Novel intramolecular π-π-interaction in a BODIPY system by oxidation of a single selenium center: geometrical stamping and spectroscopic and spectrometric distinctions

Article abstract of DOI:10.1039/c7dt00555e

A new BODIPY system displaying an intramolecular π-π-interaction was synthesized and studied. When the selenium center was oxidized, the substituted phenyl group undergoes π-π stacking with one side of the BODIPY core. The oxidized form showed, not only a down-field shift in the NMR peak, but also splitting due to geometrical changes that arise when going from C_s to C₁. The compound was characterized by X-ray diffraction; DFT methods helped elucidate the influence of the unexpected π-π stack and its connection to the photophysical properties imparted by the Se oxidation.

Full text of DOI:10.1039/c7dt00555e

View Article Online
View Journal
Dalton
Transactions
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. Kim, T. Jun, S.
V. Mulay, S. T. Manjare, J. Kwak, Y. Lee and D. G. Churchill, Dalton Trans., 2017, DOI:
10.1039/C7DT00555E.
This is an Accepted Manuscript, which has been through the
Volume 45 Number
1 7 January 2016 Pages 1–398
Royal Society of Chemistry peer review process and has been
accepted for publication.
Dalton
Transactions
Accepted Manuscripts are published online shortly after
An international journal of inorganic chemistry
www.rsc.org/dalton
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-9226
PAPER
Joseph T. Hupp, Omar K. Farha et al.
Efficient extraction of sulfate from water using
framework
a Zr-metal–organic
rsc.li/dalton

Please do not adjust margins
Dalton Transactions
Page 1 of 7
View Article Online
DOI: 10.1039/C7DT00555E
Journal Name
ARTICLE
Novel intramolecular π-π-interaction in a BODIPY system by
oxidation of a single selenium center: geometrical stamping and
spectroscopic and spectrometric distinctions
Received 00th January 20xx,
Accepted 00th January 20xx
Youngsam Kim,a,b Taehong Jun,a Sandip V. Mulay,b Sudesh T. Manjare,c Jinseong Kwak,d Yunho
Leed and David G. Churchilla,b*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A new BODIPY system displaying an intramolecular π-π-interaction was synthesized and studied. When the selenium
center was oxidized, the substituted phenyl group undergoes π-π stacking with one side of the BODIPY core. The oxidized
form showed, not only a down-field shift in the NMR peak, but also splitting due to geometrical changes that arise when
going from Cs to C1. The compound was characterized by X-ray diffraction; DFT methods helped elucidate the influence of
the unexpected π-π stack and its connection to the photophysical properties imparted by the Se oxidation.
etc. In the field of molecular chemosening, organoselenium
compounds are useful for dynamic measurements of
biologically important analytes. In particular, chemical redox
Introduction
Organoselenium chemistry has developed rapidly since the
1970s, even though the first organoselenium compound was
synthesized in the middle of the 18th century. This lag may be
due in part to the malodorous nature, instability, and difficult
purification of the compounds involved.1 Organoselenium
chemistry has been rapidly receiving increased attention due
to its various roles and redox properties and the relatively low
state of toxicity compared to inorganic selenium compounds.
Recently, a number of reports have increased in the fields of
electroconducting materials and catalysis.2 The biochemical
importance of organoselenium compounds has been
investigated after the enzymatic and biological roles such as
glutathione peroxidase (GPx) were discovered and clarified.3
Accordingly, organoselenium compounds have progressed to
various fields such as the pharmaceutical scene, medicinal
chemistry, bacterial enzymology due to its properties, e.g.
antioxidant,3a, 4 antitumor,5 and antimicrobial activity.6 More
recently, organoselenium compounds have been exploited in
chemodosimeter and chemosensor research for the detection
of important biology-based analytes, as well as for reactive
oxygen species (ROS)/reactive nitrogen species (RNS), biothiols
properties enable the attribute of reversible detection:
oxidation with ROS and reduction with e.g. biothiols.7
In the past two decades, the field of and use of emissive
organic dyes has been widely extended for diagnostics,
electroluminescent devices, labelling DNA/proteins, analyte
sensing and so on; these techniques offer advantages such as
high sensitivity, rapid response, non-invasive detection, and in-
vivo biological cellular imaging.8 As one class of important
fluorophore, the usage of 4,4-difluoro-4-bora-3a,4a-diaza-s-
indacene (BODIPY)-based systems has consistently increased
due to the available benefit which include sharp excitation
peaks and emission wavelengths, high quantum yields,
photostability in physiological conditions, and
a relative
insensitivity to the solution environment.9 Therefore,
continued modification of BODIPY dyes has become one of the
potentially workable and usable frameworks of importance in
the chemosensing literature.
In terms of photophysical properties, intermolecular
interactions are noteworthy for their ability to ease and
effectively help change the photomechanism. In different
solvents, molecular interactions would affect the
photophysical properties with several specific molecular
features impacted by the environment including e.g. polarity
and viscosity.10 The BODIPY system, in general, shows fairly
different photochemical and electrochemical properties
depending on whether inter- or intramolecular interactions are
available and whether they are engaged or disengaged.11 For
these reasons, intermolecular forces and interactions have
been more of a constant focus. While there are many
examples of inter/intramolecular interactions in polymer
derivatives12 and fluorophore systems,13 intramolecular π-π-
interactions between a substituted group and a fluorophore
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 2 of 7
View Article Online
DOI: 10.1039/C7DT00555E
ARTICLE
Journal Name
core are rare. Herein, they are discussed as being on important crystal was coated with Paratone-N oil and mounted on a
focal point, accompanied by clear and abundant spectroscopic DualThickness MicroLoops LD purchased from MiTeGen. The
evidence.
data were collected with graphite monochromated Mo (Kα)
radiation (λ = 0.71073 Å) at 120 K. Cell parameters were
determined and refined as done routinely by the SMART
software program. Data reduction was performed using SAINT
software. An empirical absorption correction was applied using
the SADABS program.
Synthesis of 2,5-dibromothiophene-3-carboxaldehyde (1).
Compound
procedure.14
1 was synthesized by a known literature
Synthesis
of
5-bromo-2-(phenylselanyl)-thiophene-3-
stirred solution of diphenyl
carboxaldehyde (2). To
a
diselenide (1.25 g, 4.0 mmol) in anhydrous ethanol (30 mL)
was added NaBH4 (0.3 g, 8.0 mmol) at 0°C under N2
atmosphere. Then, the reaction mixture was warmed to room
temperature and stirred for an additional 30 min. The reaction
mixture then changed from yellow to colorless; then, 2,5-
dibromothiophene-3-carboxaldehyde (1.08 g, 4.0 mmol) was
added to the reaction mixture. The reaction mixture was
stirred for 3 hr at room temperature. The reaction was
monitored by TLC. After complete consumption of starting
material, the solvent was evaporated under reduced pressure.
Water (20 mL) was then added to the residue, and the residue
mixture was extracted with CH2Cl2 (3 × 25 mL). Combined
organic layers were washed with brine (25 mL), dried over
Na2SO4 and concentrated under reduced pressure. The crude
product was purified by silica gel column chromatography
using EtOAc / hexane (5:95) as the eluent. Yield: 0.8 g, 58%; 1H
NMR (600 MHz, CDCl3): δ 9.93 (s, 1H6), 7.61 (dd, 3JH-H = 8.0 Hz,
4JH-H = 1.4 Hz, 2H8), 7.41-7.39 (m, 1H10), 7.38-7.35 (m, 2H9),
7.36 (s, 1H4); 13C NMR (150.87 MHz, CDCl3): δ 184.2 (C6), 144.5
(C2), 139.5 (C3), 134.7 (C8), 130.6 (C4), 130.1 (C9), 129.6 (C10),
128.6 (C7), 113.8 (C5); 77Se NMR (76.3 MHz, CDCl3): δ 418.2.
Scheme 1. Synthesis of compounds (1 to 5 and 7 to 9).
Experimental section
Materials All chemicals and materials used herein were used
as received from commercial suppliers (Aldrich, Tokyo
chemical Industry and Junsei chemical companies) and used
without further purification. Thin layer chromatography (TLC)
was performed on DC Kieselgel 60 F254 silica gel plates.
DFT calculations The molecular structures and HOMO-LUMO
levels of the probe and oxidized version of the compound were
estimated using density functional theory (DFT) calculations
[by Gaussian 09 program (B3LYP method with 6-311g* basis
set for Se and Br only and 6-31g* basis set for all other
atoms).] All calculations were performed with the gas phase.
Synthesis
substituted BODIPY (3). 2,4–Dimethylpyrrole (476 mg, 5.0
mmol) and 5-bromo-2-(phenylselanyl)thiophene-3-
Spectroscopic data 1H, 13C, 11B, 19F, 77Se and 2D (HMBC and carboxaldehyde (692 mg,
mmol) were mixed into
of
5-bromo-2-(phenylselanyl)-thiophene-
2
HSQC) NMR spectra were acquired using a Bruker Avance 400
and Agilent-NMR-vnmrs 600 MHz spectrometer. TMS and
dimethylselenide were used as external standards. Absorption
dichloromethane. Then, TFA (trifluoroacetic acid) was added
to the reaction mixture and stirred at room temperature.
After 1 hr, DDQ (2,3–dichloro–5,6–dicyano–1,4–benzoquinone,
545 mg, 2.4 mmol) was added to the reaction mixture. While
stirring for 1 hr at room temperature, BF3·OEt2 (2.5 ml, 20
mmol) and triethylamine were added to achieve basic solution
conditions. This reaction mixture was stirred at room
temperature for 12 hrs. After this time, the volatiles were then
removed by rotary evaporation. The residue was re-dissolved
into ethyl acetate and washed with an aqueous NaHCO3
solution. The organic layer was dried over anhydrous MgSO4
and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography using
spectra were measured using
a
JASCO V–530
spectrophotometer. Fluorescence measurements were carried
out with a Shimadzu RF–5301 pc spectrofluorophotometer.
Spectrometric data ESI-mass spectrometry was performed on
a BRUKER micrOTOF-QⅡ by the research support staff at
KAIST. A Time-of-Flight mass spectrometer was operated at a
resolution of 20,000.
X-ray Crystallography The diffraction data of compound 4 was
collected on a Bruker D8 QUEST. A suitable size and quality of
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 3 of 7
View Article Online
DOI: 10.1039/C7DT00555E
Journal Name
dichloromethane / hexane (1:1) as the eluent. Yield: 276 mg,
ARTICLE
24%; 1H NMR (600 MHz, CD2Cl2): δ 7.51 (d, 3JH-H = 7.0 Hz, 2H20), Synthesis of (2,5-dibromothiophen-3-yl)methanol (7).16 To a
7.30 (t, 3JH-H = 7.4 Hz, 1H22), 7.20 (t, 3JH-H = 7.7 Hz, 2H21), 6.90 (s, stirred solution of 2,5-dibromothiophene-3-carboxaldehyde
1H16), 5.98 (s, 2H2,6), 2.53 (s, 6H12,14), 1.48 (s, 6H11,13); 13C NMR (101 mg, 0.370 mmol) in anhydrous ethanol (3.0 mL) was
(150.87 MHz, CD2Cl2): δ 156.5 (C3,5), 143.3 (C8,10), 139.6 (C9), added NaBH4 (14.2 mg, 0.370 mmol) at 0°C under N2
135.9 (C20), 134.8 (C18), 131.7 (C1,7), 131.4 (C16), 129.7 (C21), atmosphere. Then, the reaction mixture was warmed to room
129.5 (C22), 128.2 (C19), 126.0 (C15), 121.7 (C2,6), 116.8 (C17), temperature and stirred for an additional 5 hr. The reaction
14.8 (C12,14), 13.9 (C11,13); 11B NMR (128.34 MHz, CD2Cl2): δ 0.56 was monitored by TLC. After complete consumption of the
(t, JB–F = 32.8 Hz); 19F NMR (376.38 MHz, CD2Cl2): δ –146.1 (q, starting material, solvent was then evaporated under reduced
JB–F = 32.8 Hz); 77Se NMR (CD2Cl2): δ 344.4; HRMS (ESI) (m/z): pressure. Water was added to the residue, and the mixture
[M + Na]+ calc. for C23H20BBrF2N2SSe + Na: 586.9655, found: was summarily extracted with CH2Cl2. Combined organic layers
586.9694.
were washed with brine, dried over Na2SO4 and concentrated
under reduced pressure. The crude product was purified by
Synthesis of (4). To a stirred solution of compound 3 (56 mg, column chromatography using EtOAc / hexane (1:9) as the
0.10 mmol) in CH2Cl2 (5 mL) was added m-CPBA (17 mg, 0.10 eluent. Yield: 94.5 mg, 94 %; 1H NMR (400 MHz, CDCl3): δ 6.93
mmol) at room temperature. After stirring for 30 min at this (s, 1H), 4.45 (s, 2H), 3.39 (s, 1H); 13C NMR (101 MHz, CDCl3): δ
temperature, the solvent was removed by rotary evaporation. 141.3, 130.5, 111.5, 109.2, 59.0.
The crude residue was purified by silica gel column
chromatography using EtOAc / hexane (1:1) as the eluent. Synthesis of 2,5-dibromothiophene-substituted BODIPY (8).
Yield: 30 mg, 52 %; 1H NMR (600 MHz, CD2Cl2): δ 7.55 (d, 3JH-H
=
2,4–Dimethylpyrrole (233 mg, 2.5 mmol) and 2,5-
6.2 Hz, 2H21), 7.45 (td, JH-H = 7.6 Hz, 4JH-H = 2.5 Hz, 1H22), 7.38 dibromothiophene-3-carboxaldehyde (300 mg, 1.1 mmol)
(td, 3JH-H = 7.6 Hz, 4JH-H = 2.6 Hz, 2H20), 7.00 (d, J = 2.6 Hz, 1H16), were mixed in dichloromethane. Then, TFA (trifluoroacetic
6.14 (s, 1H6), 5.84 (s, 1H2), 2.56 (s, 3H14), 2.53 (s, 3H12), 1.78 (s, acid) was added to the reaction mixture and stirred at room
3H13), 1.11 (s, 3H11); 13C NMR (150.87 MHz, CD2Cl2): δ 158.2 temperature. After 1 hr, DDQ (2,3–dichloro–5,6–dicyano–1,4–
(C5), 157.5 (C3), 144.6 (C15), 143.7 (C8), 143.4 (C10), 141.5 (C19), benzoquinone, 272.4 mg, 1.2 mmol) was added to the reaction
137.7 (C18), 132.5 (C22), 132.2 (C16), 131.5 (C9), 131.4 (C1), 131.3 mixture. While stirring for 1 hr at room temperature, BF3·OEt2
(C7), 130.2 (C20), 126.3 (C21), 122.7 (C6), 122.2(C2), 120.0 (C17), (0.822 ml, 6.00 mmol) and triethylamine were added to
15.1 (C14), 15.0 (C12) 14.3 (C13), 13.9 (C11); 11B NMR (128.34 achieve basic solution conditions. The reaction mixture was
MHz, CD2Cl2): δ 0.51 (t, JB–F = 32.2 Hz); 19F NMR (376.38 MHz, then stirred for 12 hrs at room temperature. After this time,
3
2
1
CD2Cl2): δ –145.6 (dq, JF–F = 107.9 Hz, JB–F = 32.8 Hz), –146.3 the volatiles were removed by rotary evaporation. The residue
2
1
(dq, JF–F = 107.9 Hz, JB–F = 32.7 Hz); 77Se NMR (76.3 MHz, was re-dissolved in ethyl acetate and washed with aqueous
CD2Cl2): δ 865.9; HRMS (ESI) (m/z): [M + Na]+ calc. for NaHCO3 solution. The organic layer was dried over anhydrous
C23H20BBrF2N2OSSe + Na: 602.9604, found: 602.9643.
MgSO4 and was then concentrated under reduced pressure.
The residue was purified by silica gel column chromatography
Synthesis of 5-bromothiophene-3-carbaldehyde (5).15 To a using EtOAc / hexane (5:95) as the eluent. Yield: 88 mg, 16%;
stirred solution of diphenyl ditelluride (303 mg, 0.740 mmol) in 1H NMR (600 MHz, CDCl3): δ 6.85 (s, 1H16), 6.02 (s, 2H2,6), 2.55
anhydrous ethanol (6 mL) was added NaBH4 (30.4 mg, 0.800 (s, 6H12,14), 1.69 (s, 6H11,13); 13C NMR (150.87 MHz, CDCl3): δ
mmol) at 0°C under N2 atmosphere. Then, the reaction mixture 156.8 (C3,5), 142.6 (C8,10), 136.2 (C15), 132.6 (C9) 131.2 (C1,7),
was warmed to room temperature and stirred for an 130.4 (C16), 121.7 (C2,6), 113.5 (C18), 111.8 (C17), 14.9 (C12,14),
additional 30 min. The reaction mixture was changed from 13.6 (C11,13); 11B NMR (128.34 MHz, CDCl3): δ 0.55 (t, JB–F = 32.9
2
reddish-yellow to colorless and then 2,5-dibromothiophene-3- Hz); 19F NMR (376.38 MHz, CDCl3): δ –145.8 (dq, JF–F = 109.5
carboxaldehyde (201 mg, 0.740 mmol) was added to the Hz, 1JB–F = 33.1 Hz), –146.6 (dq, 2JF–F = 109.5 Hz, 1JB–F = 32.3 Hz);
reaction mixture. The reaction mixture was stirred for 3 hr at HRMS (ESI) (m/z): [M + Na]+ calc. for C17H15BBr2F2N2S + Na:
the same temperature. The reaction was monitored by TLC. 510.9261, found: 510.9442.
After complete consumption of the starting material, the
solvent was evaporated under reduced pressure. Water was Synthesis of 5-bromothiophene-substituted BODIPY (9). To a
then added to the residue, and subsequently extracted with stirred solution of diphenyl ditelluride (25.2 mg, 0.062 mmol)
CH2Cl2. Combined organic layers were washed with brine, in anhydrous and degassed ethanol (3.0 mL) was added NaBH4
dried over Na2SO4 and was concentrated under reduced (4.7 mg, 0.12 mmol) at 0°C under N2 atmosphere. Then
pressure. The crude product was purified by silica gel column reaction mixture was warmed to room temperature and
chromatography using EtOAc / hexane (5:95) as the eluent. stirred for an additional 30 min. The reaction mixture changed
Yield: 102.1 mg, 72 %; 1H NMR (600 MHz, CDCl3): δ 9.74 (s, 1H), from reddish-yellow to colorless; after this time compound
7.98 (s, 1H), 7.46 (s, 1H); 13C NMR (150.87 MHz, CDCl3): δ (30.0 mg, 0.062 mmol) was added to the reaction mixture. The
8
183.6, 143.1, 137.9, 127.8, 115.1.
reaction mixture was stirred for 3 hr at room temperature. The
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 4 of 7
View Article Online
DOI: 10.1039/C7DT00555E
ARTICLE
Journal Name
reaction was monitored by TLC. After complete consumption
of the starting material, the solvent was evaporated under
the aliphatic region, peaks splitting the 1- and 3-position
methyl groups of the BODIPY system (signal for 3-position was
reduced pressure. Water was then added to the residue, and centered at δ 2.53 ppm and moved to δ 2.56 and 2.53 ppm,
that for the 1-position, moved from δ 1.48 ppm to δ 1.78 and
1.11 ppm), were observed (Figures 2, S5 and S11). Also, there
were concomitant shifts in the carbon NMR signals. The 13C
NMR signal of methyl groups has become clearly split from
two to four peaks (from δ 14.8 ppm to δ 15.1 and 15.0 ppm;
from δ 13.9 ppm to 13.9 and 14.3 ppm). The methine group of
13C NMR spectral peaks changed from δ 121.7 ppm to δ 122.7
and 122.2 ppm (Figures S5 and S11). In the case of 19F NMR
spectroscopic data, splitting of the fluorine NMR spectroscopic
this layer was then extracted with CH2Cl2. Combined organic
layers were washed with brine, dried over Na2SO4 and
concentrated under reduced pressure. The crude product was
purified by silica gel column chromatography using EtOAc /
hexane (1:50) as the eluent. Yield: 18.3 mg, 75 %; 1H NMR (600
4
4
MHz, CDCl3): δ 7.44 (d, JH-H = 5.6 Hz, 1H18), 6.83 (d, JH-H = 5.6
Hz, 1H16), 6.01 (s, 2H2,6), 2.56 (s, 6H12,14), 1.59 (s, 6H11,13); 13C
NMR (150.87 MHz, CDCl3): δ 156.4 (C3,5), 142.8 (C8,10), 135.5
(C15), 134.4 (C9), 131.4 (C1,7), 128.4 (C18), 128.0 (C16), 121.4
(C2,6), 112.4 (C17), 14.8 (C12), 13.3 (C11); 11B NMR (128.34 MHz,
CDCl3): δ 0.62 (t, JB–F = 32.9 Hz); 19F NMR (376.38 MHz, CDCl3):
signal was observed. The 19F NMR spectrum of compound
3
showed a quartet at δ –146.1 (q, 1JB–F = 32.8 Hz) corresponding
to the BF2–group signal (Figure S6). The mono-oxidation of the
2
1
δ –146.3 (dq, JF–F = 106.7 Hz, JB–F = 33.4 Hz); HRMS (ESI)
(m/z): [M + Na]+ calc. for C17H16BBrF2N2S + Na: 431.0176,
433.0156, found: 431.0263, 433.0243.
sole selenium center then induced formation of a doublet of
2
doublet of quartets of signals centered at δ –145.6 (dq, JF–F
=
1
2
1
107.9 Hz, JB–F = 32.8 Hz), δ –146.3 (dq, JF–F = 107.9 Hz, JB–F
=
32.7Hz). The splitting and general appearance of the 11B NMR
spectrum peaks, however, do not change significantly upon
chemical oxidation (Figures S12).
Results and discussion
Previously, BODIPY organochalcogen-substituents in meso-
positions have been developed and reported.17 As reported
previously, organochalcogen substitutions impact special
properties: fluorescent quenchers by PET process,18 oxidation
with ROS/RNS16 and reversible reactions with biothiols.17a-d, 20
Based on the synthetic details in these previous reports,
compound
3 was synthesized for potential sensing system in
the anticipation of allowing for its use as a key component of a
reversible detection of ROS, in particular hypochlorite
Figure 1. Spectroscopic changes of 1H NMR by oxidation.
detection (Scheme 1). Compound 3 showed selective detection
for hypochlorite over other ROS. While obtaining
spectroscopic and spectrometric data of the oxidized version
of
3 to confirm the structural changes and photo-mechanism,
NMR spectroscopic peak splittings were observed in the 1H
1
NMR spectrum. The splitting of H NMR peaks is not observed
in meso-chalcogen-substituted BODIPY systems. A possibility
of by-product formation was ruled out since close integer ratio
and symmetry of the splitting patterns existed. To explain
these phenomena, the reaction of
agent, e.g. m-CPBA, and further purification were performed
to obtain compound on preparative scale (Scheme 1). High
3 with a strong oxidizing
4
Figure 2. Molecular structure of compound 4. Crystallographic
resolution mass spectrometric data (HRMS) was acquired as a
first point in analysis. The mass spectrometric results showed
calculated (M/Z) values for both compounds matched the
parameters (CCDC# 1000278): a = 8.9526(2) Å, b = 10.2532(3)
Å, c = 14.7976(4) Å, α = 94.4778(14)°, β = 106.8774(12)°, γ =
114.9387(12)°.
experimentally obtained values for compound
586.9694) and compound (M/Z = 602.9643) (Figures S17-
S18). After Se oxidation was identified by HRMS, 77Se NMR
spectral data of compound was recorded to better confirm
3 (M/Z =
4
As compared with reports of unsymmetrical and annulated
BODIPY systems, the NMR spectroscopic data for compound
4
4
showed unusual splittings. Based on this splitting, the
integration of the NMR spectral peaks were not able to be
caused by only a rotational hindrance of ring current effects
and simple transformations. Therefore, we hypothesized (i)
the symmetry of the compound converted to Cs symmetric
energetically to a static non-symmetric C1 form, and (ii) other
inter- or intra- interactions must exist.
the oxidation of the selenium center. As expected, the oxidized
selenium center showed a downfield shift of δ 865.9 ppm,
compared to the original value of δ 344.4 ppm confirming the
formation of a tetravalent center17b, 17d, 20a, 21 (Figures S7 and
S13). Then, a comparison of 1H NMR spectra between
compounds
3 and 4
was carefully carried out. The 1H NMR
peak of the methine group in BODIPY was split from one (δ
5.98 ppm) to two different signals (δ 6.14 and 5.84 ppm). In
To confirm our hypothesis and to eliminate other
possibilities,
4
was characterized by X-ray crystallography
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 5 of 7
View Article Online
DOI: 10.1039/C7DT00555E
Journal Name
ARTICLE
(Figure 2, Tables S1 and S2). Compound
4
featured an same orientation as oxidation
4, the dihedral angle was even
intramolecular planar π–π stacking interaction between one greater than the dihedral angle found for that in optimized 4
side of the fluorophore largely involving (i) one entire pyrrolyl The geometric differences among and optimized 4/4’
group, and (ii) the entire aryl group of the PhSe- group. The support π-π-stacking between PhSe- and the BODIPY core for
planar systems are linked by four atoms with a Phcent–Pyrcent compound and oxidation as a causative factor for the
distance of 3.69 Å. The dihedral angle between the stacking formation.
phenylselenium plane and the BODIPY core is 7.9 Upon π-π-stacking between the oxidized PhSe- and BODIPY
corresponding to nearly parallel positioning. Such an skeleton in compound the targeted phenyltelluride
intramolecular π–π stack system has neither been reported analogue 10), expected to have similar chemical and
.
3, 4
4
˚
a
4,
(
between any fluorophore / chromophore-type group nor for photophysical properties, was sought via synthesis by
any phenylchalcogen-substituted group to the best of our analogous synthetic methods (Scheme 1). The reaction of
knowledge. The desymmetrization (Cs
intramolecular π-π-interaction caused the observed conditions as those for the synthesis of
spectroscopic changes. Secondarily, selenium was mono- ; surprisingly, compound was obtained instead in 72% yield
ꢀ
C1) and compound
1
with diphenylditelluride under the same
3
was expected to give
6
5
oxidized and bears the expected pyramidal geometry (C–Se–C (Figures S19-S21). To understand the role of the
angle of 96.7(1)°) which assisted in adopting the unique phenyltelluride for dehalogenation, several control
intramolecular effect.
experiments were carried out. Compound
1 was treated with
NaBH4; as expected, the aldehyde was reduced to alcohol
7
(Figure S22). Even excess amounts of NaBH4 were insufficient
to effect debromination. The other control experiment with
diphenylditelluride did not show changes; virtually all starting
material was recovered. Accordingly, 2,5-dibromothiophene
meso-substituted BODIPY (
8) was synthesized and allowed us
to perform the debromination reaction with phenyltelluride in
the presence of NaBH4 to give the telluride analogue (10
)
(Figures S23-S27).
Under the above-mentioned reaction conditions, 5-
bromothiophene BODIPY ( ) was obtained (73 %) (Figures S28-
S32). In an analogous reaction of with diphenyldiselenide
with NaBH4 under the same conditions, starting materials (
9
8
8)
were recovered (Scheme 1). In previous related reports,
telluride and selenide derivatives undergo substitution
reactions with aryl compounds under similar conditions.22
While only a few examples showed dehalogenation, however,
aryl compounds contain phenol groups that undergo dienone-
phenol rearrangements.23 Based on control experiments, and
bolstered by findings from related reports, phenyltelluride
undergoes reaction to become substituted with the 2-
bromothiophene moiety; however, it seems that the in situ
generated phenyltelluride analogue is rapidly substituted by
hydride. This is driven partly because of bond strength
differences: C–Te and H–Te have bond enthalpies
approximately 30-40 kJ mol-1 greater than those for C–Se and
H–Se bonds.24
Figure 3. Dihedral angles between PhSe-plane and BODIPY
plane of 3, 4 and optimized 4 / 4’ (C’s and Se were picked for
the PhSe- plane and C’s, N and B were picked to represent the
BODIPY plane).
Density functional theory (DFT) calculations were exploited
to help elucidate π-π-stacking. Calculations were carried out
with the geometry optimized structure of
B3LYP/6-31g* basis set (6-311g* for Se/Br). Furthermore, the
structure of was also calculated by optimization. Compound
was calculated twice in two different orientations of the
3 with the use of the
The original aim of preparing
3 was to study the reversible
4
detection of ROS by discrete redox chemistry changes at the
selenium center. As with analogous sulfide chemistry, it is well-
known that a selenium-centered probe can be oxidized with
hypochlorite resulting in ‘turn-on’ fluorescence by a blocking
4
oxidized group corresponding to the geometries labelled
optimized 4/4’. Dihedral angles between the PhSe and BODIPY
were compared among 3, 4 and optimized 4/4’. To build up
of the PET process.7 Compound
3 shows a strong green
two planes for analysis, carbon and the selenium atoms were
chosen on oxidized PhSe and carbon, nitrogen and boron
atoms belonging to the BODIPY core were used. As mentioned
fluorescent enhancement after addition of hypochlorite. Then,
a screening test was performed with various ROS such as KO2,
H2O2, BuOOH, NaOCl, ONOO- in the presence of compound
t
3
above, the dihedral angle of
orientation of ~7.9 °. Separately,
4
showed
a near-parallel
(acetonitrile/water, v/v, 1:1) (Figure S33). The fluorescence of
compound was also measured in acetonitrile solvent (Figure
3
and optimized 4/4’ showed
4
~22.1 ° and 16.6 °/30.1 °, not considered as π-π-stacking
(Figure 3). In the case of the rotamer optimized 4’, having the
S34). Other photophysical studies were carried out: e.g.
titrations with various concentrations of NaOCl (Figure S35),
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 6 of 7
View Article Online
DOI: 10.1039/C7DT00555E
ARTICLE
Journal Name
testing of reversibility with glutathione (GSH) (Figure S36), and This work was supported by the (i) Mid-Career Researcher
related time dependent data (Figure S37). Program through the NRF (National Research Foundation) of
To confirm the photomechanism of the ‘turn-on’ Korea (NRF-2014R1A2A1A11052980) funded by MEST, (ii) the
fluorescence by the blocking of the PET process, time- Institute for Basic Science (IBS) and (iii) the High Risk High
dependent density functional theory (TD-DFT) was exploited. Return Program (HRHRP) funded by KAIST. Mr. Youngsam Kim
The largest intense transition in
4 is from the highest occupied and Dr. Sandip V. Mulay acknowledge IBS research
molecular orbital (HOMO) to the lowest unoccupied molecular Fellowships. Ph. D candidate J. Kim under supervision of Prof.
orbital (LUMO) (CI = 87.6 %) with an oscillator strength of ƒ = Dr. W. Y. Kim at KAIST helped with interpretation of the
0.6524, defined here as the dominant transition. DFT/TDDFT calculations. The research support staff at KAIST
Corresponding with fluorescence enhancement, electronic facilitated the acquisition of MS data.
distributions of HOMO and LUMO are exhibited on the BODIPY
core in both
3 and 4. However, in the case of 3, two large
Notes and references
intense transitions were shown. The dominant transition is
from HOMO to LUMO (CI = 77.7 %) with an oscillator strength
of ƒ = 0.2996. The other large intense transition is from HOMO-
1 to LUMO (CI = 79.2 %) and involves an oscillator strength of ƒ
= 0.1007 (Table S3). Concerning the strength of the oscillator
and second largest transition from HOMO-1 to LUMO, these
data assist the assignment of the fluorescence enhancement
as originating from a photo-induced electron transfer (PET)
type mechanism (Figure S38). Moreover, optimized 4/4’
‡ Footnotes relating to the main text should appear here. These
might include comments relevant to but not central to the
matter under discussion, limited experimental and spectral data,
and crystallographic data.
1. (a) C. W. Nogueira, G. Zeni and J. B. T. Rocha, Chem. Rev.,
2004, 104, 6255-6285; (b) G. Mugesh, W.-W. d. Mont and
H. Sies, Chem. Rev., 2001, 101, 2125−2179.
2. (a) J. Młochowski, K. Kloc, R. Lisiak, P. Potaczek and H.
Wójtowicz, ARKIVOC, 2007, 6, 14-46; (b) T. Wirth, Angew.
showed results similar to those for 4: the HOMO to LUMO
Chem. Int. Ed., 2000, 39, 3740-3749; (c) S. Santoro, J. B.
Azeredo, V. Nascimento, L. Sancineto, A. L. Braga and C.
Santi, RSC Adv., 2014, 4, 31521.
transition with largest oscillator strength (CI = 93.7 and 95.3 %,
respectively).
3. (a) H. Sies, Eur. J. Biochem., 1993, 215, 213-219; (b) J.
Saluk-Juszczak, B. Wachowicz, H. Wojtowicz, K. Kloc, E. Bald
and R. Glowacki, Cell. Biol. Toxicol., 2006, 22, 323-329.
4. V. Nascimento, E. E. Alberto, D. W. Tondo, D. Dambrowski,
M. R. Detty, F. Nome and A. L. Braga, J. Am. Chem. Soc.,
2012, 134, 138-141.
Conclusions
We have herein explored novel intramolecular π-π-conjugated
systems in meso-aryl-substituted BODIPY systems. The
oxidation of
3 gives geometrical changes supported by
5. (a) M. Fakih, S. Cao, F. A. Durrani and Y. M. Rustum, Clin.
Colorectal Cancer, 2005, 5, 132-135; (b) Y. Ren, T. Zhao, G.
excellent spectroscopic and spectrometric evidence. The
molecular changes by oxidation showed, not only down-field
shifting, but also splitting of the NMR spectroscopic peaks and
fluorescent enhancement. Hindering the rotation of the meso-
substitution in this study induced intramolecular π-π-
conjugation between the substituted phenyl ring and BODIPY
fluorophore core giving a geometrical change from Cs to C1.
Geometrical changes were confirmed by X-ray crystallography.
Mao, M. Zhang, F. Li, Y. Zou, L. Yang and X. Wu, Int. J. Biol.
Macromol., 2013, 57, 57-62.
6. (a) Z. S. Talas, Y. Gok, I. Ozdemir, B. Ates, S. Gunal and I.
Yilmaz, Pak. J. Pharm. Sci., 2015, 28, 611-616; (b) E. R. T.
Tiekink, Dalton Trans., 2012, 41, 6390-6395.
7. (a) S. T. Manjare, Y. Kim and D. G. Churchill, Acc. Chem.
Res., 2014, 47, 2985-2998; (b) Z. Lou, P. Li and K. Han, Acc.
Chem. Res., 2015, 48, 1358-1368; (c) D. Wu, L. Chen, N.
A comparison of the geometry of
4 with calculated geometry
Kwon and J. Yoon, Chem, 2016,
8. (a) V. Ntziachristos, Annu. Rev. Biomed. Eng., 2006,
(b) A. R. Kherlopian, T. Song, Q. Duan, M. A. Neimark, M. J.
1, 674-698.
optimized versions (optimized 4/4’) also helped confirm the
nature of π-π-stacking between the oxidized PhSe- group and
one side of the BODIPY core. As per our knowledge, this is the
first example clearly showing intramolecular π-π-conjugated
system between a BODIPY fluorophore and its aryl substituent,
as well as any fluorophore / chromophore type group and
phenylchalcogen-substituted group for that matter. Based on
the unexpected optical properties of the selenium compound,
the tellurium analogue was attempted for synthesis. However,
the analogous tellurium-substituted BODIPY was not able to be
synthesized under analogous conditions in our hands. Model
reactions helped better define the debromination for the exact
analogues when Ph2Te2 was used as the reagent.
8, 1–33;
Po, J. K. Gohagan and A. F. Laine, BMC Syst. Biol., 2008, 2,
74-92.
9. (a) G. Ulrich, R. Ziessel and A. Harriman, Angew. Chem. Int.
Ed., 2008, 47, 1184-1201; (b) N. Boens, V. Leen and W.
Dehaen, Chem. Soc. Rev., 2012, 41, 1130-1172; (c) A.
Kamkaew, S. H. Lim, H. B. Lee, L. V. Kiew, L. Y. Chung and K.
Burgess, Chem. Soc. Rev., 2013, 42, 77-88; (d) T. Kowada, H.
Maeda and K. Kikuchi, Chem. Soc. Rev., 2015, 44, 4953-
4972; (e) A. Loudet and K. Burgess, Chem. Rev., 2007, 107
4891-4932; (f) M. M. Ravikanth, L. Vellanki and R. Sharma,
Rep. Org. Chem., 2016, , 1-24; (g) S. P. Singh and T.
,
6
Gayathri, Eur. J. Org. Chem., 2014, 22, 4689-4707.
10. (a) S. Pant, H. B. Tripathi and D. D. Pant, J. Photochem.
Photobiol. A: Chem., 1995, 85, 33-38; (b) M. A. Haidekker,
T. P. Brady, D. Lichlyter and E. A. Theodorakis, Bioorg.
Chem., 2005, 33, 415-425; (c) D. Su, C. L. Teoh, N. Gao, Q.
H. Xu and Y. T. Chang, Sensors, 2016, 16; (d) S. Singha, D.
Acknowledgements
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Dalton Transactions
Page 7 of 7
View Article Online
DOI: 10.1039/C7DT00555E
Journal Name
ARTICLE
Kim, B. Roy, S. Sambasivan, H. Moon, A. S. Rao, J. Y. Kim, T.
Joo, J. W. Park, Y. M. Rhee, T. Wang, K. H. Kim, Y. H. Shin, J.
Suh and D. G. Churchill, Dalton Trans., 2013, 42, 3285–
3290.
Jung and K. H. Ahn, Chem. Sci., 2015,
11. (a) R. Hu, E. Lager, A. Aguilar-Aguilar, J. Liu, J. W. Y. Lam, H.
H. Y. Sung, I. D. Williams, Y. Zhong, K. S. Wong, E. Pena- 19. (a) Y. Kim, M. Choi, S. T. Manjare, S. Jon and D. G. Churchill,
6, 4335-4342.
18. Y. Kim, S. V. Mulay, M. Choi, S. B. Yu, S. Jon and D. G.
Churchill, Chem. Sci., 2015, 6, 5435-5439.
Cabrera and B. Z. Tang, J. Phys. Chem. C 2009, 113, 15845–
15853; (b) N. Dorh, S. Zhu, K. B. Dhungana, R. Pati, F. T.
Luo, H. Liu and A. Tiwari, Sci. Rep., 2015, 5, 18337; (c) S.
Mukherjee and P. Thilagar, Chem. Eur. J., 2014, 20, 9052-
9062; (d) T. T. Vu, M. Dvorko, E. Y. Schmidt, J.-F. Audibert,
RSC Adv., 2016, 6, 32013-32017; (b) B. Wang, F. Yu, P. Li, X.
Sun and K. Han, Dyes and Pigments, 2013, 96, 383-390; (c)
S. V. Mulay, T. Yudhistira, M. Choi, Y. Kim, J. Kim, Y. J. Jang,
S. Jon and D. G. Churchill, Chem. Asian. J., 2016, 11, 3598-
3605.
P. Retailleau, B. A. Trofimov, R. B. Pansu, G. Clavier and R. 20. (a) S. V. Mulay, M. Choi, Y. J. Jang, Y. Kim, S. Jon and D. G.
Méallet-Renault, J. Phys. Chem. C, 2013, 117, 5373-5385;
(e) D. Zhai, W. Xu, L. Zhang and Y. T. Chang, Chem. Soc.
Rev., 2014, 43, 2402-2411.
Churchill, Chem. Eur. J., 2016, 22, 9642-9648; (b) F. Yu, P. Li,
G. Li, G. Zhao, T. Chu and K. Han, J. Am. Chem. Soc., 2011,
133, 11030-11033.
12. (a) S. Burattini, B. W. Greenland, D. H. Merino, W. Weng, J. 21. N. Ghavale, P. P. Phadnis, A. Wadawale, V. K. Jain, Indian J.
Seppala, H. M. Colquhoun, W. Hayes, M. E. Mackay, I. W.
Hamley and S. J. Rowan, J. Am. Chem. Soc., 2010, 132
12051–12058; (b) S. Basak, J. Nanda and A. Banerjee, 22. (a) A. B. Pierini, A. B. Penenory and R. A. Rossi, J. Org.
Chem., Sect. A: Inorg., Bio-inorg., Phys., Theor. Anal. Chem.,
2011, 50, 22-26.
,
Chem. Commun., 2013, 49, 6891-6893; (c) G. B. Demirel, B.
Daglar and M. Bayindir, Chem. Commun., 2013, 49, 6140-
6142; (d) W. E. Lee, Y. J. Jin, S. I. Kim, G. Kwak, J. H. Kim, T.
Chem., 1984, 49, 486-490; (b) A. B. Pierini and R. A. Rossi, J.
Org. Chem., 1979, 44, 4667-4673; (c) Z. Qu, P. Li, X. Zhang
and K. Han, J. Mater. Chem. B, 2016, 4, 887-892.
Sakaguchi and C. L. Lee, Chem. Commun., 2013, 49, 9857- 23. (a) D. C. Dittmer, Q. Li and D. V. Avilov, J. Org. Chem., 2005,
70, 4682-4686; (b) A. A. Vasil’ev and L. Engman, J. Org.
Chem., 1998, 63, 3911-3917.
9859.
13. (a) O. Niyomura, Y. Yamaguchi, S. Tamura, M. Minoura and
Y. Okamoto, Chem. Lett., 2011, 40, 449-451; (b) S. P. Jagtap
and D. M. Collard, J. Am. Chem. Soc., 2010, 132, 12208–
12209; (c) Z. Xu, N. J. Singh, J. Lim, J. Pan, H. N. Kim, S. Park,
K. S. Kim and J. Yoon, J. Am. Chem. Soc., 2009, 131, 15528–
15533; (d) N. S. Kumar, M. D. Gujrati and J. N. Wilson,
Chem. Commun., 2010, 46, 5464-5466; (e) J. Ahn, S. Park, J.
H. Lee, S. H. Jung, S. J. Moon and J. H. Jung, Chem.
Commun., 2013, 49, 2109-2111; (f) C.-B. Huang, L.-J. Chen,
24. T. Chivers and R. S. Laitinen, Chem. Soc. Rev., 2015, 44, 1725-
1739.
J. Huang and L. Xu, RSC Adv., 2014, 4, 19538; (g) Y. Liu, E. J.
Jun, G. Kim, A. R. Lee, J. H. Lee and J. Yoon, Chem.
Commun., 2014, 50, 2505-2507; (h) G. Ding, J. Su, X. Qin, Y.
Lu, L. Ma, H. Li, L. Chen, Z. Luo and F. Gao, Mater. Lett.,
2017, 186, 301-304; (i) Y. Zhang, G. Zhang, R. Zhang, L.
Yang, X. Xu, L. Kong, Y. Tian and J. Yang, Sens. Actuators, B,
2017, 243, 642-649.
14. M. C. Gallazzi, F. Toscano, D. Paganuzzi, C. Bertarelli, A.
Farina, G. Zotti, Macromol. Chem. Phys., 2001, 202, 2074-
2085.
15. J-.A Hong, R. Kim, H-.J. Yun, J-.M. Park, S. C. Shin, Y-.H. Kim,
Bull. Korean Chem. Soc., 2013, 34, 1170-1174.
16. B. A. G. Hammer, F. A. Bokel, R. C. Hayward, T. Emrick,
Chem. Mater., 2011, 23, 4250-4256.
17. (a) S. T. Manjare, J. Kim, Y. Lee and D. G. Churchill, Org.
Lett., 2014, 16, 520-523; (b) S. T. Manjare, S. Kim, W. D.
Heo and D. G. Churchill, Org. Lett., 2014, 16, 410-412; (c) B.
Wang, P. Li, F. Yu, P. Song, X. Sun, S. Yang, Z. Lou and K.
Han, Chem. Commun., 2013, 49, 1014-1016; (d) S.-R. Liu
and S.-P. Wu, Org. Lett., 2013, 15, 878-811; (e) K. Kim, C.
Jo, S. Easwaramoorthi, J. Sung, D. H. Kim and D. G.
Churchill, Inorg. Chem., 2010, 49, 4881-4894; (f) A. P. Singh,
K. M. Lee, D. P. Murale, T. Jun, H. Liew, Y. H. Suh and D. G.
Churchill, Chem. Commun., 2012, 48, 7298-7300; (g) S. H.
Choi, K. Pang, K. Kim and D. G. Churchill, Inorg. Chem.,
2007, 46, 10564-10577; (h) S. H. Choi, K. Kim, J. Jeon, B.
Meka, D. Bucella, K. Pang, S. Khatua, J. Lee and D. G.
Churchill, Inorg. Chem., 2008, 47, 11071-11083; (i) A. P.
Singh, D. P. Murale, Y. Ha, H. Liew, K. M. Lee, A. Segev, Y.-H.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins