOAc: n-hexane (1:2) solvent
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system as eluent. The green colored fraction was collected (135 mg, 0.2 mmol) in 38 % yield. (Found: C 74.10, H 6.19, N 8.71 %, C40H39BF2N4O (640.5) requires C 75.00, H 6.14, N 8.75 %). FT-IR (ATR, cm-1) 3260 (-C≡CH str), 2904-2857 (-CH str), 1607 (-C=N-), 1584, 1522
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(Ar –CH str), 1478 (B-N str), 1366 (B-F str), 1290 (N-CH3), 1160 (-C-O-CH2- str), 1107 (-CN-C- str). 1H NMR (500 MHz, THF-d8) δH 7.53 (d, J=16.2, 2H), (H-C=C-H), 7.45 (d, J=8.8,
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4H), (Ar-CH), 7.30 (d, J=8.5, 2H), (Ar-CH), 7.22 (d, J=16.1, 2H), (H-C=C-H), 7.14 (d, J=8.5, 2H), (Ar-CH), 6.71 (d, J=8.8, 4H), (Ar-CH), 6.65 (s, 2H), (pyrrole-H), 4.80 (d, J=2.3, 2H), (O-CH2-), 2.76 (s, 1H), (-C≡H-), 1.49 (s, 6H), (CH3), 1.19 (s, 12H), (CH3) ppm.
13
C NMR
(126 MHz, CDCl3) δC 158.1, 153.4, 148.6, 140.6, 136.2, 135.0, 133.4, 130.0, 129.3, 124.5,
640.5, Found: 640.1 [M]+.
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117.3, 115.8, 114.4, 111.5, 109.4, 78.0, 75.8, 55.5, 14.7, 12.0 ppm. MALDI TOF (m/z) Calc.
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2.3.3. Hexakis{4,4’-difluoro-8-(4-propynyloxy)-phenyl-3,5,7-trimethyl-1-(4dimethylaminophenyl)ethenyl)-4-bora-3a,4a-diaza-s-indacene}cyclotriphosphazene (2)
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A solution of 2,2,4,4,6,6-hexzakis-(2′-azido-1′-ethoxy)-cyclotriphosphazatriene (1) (20 mg, 0.031 mmol), BODIPY compound (B-2) (94 mg, 0.18 mmol), copper (I) bromide (40 mg, 0.28 mmol) and PMDTA (32.5 mg, 0.19 mmol) in dry dichloromethane (5 mL) was stirred to give conjugate (2) as a dark blue fraction (35 mg, 0.01 mmol) in 30% yield. (Found: C 64.10, H 5.50, N 14.70 %, C198H204B6F12N39O12P3 (3713.9) requires C 64.04, H 5.70, N 14.71 %). FT-IR (ATR, cm -1) 2950-2919 (-CH str), 2113 (-C=N-), 1457 (-N=N-), 1416 (-N-N-), 1377 (-P- O-), 1235 (-P-N-P-), 1175 (P=N str), 1114 (C-O-C str), 1034, 989 (P-O-C str). 1H NMR
ACCEPTED MANUSCRIPT (500 MHz, CDCl3) δH 7.50 (d, J=8.8, 12H), (Ar-CH), 7.47 (d, J=8.7, 6H), (H-C=C-H), 7.28 (s, 6H), (-N-C-H), 7.22 (d, J=8.8, 12H), (Ar-CH), 7.18 (d, J=8.7, 6H), (H-C=C-H), 7.09 (d, J=8.7, 12H), (Ar-CH), 6.68 (d, J=8.7, 12H), (Ar-CH), 6.59 (s, 12H), (pyrrole-H), 3.50 (s, 12H), (O-CH2), 3.02 (s, 36H), (N-CH3), 2.58 (s, 18H), (CH3), 2.23 (t, 12H), (-H2C-CH2), 1.85
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(t, 12H), (-H2C-CH2), 1.47 (s, 18H), (CH3), 1.42 (s, 18H), (CH3) ppm. 13C NMR (126 MHz, CDCl3) δC 162.7, 157.6, 151.4, 143.6, 143.3, 139.0, 138.4, 133.2, 129.7, 129.5, 129.2, 127.4, 122.2, 116.7, 115.2, 114.3, 72.4, 67.1, 66.0, 55.4, 27.2, 26.2, 17.7 ppm. 31P{1H} NMR (500
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MHz, CDCl3) δP 17.40 (s) ppm. MALDI TOF (m/z) Calc. 3707.8, Found: 3708.4 [M]+, 3688.6
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[M-F]+.
2.3.4. Hexakis{4,4’-difluoro-8-(4-propynyloxy)-phenyl-3,5-dimethyl-1,7-bis(4-4’’dimethylaminophenyl)ethenyl)-4-bora-3a,4a-diaza-s-indacene} cyclotriphosphazene (3) According to the above procedure, a solution of 2,2,4,4,6,6-hexzakis-(2′-azido-1′-ethoxy)-
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cyclotriphosphazatriene (1) (20 mg, 0.031 mmol), BODIPY compound (3) (118 mg, 0.23 mmol), copper (I) bromide (41 mg, 0.29 mmol) and PMDTA (32.5 mg, 0.19 mmol) in dry dichloromethane (5 mL) was stirred to give conjugate (3) as a dark green fraction (30 mg,
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0.01 mmol) in 22% yield. Found: C 67.12, H 5.60, N 14.20 %, C252H258B6F12N45O12P3 (4500.0) requires C 67.25, H 5.91, N 14.00 %). FT-IR (ATR, cm -1) 2915-2849 (-CH str),
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2109 (-C=N-), 1469 (-N=N-), 1417 (-N-N-), 1377 (-P- O-), 1234 (-P-N-P-), 1177 (P=N str), 1100 (C-O-C str), 1046, 990 (P-O-C str). 1H NMR (500 MHz, CDCl3) δH 7.52 (d, J=8.7, 24H), (Ar-CH), 7.48 (d, J=8.8, 12H), (H-C=C-H), 7.26 (s, 6H), (-N-C-H), 7.23 (d, J=8.7, 12H), (Ar-CH), 7.17 (d, J=8.8, 12H), (H-C=C-H), 7.07 (d, J=8.8, 12H), (Ar-CH), 6.66 (d, J=8.8, 24H), (Ar-CH), 6.58 (s, 12H), (pyrrole-H), 3.50 (s, 12H), (O-CH2-), 3.08 (s, 72H), (NCH3), 2.21 (t, 12H), (-H2C-CH2), 1.85 (t, 12H), (-H2C-CH2), 1.45 (s, 36H), (CH3), ppm. 13C NMR (126 MHz, CDCl3) δC 160.7, 159.6, 150.4, 145.6, 145.3, 139.0, 138.4, 133.2, 129.7,
ACCEPTED MANUSCRIPT 129.5, 129.2, 127.4, 122.2, 116.7, 115.2, 114.3, 72.4, 67.1, 66.0, 55.4, 27.2, 26.2 ppm. 31
P{1H} NMR (500 MHz, CDCl3) δP 17.41 (s) ppm. MALDI TOF (m/z) Calc. 4494.9, Found:
4495.0 [M]+ and 4475.9 [M-F]+.
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3. Results and Discussion 3.1.Synthesis and Characterization
Two BODIPY dyes B-2 and B-3 were designed (Scheme 1). BODIPY was selected as the
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chromophore due to its excellent photophysical properties, such as strong absorption of visible light, high fluorescence quantum yields, good photostability and the feasibly
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derivatizable molecular structure [7, 26-27]. The synthetic route to the target compounds 2 and 3 is depicted in Scheme 2. Compound 2 and 3 were synthesized by using ‘click’ reactions. BODIPY compounds B-2 and B-3 were characterized by using elemental analysis, FT-IR, mass, 1H and 13C NMR spectroscopy techniques. Compounds 2 and 3 were 13
C and
31
P NMR
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characterized also by using elemental analysis, FT-IR, mass, 1H, spectroscopy techniques. 1H and
13
C NMR spectrums of BODIPY compounds are similar to
each other. In addition, 1H and 13C NMR and 31P NMR spectrums of phosphazene compounds
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are also similar to each other. All of the spectrums were given in supporting information.
3.2. UV−Vis Absorption and Fluorescence Experiments
The absorption and fluorescence properties of compounds 2 and 3 have been studied in different solvents such as dichloromethane, methanol, toluene and THF. Molar absorptivity of these compounds in different solvents given in Table 1. The maximum absorption and fluorescence signals of the compounds were obtained in THF. Then photophysical properties
ACCEPTED MANUSCRIPT of the compounds investigated in THF at room temperature with 2x10-6 M concentration. The fluorescence quantum yields (ΦF) of compound 2 and 3 were determined by the comparative method (Eq. (1)) [28]. ி.ೄ .మ
∅ܨ∅ = ܨௌ௧ௗ ி
(1)
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మ ೄ ..ೄ
where F and FStd are the areas under the fluorescence emission curves of the compound 2, compound 3 and the standard. A and AStd are the respective absorbances of compound 2, compound 3 and the standard at the excitation wavelengths. The refractive indices (n) of the
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solvents were employed in calculating the fluorescence quantum yields in different solvents.
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Methylene blue (in methanol) (ΦF = 0.03) [29] were employed as the standard. Fluorescence quantum yields of compounds 2 and 3 were found 0.01 and 0.03 in THF, respectively. UV-vis absorption and emission spectra were given in Fig. 2a for compounds 2 and B2, and Fig. 2b for compounds 3 and B-3. According to Fig. 2a, the maximum absorption bands were observed at 600 nm and 602 nm for BODIPY compound B-2 and its phosphazene
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counterpart 2, respectively due to the mono-styryl BODIPY moieties. The fluorescence emission maxima were observed at 654 nm and 658 nm (Excitation wavelength=600 nm) for
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these compounds, respectively. On the other hand, the maximum absorption bands of B-3 and its phosphazene counterpart 3 were observed at 691 nm and 692 nm respectively due to the
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di-styryl BODIPY moieties. The fluorescence emission maxima were observed at 727 nm and 728 nm (Excitation wavelength=640 nm) for these compounds, respectively.
3.2. Variation of the UV−Vis Absorption and the Fluorescence Emission Spectra Upon Protonation In order to study the effect of protonation on the photophysical properties, the UV-vis absorption and the fluorescence emission spectra of the compounds B-2, B-3, 2 and 3 were
ACCEPTED MANUSCRIPT studied after addition of 10 µM strong acid (0.5mM perchloric acid, HClO4) and after addition of 10 µM strong base (0.5mM potassium tert-butoxide, C4H9KO) [30]. The addition of aqueous C4H9KO solution didn’t show any effect the absorption and emission bands of the studied compounds except for a little decreasing in the intensities of the bands. But, both
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absorption and emission peaks were completely disappeared and new bands formations for each compounds were observed after addition of aqueous HClO4 solution due to the protonation of the nitrogen atoms on the dimethylamino groups (Fig. 3). According to Fig. 3a,
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the absorption band of B-2 at 600 nm was diminished completely and a new absorption band was observed at 558 nm. On the other hand, the emission band of this compound at 654 nm
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also completely diminished and a new fluorescence band at 567 nm was observed concomitantly. The same effect was observed for the phosphazene counterpart of this BODIPY compound. While the absorption band was disappeared at 602 nm for 2, the new band was observed at 566 nm in the UV-Vis spectra after addition of small amount aqueous
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HClO4 solution. Similarly, the emission band of 2 at 658 nm was also diminished and a new fluorescence band was observed at 568 nm in its fluorescence spectra. Similar results were observed for compounds B-3 and 3, and related spectra were given in Fig. 3c and Fig. 3d,
BODIPY
core
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respectively. These results indicated that internal charge transfer (ICT) occurred between and
dimethylaminobenzyl
groups
and
the
absorption
band
of
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dimethylaminostyryl BODIPY compounds (B-2 and B-3) and their phosphazene derivatives (2 and 3) showed blue-shifts and this is reasonable since the ICT effect was diminished after protonation of the nitrogen atoms on the dimethylamine groups. Aqueous HClO4 or C4H9KO solutions were also added the hexa-borondipyrromethene cyclotriphosphazene compound linked via triazole groups (HBTC) which synthesized according to our previous study [31] for determination of the protonation ability of nitrogen atoms on the triazole ring. It is suggesting that the nitrogen atoms on the triazole ring did not show protonation because any changes did
ACCEPTED MANUSCRIPT not observe their electronic absorption and fluorescence spectra after addition of acid or base to the solution of HBTC (Fig. S1, Supplementary data).
3.3. Singlet Oxygen (1O2) Production
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The singlet oxygen (1O2) generations of the studied compounds were measured in THF with 5x10-6 M concentration. These productions of these compounds were also determined after addition of acid. The 1,3-diphenylisobenzofuran (DPBF) was used as quencher for
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determination of the produced singlet oxygen [32] in THF. The singlet oxygen generation of the starting BODIPY compounds (B-2 and B-3) was also measured for comparison the effect
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of substitution of these groups to phosphazene ring. The light irradiations at 600 nm for B-2 and 2, and 700 nm for B-3 and 3 were used for singlet oxygen production by used studied compounds. The absorption bands of all studied compounds (B-2, B-3, 2 and 3) did not show any changes when the absorption band of DPBF at 417 nm reduced by light irradiation which
light irradiation.
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indicated that the compounds did not decompose during singlet oxygen studies under used
The starting compounds (B-2 and B-3) and their cyclotriphosphazene derivatives (2
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and 3) showed low singlet oxygen generation in THF due to ICT effect between BODIPY core and dimethylaminobenzyl groups (Figs. S2, S4, S6, S8, Supplementary data). Upon
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addition of 10 µM aqueous solution of HClO4 to the solutions of the studied compounds, significant 1O2 production was observed using same light irradiations, indicated by the tremendous decreasing of the absorbance of DPBF at 417 nm after addition of acid (Figs. S3, S5, S7, S9, Supplementary data). The absorbance values of DPBF were plotted versus irradiation time for all studied compounds to compare the 1O2 production for these compounds in the absence and in the presence of aqueous solution of HClO4, (Figs. 4a, 4b and 4c). The singlet oxygen generation of all studied compounds was increased after addition of
ACCEPTED MANUSCRIPT acid. While the singlet oxygen generation of the starting mono-styryl BODIPY (B-2) increased 43.5-fold, the cyclotriphosphazene counterpart (2) was produced 63-fold singlet oxygen after addition of acid (Fig. 4a). On the other hand, the increasing of the singlet oxygen generation by the addition of acid was found much higher for di-sytryl substituted derivatives
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(B-3 and 3). The di-styryl BODIPY compound (B-3) produced 51-fold singlet oxygen after addition of acid but a dramatic increasing was observed for di-styryl BODIPY substituted cyclotriphosphazene compound (3) (Fig. 4b). This compound was produced 413-fold singlet
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oxygen after addition of acid (Fig. 4b). The substitution of the mono- and di-BODIPY compounds to the cyclotriphosphazene ring occurred higher singlet oxygen generated novel
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photosensitizers (Fig. 4c).
These results indicate that synthesized heavy-atom free compounds (B-2, 2, B-3 and 3) in this study, can be potential photosensitizers to be used for the singlet oxygen generation. Cyclotriphosphazene-BODIPY conjugates (2 and 3) are generating more singlet oxygen than
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their starting BODIPY compounds. It could be due to the increasing number of BODIPY moieties on phosphazene ring. On the other hand, the compound 3 is more suitable than
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compound 2 because of the excess number of styryl groups on the compound 3.
4. Conclusion
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In this study, new BODIPY-cyclotriphosphazene compounds 2 and 3 were synthesized for the first time. These novel compounds were fully characterized by different spectroscopic methods such as FT-IR, 1H NMR, 13C NMR, 31P NMR, UV-Vis, mass and elemental analysis as well. Photophysical properties such as fluorescence and singlet oxygen generation were investigated in their THF solutions. All these heavy atom free compounds showed very limited fluorescence emission and singlet oxygen generation due to the internal charge transfer (ICT) occurred between BODIPY core and dimethylaminobenzyl groups. These
ACCEPTED MANUSCRIPT properties were also determined by the protonation of the studied compounds. Both fluorescence emission and singlet oxygen generation behaviors of the studied compounds were dramatically increased after addition of acid because the ICT effect was blocked due to the protonation of the nitrogen atoms on the dimethylamine groups. It is suggesting that the
used as efficient singlet oxygen generators.
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References
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novel cyclotriphosphazene-BODIPY conjugates are potential photosensitizers that can be
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[14] Topel Demirel S, Turgut Cin G, Akkaya EU. Near IR excitation of heavy atom free Bodipyphotosensitizers through the intermediacy of upconverting nanoparticles. Chem
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ACCEPTED MANUSCRIPT [18] Allcock HR. Phosphorus Nitrogen Compounds: Cyclic, Linear and High Polymeric Systems. Academic Press, 1972.
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emission: a unimolecular, emission-mode, molecular halfsubtractor with reconfigurable logic
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2057−68.
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N N
B
F
F
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(B-2)
N O
N
O
H
F
B
N F
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N
AcOH/Piperidine Toluene Reflux Dean-stark trap
O
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(B-1)
N N
B
F
F
N
(B-3) N
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Scheme 1. Synthetic pathway of BODIPY compounds B-2 and B-3.
Scheme 2. Synthetic pathway of BODIPY substituted cyclotriphosphazene compounds 2 and 3.
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Fig. 1. Chemical structures of BODIPY substituted cyclotriphosphazene compounds 2 and 3.
Table 1. Molar absorptivities (ε) of the compound 2 and 3 in different solvents
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Compound Molar THF Absorptivity ε (L.mol28520 2 1 .cm-1) ε (L.mol21160 3 1 .cm-1)
CH2Cl2
Methanol
Toluene
Cyclohexane Water
9980
2820
6770
insoluble
insoluble
7606.2
5866.5
9952.8
insoluble
insoluble
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Fig. 2. Electronic absorption and fluorescence emission spectra of a) compounds B-2 and 2 (Excitation wavelength=600 nm), b) compounds B-3 and 3 in THF (Excitation wavelength=640 nm).
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Fig. 3. Variation of the UV-vis absorption spectra of a) B-2, b) 2, c) B-3 and d) 3 after addition of aqueous solutions of C4H9KO and HClO4.
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a)
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b)
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c)
Fig. 4. Absorbance of DPBF versus time graphs of a) B-2 and 2, b) B-3 and 3, c) 2
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and 3 before and after addition of acid.
ACCEPTED MANUSCRIPT Highlights •Synthesis and characterization of cyclotriphosphazene-BODIPY conjugates. •Determination of the photophysical and photochemical properties. •Heavy-atom-free photosensitizers.
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•Highly singlet oxygen generation capability.
S0143-7208(16)30820-8
DOI:
10.1016/j.dyepig.2016.12.035
Reference:
DYPI 5660
To appear in:
Dyes and Pigments
Received Date: 25 September 2016 Revised Date:
10 December 2016
Accepted Date: 15 December 2016
Please cite this article as: Çetindere S, Tümay SO, Kılıç A, Durmuş M, Yeşilot S, Synthesis and physicochemical properties of cyclotriphosphazene-BODIPY conjugates, Dyes and Pigments (2017), doi: 10.1016/j.dyepig.2016.12.035. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Synthesis and physico-chemical properties of cyclotriphosphazene-BODIPY conjugates Seda Çetindere, Süreyya Oğuz Tümay, Adem Kılıç, Mahmut Durmuş, Serkan Yeşilot*
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Contribution from:
Department of Chemistry, Gebze Technical University, Gebze, Kocaeli, Turkey
Author for correspondence:
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*
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Professor Serkan YEŞİLOT, Department of Chemistry, Gebze Technical University, P.O.Box: 141, Gebze 41400, Kocaeli, Turkey Tel:
00 90 262 6053014
Fax:
00 90 262 6053005
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e-mail : [email protected]
ACCEPTED MANUSCRIPT
Abstract
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The novel cyclotriphosphazene compounds bearing mono- and distyryl BODIPY substituents were synthesized and characterized by the standard spectroscopic techniques such as 1H, 13C and 31P NMR, mass spectrometry (MALDITOF) and FT-IR spectroscopy and elemental analysis as well. The photophysical properties of these novel cyclotriphosphazene compounds
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were investigated in tetrahydrofuran (THF) solutions. The singlet oxygen generation ability of these compounds was also investigated depends on the addition of an acid solution. It was found that the singlet oxygen producing ability of the dyes was dramatically increased
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under the acidic conditions when compared to the initial state, and these results indicate that
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these dyes can be potential singlet oxygen photosensitizers.
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Keywords: Cyclotriphosphazene, BODIPY, Singlet Oxygen, Photophysical, Photochemical
ACCEPTED MANUSCRIPT 1. Introduction Photosensitized generation of singlet oxygen (1O2) is a well-studied phenomenon, which has found various applications from synthetic organic chemistry such as ene reactions, hetero Diels Alder reaction, [2+2] cycloaddition reactions [1-2] and photodynamic therapy (PDT) [3-
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4]. The generation of singlet oxygen in solution requires a photosensitizer (PS) which is converted to the triplet excited state (intersystemcrossing, ISC) upon irradiation. Many dyes obtained from natural or synthetic sources with a high intersystem crossing (ISC) have been
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used for reactions of singlet oxygen and PDT. Nowadays boradiazaindacene (BODIPY) dyes show superior sensitizer properties due to their long wavelength excitability, good solubility
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and non-toxicity behaviors and high singlet oxygen generation capacity [5, 6]. The heavy atom effect has been a useful chemical approach to improve ISC in several molecules including BODIPY chromophores [7-8]. But intersystem crossing (ISC) without heavy atoms can only be accomplished by a limited number of BODIPY photosensitizers; hence,
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substantial effort is dedicated to the search of novel compounds and strategies [9-14]. However, the photoinduced electron transfer (PET) is one of the most popular mechanisms to switch the singlet excited state of organic chromophores [15] such as BODIPY [16].
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Concerning the controlling of the triplet excited states, O’shea and his co-workers previously studied the acid-activated PDT effect of the azaBodipy derivatives under neutral and acidic
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conditions [17]. Protonation of the amino moiety on BODIPY compounds may inhibit the PET, as a result the 1O2 photosensitizing ability may be enhanced. This molecular designing rational is based on the study of the PET modulated fluorescence [15]. Cyclotriphosphazenes are an interesting class of materials with a planar nondelocalized cyclic ring consisting of alternating N and P atoms. The inorganic phosphazenes have been well studied by several groups due to their diverse properties including excellent hydrolytic stability, thermal stability, flame retardant properties and
ACCEPTED MANUSCRIPT liquid crystalline behavior [18-23]. The cyclotriphosphazene core (CP) serves many advantageous. For example the chemistry to prepare functionalized CP cores is very straightforward, the functionalized CP cores are very stable and do not breakdown even under very aggressive chemical conditions and the functional groups are projecting in
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three dimensions thus producing a rigid spherical core from which to attach the dendrons of interest.
In this study, cyclotriphosphazenes as an important class of inorganic ring systems that
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exhibit different physical and chemical characteristics depending on the properties of the
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reagents and reaction conditions, and BODIPY dyes for its contemporary importance among florescent organic dyes have been selected for the inorganic-organic hybrid systems and prepared the cyclotriphosphazene compounds as the photosensitizer candidate and determined the capacities of their singlet oxygen generation.
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Thus with these considerations, heavy-atom-free BODIPY compounds (B-2 and B3) and their cyclotriphosphazene derivatives (2 and 3) were synthesized. These novel compounds were fully characterized by the standard spectroscopic techniques such as 1
13
C and
31
P NMR, mass spectrometry (MALDI-TOF) and FT-IR spectroscopy and
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H,
elemental analysis as well. Additionally, the photophysical properties of these compounds
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were investigated by using UV-vis and fluorescence spectrophotometers. The singlet oxygen generating capacities of these novels BODIPY substituted cyclotriphosphazene compounds were investigated depends on the addition of an acid solution.
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2. Experimental
2.1. Materials
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All the reactions were performed under an argon atmosphere. Hexachlorocyclotriphosphazene (trimer) was purified by fractional crystallization from n-hexane. Tetrahydrofuran (THF) and toluene were distilled under sodium benzophenone. Analytical thin layer chromatography
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(TLC) was performed on silica gel plates (Merck, Kieselgel 60, 0.25 mm thickness) with F254 indicator. Chromatographic purifications were performed on silica gel (Merck, Kieselgel 60,
spectroscopy
and
the
following
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230-400 mesh) with the indicated eluents. The deuterated solvent (CDCl3) for NMR chemicals
were
obtained
from
Merck;
4-
hydroxybenzaldehyde, triethylamine, boron trifluoride diethyl ether complex (BF3OEt2), piperidine, Cs2CO3, K2CO3, sodium azide, N,N,N′,N′′,N′′-pentamethyldiethylenetriamine
2,4-Dimethyl-1H-pyrrole,
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(PMDTA), dichloromethane, ethylacetate, n-hexane, methanol, toluene and tetrahydrofuran. trifluoroaceticacid
(TFA),
2,3-dichloro-5,6-dicyano-p-
benzoquinone (DDQ) and magnesiumperchlorate [Mg(ClO4)2] were obtained from Sigma-
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Aldrich. 4-dimethylaminobenzaldehyde, 2-bromoethanol, copper (I) bromide, propargyl bromide (80% in toluene, stab. with MgO) was obtained from Alfa-Aesar. Glacial acetic acid, 3,5-dimethoxy-4-hydroxycinnamic acid,
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1,8,9-antracenetriol,
α-cyano-4-hydroxycinnamic
acid and 2,5-dihydroxy benzoic acid for MALDI matrixes were obtained from Fluka. All other reagents and solvents were reagent grade quality and obtained from commercial suppliers. 2.2. Equipment Elemental analyses were carried out using Thermo Finnigan Flash 1112 Instrument. UV-Vis spectra were recorded with a Shimadzu 2001 UV spectrophotometer. Fluorescence excitation
ACCEPTED MANUSCRIPT and emission spectra were recorded on a Varian Eclipse spectrofluorometer using 1 cm pathlength cuvettes at room temperature. Infrared spectra were recorded on a Perkin Elmer Spectrum 100 FT-IR spectrophotometer. Mass spectra were acquired in linear modes with average of 50 shots on a Bruker Daltonics Microflex mass spectrometer (Bremen, Germany)
such
as
1,8,9-antracenetriol,
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equipped with a nitrogen UV-Laser operating at 337 nm. Many different MALDI matrices 3,5-dimethoxy-4-hydroxycinnamic acid,
α-cyano-4-
hydroxycinnamic acid and 2,5-dihydroxy benzoic acid were tried to find an intense molecular
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ion peak and low fragmentation under the MALDI-MS conditions for these compounds. 1,8,9-Anthracenetriol MALDI matrix yielded the best MALDI-MS spectra. 1,8,9-
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Anthracenetriol (20 mg/mL in tetrahydrofuran) matrix for compounds 2 and 3 were prepared. MALDI samples were prepared by mixing compound 2 and 3 were (2 mg/mL in tetrahydrofuran) with the matrix solution (1:10 v/v) in a 0.5 mL Eppendorf micro tube. Finally 1 µL of this mixture was deposited on the sample plate, dried at room temperature and
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then analyzed. Analytical thin layer chromatography (TLC) was performed on silica gel plates (Merck, Kieselgel 60, 0.25 mm thickness) with F254 indicator. Column chromatography was performed on silica gel (Merck, Kieselgel 60, 230-400 mesh; for 3g. crude mixture, 100g
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silica gel was used in a column of 3 cm in diameter and 60 cm in length) and preparative thin 13
C and
31
P NMR spectra
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layer chromatography was performed on silica gel 60 P F254. 1H, were recorded in CDCl3 on a Varian 500 MHz spectrometer.
2.3. Synthesis 4,4’-difluoro-8-(4-propynyloxy)-phenyl-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (B-1) [24], and 2,2,4,4,6,6-hexzakis-(2′-azido-1′-ethoxy)-cyclotriphosphazatriene (1) [25] were prepared and purified according to the literature procedures.
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2.3.1. 4,4’-Difluoro-8-(4-propynyloxy)-phenyl-3,5,7-trimethyl-1-(4-dimethylaminophenyl) ethenyl)-4-bora-3a,4a-diaza-s-indacene (B-2)
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A mixture of BODIPY (B-1) (250 mg, 1 mmol) and dimethylaminobenzaldehyde (98 mg, 1 mmol) were refluxed in a mixture of toluene (50 mL), glacial acetic acid (0.5 mL), piperidine (0.6 mL) and small amount of Mg(ClO4)2. The formed water during the reaction was removed azeotropically by heating overnight in a Dean-Stark apparatus. After this time, the crude
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product was concentrated under vacuum and then was purified by column chromatography
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over silica gel using EtOAc: n-hexane (1:2) solvent system as eluent. The blue colored fraction was collected (150 mg, 0.3 mmol) in 43% yield. (Found: C 72.10, H 5.19, N 8.21 %, C31H30BF2N3O (509.0) requires C 73.09, H 5.94, N 8.25 %). FT-IR (ATR, cm-1) 3300 (C≡CH str), 2919-2857 (-CH str), 1607 (-C=N-), 1545, 1502 (Ar –CH str), 1592 (B-N str), 1365 (B-F str), 1299 (N-CH3), 1171 (-C-O-CH2- str), 1107 (-C-N-C- str). 1H NMR (500
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MHz, CDCl3) δH 7.50 (d, J=8.8, 2H), (Ar-CH), 7.46 (d, J=8.7, 1H), (H-C=C-H), 7.22 (d, 2H, J=8.8), (Ar-CH), 7.18 (d, J=8.7, 1H), (H-C=C-H), 7.08 (d, J=8.7, 2H), (Ar-CH), 6.68 (d,
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J=8.7, 2H), (Ar-CH), 6.59 (s, 2H), (pyrrole-H), 4.76 (d, J=2.4, 2H), (-O-CH2-), 3.02 (s, 6H), (CH3), 2.58 (s, 3H), (CH3), 2.56 (s, 1H), (-C≡H-), 1.47 (s, 3H), (CH3), 1.42 (s, 3H), (CH3)
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ppm. 13C NMR (126 MHz, CDCl3) δC 157.9, 151.0, 144.6, 142.8, 140.3, 137.7, 136.1, 129.9, 129.6, 129.2, 128.4, 124.6, 120.4, 117.6, 116.5, 115.4, 112.0, 110.0, 75.8, 69.3, 63.7, 56.0, 40.2, 14.8, 14.5, 14.4 ppm. MALDI TOF (m/z) Calc. 509.4, Found: 510.0 [M+H]+.
2.3.2. 4,4’-Difluoro-8-(4-propynyloxy)-phenyl-3,5-dimethyl-1,7-bis(4-4’’dimethylaminophenyl) ethenyl)-4-bora-3a,4a-diaza-s-indacene (B-3) According to the above procedure, a mixture of BODIPY (B-1) (250 mg, 1 mmol) and dimethylaminobenzaldehyde (196 mg, 2 mmol) were refluxed in a mixture of toluene (100
ACCEPTED MANUSCRIPT mL), glacial acetic acid (1 mL), piperidine (1.2 mL) and small amount of Mg(ClO4)2. The formed water during the reaction was removed azeotropically by heating overnight in a DeanStark apparatus. After this time, the crude product was concentrated under vacuum and then was purified by column chromatography over silica gel using EtOAc: n-hexane (1:2) solvent
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system as eluent. The green colored fraction was collected (135 mg, 0.2 mmol) in 38 % yield. (Found: C 74.10, H 6.19, N 8.71 %, C40H39BF2N4O (640.5) requires C 75.00, H 6.14, N 8.75 %). FT-IR (ATR, cm-1) 3260 (-C≡CH str), 2904-2857 (-CH str), 1607 (-C=N-), 1584, 1522
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(Ar –CH str), 1478 (B-N str), 1366 (B-F str), 1290 (N-CH3), 1160 (-C-O-CH2- str), 1107 (-CN-C- str). 1H NMR (500 MHz, THF-d8) δH 7.53 (d, J=16.2, 2H), (H-C=C-H), 7.45 (d, J=8.8,
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4H), (Ar-CH), 7.30 (d, J=8.5, 2H), (Ar-CH), 7.22 (d, J=16.1, 2H), (H-C=C-H), 7.14 (d, J=8.5, 2H), (Ar-CH), 6.71 (d, J=8.8, 4H), (Ar-CH), 6.65 (s, 2H), (pyrrole-H), 4.80 (d, J=2.3, 2H), (O-CH2-), 2.76 (s, 1H), (-C≡H-), 1.49 (s, 6H), (CH3), 1.19 (s, 12H), (CH3) ppm.
13
C NMR
(126 MHz, CDCl3) δC 158.1, 153.4, 148.6, 140.6, 136.2, 135.0, 133.4, 130.0, 129.3, 124.5,
640.5, Found: 640.1 [M]+.
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117.3, 115.8, 114.4, 111.5, 109.4, 78.0, 75.8, 55.5, 14.7, 12.0 ppm. MALDI TOF (m/z) Calc.
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2.3.3. Hexakis{4,4’-difluoro-8-(4-propynyloxy)-phenyl-3,5,7-trimethyl-1-(4dimethylaminophenyl)ethenyl)-4-bora-3a,4a-diaza-s-indacene}cyclotriphosphazene (2)
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A solution of 2,2,4,4,6,6-hexzakis-(2′-azido-1′-ethoxy)-cyclotriphosphazatriene (1) (20 mg, 0.031 mmol), BODIPY compound (B-2) (94 mg, 0.18 mmol), copper (I) bromide (40 mg, 0.28 mmol) and PMDTA (32.5 mg, 0.19 mmol) in dry dichloromethane (5 mL) was stirred to give conjugate (2) as a dark blue fraction (35 mg, 0.01 mmol) in 30% yield. (Found: C 64.10, H 5.50, N 14.70 %, C198H204B6F12N39O12P3 (3713.9) requires C 64.04, H 5.70, N 14.71 %). FT-IR (ATR, cm -1) 2950-2919 (-CH str), 2113 (-C=N-), 1457 (-N=N-), 1416 (-N-N-), 1377 (-P- O-), 1235 (-P-N-P-), 1175 (P=N str), 1114 (C-O-C str), 1034, 989 (P-O-C str). 1H NMR
ACCEPTED MANUSCRIPT (500 MHz, CDCl3) δH 7.50 (d, J=8.8, 12H), (Ar-CH), 7.47 (d, J=8.7, 6H), (H-C=C-H), 7.28 (s, 6H), (-N-C-H), 7.22 (d, J=8.8, 12H), (Ar-CH), 7.18 (d, J=8.7, 6H), (H-C=C-H), 7.09 (d, J=8.7, 12H), (Ar-CH), 6.68 (d, J=8.7, 12H), (Ar-CH), 6.59 (s, 12H), (pyrrole-H), 3.50 (s, 12H), (O-CH2), 3.02 (s, 36H), (N-CH3), 2.58 (s, 18H), (CH3), 2.23 (t, 12H), (-H2C-CH2), 1.85
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(t, 12H), (-H2C-CH2), 1.47 (s, 18H), (CH3), 1.42 (s, 18H), (CH3) ppm. 13C NMR (126 MHz, CDCl3) δC 162.7, 157.6, 151.4, 143.6, 143.3, 139.0, 138.4, 133.2, 129.7, 129.5, 129.2, 127.4, 122.2, 116.7, 115.2, 114.3, 72.4, 67.1, 66.0, 55.4, 27.2, 26.2, 17.7 ppm. 31P{1H} NMR (500
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MHz, CDCl3) δP 17.40 (s) ppm. MALDI TOF (m/z) Calc. 3707.8, Found: 3708.4 [M]+, 3688.6
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[M-F]+.
2.3.4. Hexakis{4,4’-difluoro-8-(4-propynyloxy)-phenyl-3,5-dimethyl-1,7-bis(4-4’’dimethylaminophenyl)ethenyl)-4-bora-3a,4a-diaza-s-indacene} cyclotriphosphazene (3) According to the above procedure, a solution of 2,2,4,4,6,6-hexzakis-(2′-azido-1′-ethoxy)-
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cyclotriphosphazatriene (1) (20 mg, 0.031 mmol), BODIPY compound (3) (118 mg, 0.23 mmol), copper (I) bromide (41 mg, 0.29 mmol) and PMDTA (32.5 mg, 0.19 mmol) in dry dichloromethane (5 mL) was stirred to give conjugate (3) as a dark green fraction (30 mg,
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0.01 mmol) in 22% yield. Found: C 67.12, H 5.60, N 14.20 %, C252H258B6F12N45O12P3 (4500.0) requires C 67.25, H 5.91, N 14.00 %). FT-IR (ATR, cm -1) 2915-2849 (-CH str),
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2109 (-C=N-), 1469 (-N=N-), 1417 (-N-N-), 1377 (-P- O-), 1234 (-P-N-P-), 1177 (P=N str), 1100 (C-O-C str), 1046, 990 (P-O-C str). 1H NMR (500 MHz, CDCl3) δH 7.52 (d, J=8.7, 24H), (Ar-CH), 7.48 (d, J=8.8, 12H), (H-C=C-H), 7.26 (s, 6H), (-N-C-H), 7.23 (d, J=8.7, 12H), (Ar-CH), 7.17 (d, J=8.8, 12H), (H-C=C-H), 7.07 (d, J=8.8, 12H), (Ar-CH), 6.66 (d, J=8.8, 24H), (Ar-CH), 6.58 (s, 12H), (pyrrole-H), 3.50 (s, 12H), (O-CH2-), 3.08 (s, 72H), (NCH3), 2.21 (t, 12H), (-H2C-CH2), 1.85 (t, 12H), (-H2C-CH2), 1.45 (s, 36H), (CH3), ppm. 13C NMR (126 MHz, CDCl3) δC 160.7, 159.6, 150.4, 145.6, 145.3, 139.0, 138.4, 133.2, 129.7,
ACCEPTED MANUSCRIPT 129.5, 129.2, 127.4, 122.2, 116.7, 115.2, 114.3, 72.4, 67.1, 66.0, 55.4, 27.2, 26.2 ppm. 31
P{1H} NMR (500 MHz, CDCl3) δP 17.41 (s) ppm. MALDI TOF (m/z) Calc. 4494.9, Found:
4495.0 [M]+ and 4475.9 [M-F]+.
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3. Results and Discussion 3.1.Synthesis and Characterization
Two BODIPY dyes B-2 and B-3 were designed (Scheme 1). BODIPY was selected as the
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chromophore due to its excellent photophysical properties, such as strong absorption of visible light, high fluorescence quantum yields, good photostability and the feasibly
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derivatizable molecular structure [7, 26-27]. The synthetic route to the target compounds 2 and 3 is depicted in Scheme 2. Compound 2 and 3 were synthesized by using ‘click’ reactions. BODIPY compounds B-2 and B-3 were characterized by using elemental analysis, FT-IR, mass, 1H and 13C NMR spectroscopy techniques. Compounds 2 and 3 were 13
C and
31
P NMR
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characterized also by using elemental analysis, FT-IR, mass, 1H, spectroscopy techniques. 1H and
13
C NMR spectrums of BODIPY compounds are similar to
each other. In addition, 1H and 13C NMR and 31P NMR spectrums of phosphazene compounds
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are also similar to each other. All of the spectrums were given in supporting information.
3.2. UV−Vis Absorption and Fluorescence Experiments
The absorption and fluorescence properties of compounds 2 and 3 have been studied in different solvents such as dichloromethane, methanol, toluene and THF. Molar absorptivity of these compounds in different solvents given in Table 1. The maximum absorption and fluorescence signals of the compounds were obtained in THF. Then photophysical properties
ACCEPTED MANUSCRIPT of the compounds investigated in THF at room temperature with 2x10-6 M concentration. The fluorescence quantum yields (ΦF) of compound 2 and 3 were determined by the comparative method (Eq. (1)) [28]. ி.ೄ .మ
∅ܨ∅ = ܨௌ௧ௗ ி
(1)
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మ ೄ ..ೄ
where F and FStd are the areas under the fluorescence emission curves of the compound 2, compound 3 and the standard. A and AStd are the respective absorbances of compound 2, compound 3 and the standard at the excitation wavelengths. The refractive indices (n) of the
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solvents were employed in calculating the fluorescence quantum yields in different solvents.
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Methylene blue (in methanol) (ΦF = 0.03) [29] were employed as the standard. Fluorescence quantum yields of compounds 2 and 3 were found 0.01 and 0.03 in THF, respectively. UV-vis absorption and emission spectra were given in Fig. 2a for compounds 2 and B2, and Fig. 2b for compounds 3 and B-3. According to Fig. 2a, the maximum absorption bands were observed at 600 nm and 602 nm for BODIPY compound B-2 and its phosphazene
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counterpart 2, respectively due to the mono-styryl BODIPY moieties. The fluorescence emission maxima were observed at 654 nm and 658 nm (Excitation wavelength=600 nm) for
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these compounds, respectively. On the other hand, the maximum absorption bands of B-3 and its phosphazene counterpart 3 were observed at 691 nm and 692 nm respectively due to the
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di-styryl BODIPY moieties. The fluorescence emission maxima were observed at 727 nm and 728 nm (Excitation wavelength=640 nm) for these compounds, respectively.
3.2. Variation of the UV−Vis Absorption and the Fluorescence Emission Spectra Upon Protonation In order to study the effect of protonation on the photophysical properties, the UV-vis absorption and the fluorescence emission spectra of the compounds B-2, B-3, 2 and 3 were
ACCEPTED MANUSCRIPT studied after addition of 10 µM strong acid (0.5mM perchloric acid, HClO4) and after addition of 10 µM strong base (0.5mM potassium tert-butoxide, C4H9KO) [30]. The addition of aqueous C4H9KO solution didn’t show any effect the absorption and emission bands of the studied compounds except for a little decreasing in the intensities of the bands. But, both
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absorption and emission peaks were completely disappeared and new bands formations for each compounds were observed after addition of aqueous HClO4 solution due to the protonation of the nitrogen atoms on the dimethylamino groups (Fig. 3). According to Fig. 3a,
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the absorption band of B-2 at 600 nm was diminished completely and a new absorption band was observed at 558 nm. On the other hand, the emission band of this compound at 654 nm
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also completely diminished and a new fluorescence band at 567 nm was observed concomitantly. The same effect was observed for the phosphazene counterpart of this BODIPY compound. While the absorption band was disappeared at 602 nm for 2, the new band was observed at 566 nm in the UV-Vis spectra after addition of small amount aqueous
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HClO4 solution. Similarly, the emission band of 2 at 658 nm was also diminished and a new fluorescence band was observed at 568 nm in its fluorescence spectra. Similar results were observed for compounds B-3 and 3, and related spectra were given in Fig. 3c and Fig. 3d,
BODIPY
core
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respectively. These results indicated that internal charge transfer (ICT) occurred between and
dimethylaminobenzyl
groups
and
the
absorption
band
of
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dimethylaminostyryl BODIPY compounds (B-2 and B-3) and their phosphazene derivatives (2 and 3) showed blue-shifts and this is reasonable since the ICT effect was diminished after protonation of the nitrogen atoms on the dimethylamine groups. Aqueous HClO4 or C4H9KO solutions were also added the hexa-borondipyrromethene cyclotriphosphazene compound linked via triazole groups (HBTC) which synthesized according to our previous study [31] for determination of the protonation ability of nitrogen atoms on the triazole ring. It is suggesting that the nitrogen atoms on the triazole ring did not show protonation because any changes did
ACCEPTED MANUSCRIPT not observe their electronic absorption and fluorescence spectra after addition of acid or base to the solution of HBTC (Fig. S1, Supplementary data).
3.3. Singlet Oxygen (1O2) Production
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The singlet oxygen (1O2) generations of the studied compounds were measured in THF with 5x10-6 M concentration. These productions of these compounds were also determined after addition of acid. The 1,3-diphenylisobenzofuran (DPBF) was used as quencher for
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determination of the produced singlet oxygen [32] in THF. The singlet oxygen generation of the starting BODIPY compounds (B-2 and B-3) was also measured for comparison the effect
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of substitution of these groups to phosphazene ring. The light irradiations at 600 nm for B-2 and 2, and 700 nm for B-3 and 3 were used for singlet oxygen production by used studied compounds. The absorption bands of all studied compounds (B-2, B-3, 2 and 3) did not show any changes when the absorption band of DPBF at 417 nm reduced by light irradiation which
light irradiation.
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indicated that the compounds did not decompose during singlet oxygen studies under used
The starting compounds (B-2 and B-3) and their cyclotriphosphazene derivatives (2
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and 3) showed low singlet oxygen generation in THF due to ICT effect between BODIPY core and dimethylaminobenzyl groups (Figs. S2, S4, S6, S8, Supplementary data). Upon
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addition of 10 µM aqueous solution of HClO4 to the solutions of the studied compounds, significant 1O2 production was observed using same light irradiations, indicated by the tremendous decreasing of the absorbance of DPBF at 417 nm after addition of acid (Figs. S3, S5, S7, S9, Supplementary data). The absorbance values of DPBF were plotted versus irradiation time for all studied compounds to compare the 1O2 production for these compounds in the absence and in the presence of aqueous solution of HClO4, (Figs. 4a, 4b and 4c). The singlet oxygen generation of all studied compounds was increased after addition of
ACCEPTED MANUSCRIPT acid. While the singlet oxygen generation of the starting mono-styryl BODIPY (B-2) increased 43.5-fold, the cyclotriphosphazene counterpart (2) was produced 63-fold singlet oxygen after addition of acid (Fig. 4a). On the other hand, the increasing of the singlet oxygen generation by the addition of acid was found much higher for di-sytryl substituted derivatives
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(B-3 and 3). The di-styryl BODIPY compound (B-3) produced 51-fold singlet oxygen after addition of acid but a dramatic increasing was observed for di-styryl BODIPY substituted cyclotriphosphazene compound (3) (Fig. 4b). This compound was produced 413-fold singlet
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oxygen after addition of acid (Fig. 4b). The substitution of the mono- and di-BODIPY compounds to the cyclotriphosphazene ring occurred higher singlet oxygen generated novel
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photosensitizers (Fig. 4c).
These results indicate that synthesized heavy-atom free compounds (B-2, 2, B-3 and 3) in this study, can be potential photosensitizers to be used for the singlet oxygen generation. Cyclotriphosphazene-BODIPY conjugates (2 and 3) are generating more singlet oxygen than
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their starting BODIPY compounds. It could be due to the increasing number of BODIPY moieties on phosphazene ring. On the other hand, the compound 3 is more suitable than
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compound 2 because of the excess number of styryl groups on the compound 3.
4. Conclusion
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In this study, new BODIPY-cyclotriphosphazene compounds 2 and 3 were synthesized for the first time. These novel compounds were fully characterized by different spectroscopic methods such as FT-IR, 1H NMR, 13C NMR, 31P NMR, UV-Vis, mass and elemental analysis as well. Photophysical properties such as fluorescence and singlet oxygen generation were investigated in their THF solutions. All these heavy atom free compounds showed very limited fluorescence emission and singlet oxygen generation due to the internal charge transfer (ICT) occurred between BODIPY core and dimethylaminobenzyl groups. These
ACCEPTED MANUSCRIPT properties were also determined by the protonation of the studied compounds. Both fluorescence emission and singlet oxygen generation behaviors of the studied compounds were dramatically increased after addition of acid because the ICT effect was blocked due to the protonation of the nitrogen atoms on the dimethylamine groups. It is suggesting that the
used as efficient singlet oxygen generators.
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References
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novel cyclotriphosphazene-BODIPY conjugates are potential photosensitizers that can be
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2057−68.
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N N
B
F
F
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(B-2)
N O
N
O
H
F
B
N F
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N
AcOH/Piperidine Toluene Reflux Dean-stark trap
O
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(B-1)
N N
B
F
F
N
(B-3) N
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Scheme 1. Synthetic pathway of BODIPY compounds B-2 and B-3.
Scheme 2. Synthetic pathway of BODIPY substituted cyclotriphosphazene compounds 2 and 3.
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Fig. 1. Chemical structures of BODIPY substituted cyclotriphosphazene compounds 2 and 3.
Table 1. Molar absorptivities (ε) of the compound 2 and 3 in different solvents
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Compound Molar THF Absorptivity ε (L.mol28520 2 1 .cm-1) ε (L.mol21160 3 1 .cm-1)
CH2Cl2
Methanol
Toluene
Cyclohexane Water
9980
2820
6770
insoluble
insoluble
7606.2
5866.5
9952.8
insoluble
insoluble
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Fig. 2. Electronic absorption and fluorescence emission spectra of a) compounds B-2 and 2 (Excitation wavelength=600 nm), b) compounds B-3 and 3 in THF (Excitation wavelength=640 nm).
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Fig. 3. Variation of the UV-vis absorption spectra of a) B-2, b) 2, c) B-3 and d) 3 after addition of aqueous solutions of C4H9KO and HClO4.
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a)
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b)
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c)
Fig. 4. Absorbance of DPBF versus time graphs of a) B-2 and 2, b) B-3 and 3, c) 2
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and 3 before and after addition of acid.
ACCEPTED MANUSCRIPT Highlights •Synthesis and characterization of cyclotriphosphazene-BODIPY conjugates. •Determination of the photophysical and photochemical properties. •Heavy-atom-free photosensitizers.
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•Highly singlet oxygen generation capability.