Difluoroboron β-diketonate dye with intense red/near-infrared fluorescence in solutions and solid states

Article abstract of DOI:10.1016/j.cclet.2019.04.058

Difluoroboron β-diketonate (BF₂bdk) complexes have attracted much attention due to their outstanding photophysical properties. However, BF₂bdk with near-infrared fluorescence usually suffer from emission quenching in solid state due to the π–π stacking in aggregation. Herein, we report a BF₂bdk dye exhibiting donor-acceptor (D-A) structure with the difluoroboron moiety acting as the electron acceptor and the aminonaphthalene as the electron donor. It processes intense molar extinction coefficient, large Stokes shift and strong fluorescence in red/NIR region in both solution and aggregations. It was used for NIR imaging in living cells.

Full text of DOI:10.1016/j.cclet.2019.04.058

Accepted Manuscript
Title: Difluoroboron β-diketonate dye with intense
red/near-infrared fluorescence in solutions and solid states
Authors: Nan Liu, Peng-Zhong Chen, Jian-Xin Wang, Li-Ya
Niu, Qing-Zheng Yang
PII:
DOI:
Reference:
S1001-8417(19)30232-3
https://doi.org/10.1016/j.cclet.2019.04.058
CCLET 4951
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
26 March 2019
9 April 2019
22 April 2019
Please cite this article as: Liu N, Chen P-Zhong, Wang J-Xin, Niu L-Ya,
Yang Q-Zheng, Difluoroboron β-diketonate dye with intense red/near-infrared
fluorescence in solutions and solid states, Chinese Chemical Letters (2019),
https://doi.org/10.1016/j.cclet.2019.04.058
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.

Communication
Difluoroboron β-diketonate dye with intense red/near-infrared fluorescence in
solutions and solid states
Nan Liu, Peng-Zhong Chen, Jian-Xin Wang, Li-Ya Niu, Qing-Zheng Yang
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China
 Corresponding author.
E-mail address: niuly@bnu.edu.cn
Graphical Abstract
We reported a difluoroboron β-diketonate dye that displays bright red/NIR fluorescence in both solutions and solid states.
ARTICLE INFO
ABSTRACT
Article history:
Difluoroboron β-diketonate (BF2bdk) complexes have attracted much attention due to their
outstanding photophysical properties. However, BF2bdk with near-infrared fluorescence usually
suffer from emission quenching in solid state due to the π–π stacking in aggregation. Herein, we
report a series of BF2bdk dye exhibiting donor-acceptor (D-A) structure with the difluoroboron
moiety acting as the electron acceptor and the aminonaphthalene as the electron donor. It
processes intense molar extinction coefficient, large Stokes shift and strong fluorescence in
red/NIR region in both solution and aggregations. It was used for NIR imaging in living cells.
Received 26 March 2019
Received in revised form 10 April 2019
Accepted 16 April 2019
Available online
Keywords:
Difluoroboron β-diketonate
Near-infrared
Solid state emission
Bioimaging
Difluoroboron β-diketonate (BF2bdk) complexes have
attracted much attention in recent years due to their impressive
properties [1-17], such as strong fluorescence in both solution
and solid state, large molar absorption coefficients, two-photon
excited fluorescence, mechanochromic luminescence and room
[18, 19], organic light-emitting diodes (OLED) [20-22], and
photodynamic therapy [23, 24].
The photoluminescence properties of BF2bdks strongly depend
on the nature of their substitutions at 4, 6-positions of
dioxaborine ring. In general, BF2bdks with aliphatic groups at
both 4, 6-positions are nonfluorescent in visible region due to the
limited molecular conjugation, while BF2bdks bearing aryl
groups at 4, 6-positions are usually emissive and show tunable
emission spectra from visible to near infrared (NIR) region by
temperature
phosphorescence.
Hence,
their
attractive
performances have made them a research focus and these
attributes make them have wide applications in various fields,
including fluorescent and phosphorescence imaging and sensing
———
 Corresponding author.
E-mail address: niuly@bnu.edu.cn

modulation of structural properties of ligands. In particular, NIR
emission (650–900 nm) has distinct advantages in bioimaging
and biosensing [25-27], including low photodamage to biological
samples, deep tissue penetration, and minimum interference from
background autofluorescence in living biosystems. Accordingly,
the development of BF2bdk-based NIR fluorophore is highly
desirable and valuable for bioapplications. However, among the
most of the reported BF2bdk complexes, there are only a few
reports on the properties and applications of BF2bdk complexes
with intense red/near-infrared fluorescence. D’Ale´o et al. have
developed a series of curcuminoid and hemicurcuminoid based
BF2bdk derivatives whose emission red-shifted to red/near-
infrared region [28, 29]. However, such structures usually suffer
from emission quenching in solid state due to the π–π stacking in
aggregation. Herein, we report a BF2bdk derivative N1 that
display bright NIR fluorescence in both solution and solid state.
By linking naphthalene to the 6-position of dioxaborine ring,
BF2bdk complex displays a considerable degree of aromaticity
and expands the π-conjugation, leading the absorption/emission
wavelength to red shift. Introduction of electron-donating amino
groups to the naphthalene ring further shifts their absorption and
emission due to the intramolecular charge transfer (ICT) from the
ligands to the electron deficient dioxaborine ring. On the other
hand, upon modulation of electron-donating or -withdrawing
substituents of the aromatic rings on the 4-position, we
synthesized compound N1-N4 and studied their optical
properties in organic solvents and solid states.
Scheme 2. Synthesis of N1-N4.
The complexes N1–N4 are typical donor–acceptor (D-A) type
fluorophores, with the difluoroboron moiety acting as the
electron acceptor and the aminonaphthalene as the electron donor.
The UV-vis absorption spectra for dyes N1–N4 in different
solvents are shown in Fig. S1 in Supporting information. All the
spectra display relatively small absorption bands at λmax < 400
nm, which are assigned to the π–π* transitions. The strong
absorption bands ranging from λmax = 455-559 nm has large
molar extinction coefficient (ε > 5×104 L mol-1 cm-1). Such large
ε, associated with the bathochromic shift of the lowest-energy
transition band with the polarity of the solvent, is characteristic
of an ICT. This process is confirmed by the equilibrium
geometries of ground (Sn) state of N1-N4 in gas phase which
determined at B3LYP/6-31G level using DFT method (Fig. 1 and
Fig. S2 in Supporting information). In all complexes, the HOMO
and LUMO are mainly localized on aminonaphthalene and the
dioxaborine ring, respectively, indicating ICT transition from the
electron-donating aminonaphthalene units to electron-accepting
dioxaborine ring. In addition, the longest absorption maxima are
related to the electron-donating/withdrawing ability of the
ligands. The absorption maxima of N1-N3 with aryl groups show
red-shift compared to N4 in the same type solvent due to the
expanded π-conjugation. The most red-shifted spectrum is
obtained from the cyano analogues.
Scheme 1. Chemical structures of BF2bdks N1-N4.
The synthetic routes of BF2 complexes N1–N4 are illustrated
in Scheme 2. Firstly, the 6-amino-2-naphthoic acid methyl ester
reacted with the methyl iodide to obtain N, N′-dimethyl groups.
Then, the ketone precursors were deprotonated by NaH before
reacting with the desired esters via the Claisen condensation
reaction according to the literature. Finally, the BF2 complexes
N1–N4 were easily prepared from the β-diketonate ligands LN1–
LN4 and BF3/Et2O in CH2Cl2. The target compounds N1–N4
1
were characterized by H NMR, 13C NMR spectroscopy, high
resolution mass spectrometry analysis.
Fig. 1. Spatial distributions of the calculated HOMO and LUMO of
N1. Calculations are based on ground state geometry by DFT at the
B3LYP/6-31G* level.
The emission spectra of BF2bdk complexes N1–N4 in different
solvents are provided in Fig. 2. All the chromophores display
marked positive solvatochromism of their emission. The
considerable bathochromic shifts in a polar solvent indicates
enlarged dipoles and charge-transfer characteristics in their
excited states. For instance, the overall emission bathochromic

shifts of N1 is 143 nm from low-polarity toluene to high-polarity
dimethyl sulfoxide (DMSO) (Table 1). Besides, the emission
quantum efficiency also shows a strong dependence on the
solvent’s polarity (Table S1 in Supporting information). N1-N4
display strong fluorescence with quantum yields > 90% in
nonpolar or less polar solvents. For example, the QY of N1 in
toluene is close to unity (~95%). Upon increasing the solvent
polarity, a marked decrease in the luminescence efficiency is
observed, because ICT state is known to be able to go through
nonradiative deactivation in polar solvents. The emission
maxima of N1-N3 are red shifted compared to the compound N4
in the CH2Cl2, due to the larger π-conjugation systems. The
introduction of different functional groups on the para position
of phenyl ring has a significant effect on the emission properties
of BF2 complexes. The emission maxima of N1, N2 and N3 is
555, 573 and 582 nm in toluene. N1 possesses ICT process in
two directions (D-A-D type), which weakens the whole ICT
process and is the possible reason for the blue-shifted emission.
Compound N3 with the largest D-A conjugation system displays
the most red-shifted emission.
Fig. 3. Emission spectrum of N1 in solid state. Inset: photograph of
N1 powder under UV lamp at 365 nm.
The emission properties of the chromophores N1-N4 in the
solid state are also investigated (Table S2 in Supporting
information). The emission of the four complexes in solid state
are located at 690-780 nm in the near-infrared region,
significantly red-shifted compared to those in DCM solution,
indicating strong intermolecular interactions between
chromophores in solid state. Moreover, compound N1 in solid
state possesses the highest fluorescence quantum yield of 13%
(Φf = 0.13). We assumes that a twist conformation would hamper
the tight π–π stacking between the molecules in solid state.
In aqueous media, intrinsic hydrophobicity of aromatic
structures of fluorophores will cause the formation of
nanoaggregates. The bright fluorescence of N1 in aggregates is a
very attractive feature for applications in biological imaging. In
addition, compound N1 with large Stokes shift is of great
advantage to avoid the interference from excitation and scattered
light [30]. We examine the fluorescence imaging performance of
N1 in HeLa cells by using confocal laser scanning microscopy
(CLSM). As shown in Fig. 4, after incubation with N1 for 30 min,
emission NIR channels are observed throughout the cytoplasmic
area of the HeLa cells. The result indicates the NIR dye N1 is
able to be applied for NIR bioimaging.
Fig. 2. Normalized fluorescence spectra of (a) N1, (b) N2, (c) N3
and (d) N4 in different solvents (1 × 10−5 mol/L).
Table 1
Photophysical data of N1 in different solvents.
a
c
e
f
Solvents
λabs
ε b
λem
Δν d
Φf
τf
(nm) (L mol-1 cm-1)
(nm) (cm−1)
(ns)
Fig. 4. CLSM images of HeLa cells incubated with N1. (a) NIR
channel. (b) Bright field channel. (c) Overlay of (a) and (b).
Toluene
DCM
Chloroform 494
484
499
53400
55800
58800
60600
57900
41100
54600
555
631
596
618
660
681
698
2643
4192
3464
4395
5174
5477
5205
0.95
0.62
0.99
0.52
0.12
0.01
2.96
2.71
3.54
2.68
0.72
0.42
In conclusion, we developed a new class of BF2bdk-based
dyes containing aminonaphthalene units with intense red/near-
infrared fluorescence. They showed red-shifted absorption and
emission spectra by introducing electron-withdrawing groups as
the other ligand. Particularly, N1 exhibited strong emission with
quantum yield of 0.13 in solid state. It was successfully applied
for NIR imaging in living cells. Possessing intense molar
THF
486
492
496
512
Acetone
MeCN
DMSO
a Absorption maxima.
0.007 0.54
b Extinction coefficients calculated at the absorption maxima.
c Fluorescence emission maxima.
d Stoke shifts, Δν, were calculated using the equation 1/λabs-1/λem
e The absolute fluorescence quantum yields.
.
extinction
coefficient,
large
Stokes
shift,
positive
f Fluorescence lifetimes were measured with a EPLEDs (picosecond
pulsed LEDs) light source and monitored at the emission maximum.
All fluorescence lifetimes were fitted with single-exponential decays
unless indicated.
solvatochromism in different solvents and strong fluorescence in
NIR region in aggregations, N1 holds potential application as an
environment sensitive probe in living systems.
Acknowledgment

[15] T. Butler, M. Zhuang, C.L. Fraser, J. Phys.Chem. C 122 (2018)
19090-19099.
[16] G.R. Krishna, M.S.R.N. Kiran, C.L. Fraser, U. Ramamurty,
C.M. Reddy, Adv. Funct. Mater. 23 (2013) 1422-1430.
[17] G. Zhang, J. Chen, S.J. Payne, et al., J. Am. Chem. Soc. 129
(2007) 8942-8943.
This work was financially supported by National Natural
Science Foundation of China (No. 21525206).
References
[18] P. Zhang, Z.Q. Guo, C.X. Yan, W.H. Zhu, Chin. Chem. Lett. 28
(2017) 1952-1956.
[19] R.F. Wang, H.Q. Peng, P.Z. Chen, et al., Adv. Funct. Mater. 26
(2016) 5419-5425.
[20] Q. Liao, X.G. Wang, S. Lv, et al., ACS Nano 12 (2018) 5359-
5367.
[21] C.T. Poon, D. Wu, V.W.W. Yam, Angew. Chem. Int. Ed. 55
(2016) 3647-3651.
[22] H.W. Mo, Y. Tsuchiya, Y. Geng, et al., Adv. Funct. Mater. 26
(2016) 6703-6710.
[23] B. Bai, C. Yan, Y. Zhang, Z. Guo, W.H. Zhu, Chem. Commun.
54 (2018) 12393-12396.
[24] K.S. Park, M.K. Kim, Y. Seo, et al., ACS Chem. Neurosci. 8
(2017) 2124-2131.
[25] W. Chen, Y. Pan, J. Chen, et al., Chin. Chem. Lett. 29 (2018)
1429-1435.
[26] P.Z. Chen, H.R. Zheng, L.Y. Niu, et al., Chin. Chem. Lett. 26
(2015) 631-635.
[27] Z. Guo, S. Park, J. Yoon, I. Shin, Chem. Soc. Rev. 43 (2014)
16-29.
[28] P.H. Lanoë, B. Mettra, Y.Y. Liao, et al., ChemPhysChem 17
(2016) 2128-2136.
[29] A. Felouat, A. D’Aléo, F. Fages, J. Org.Chem 78 (2013) 4446-
4455.
[1] P.Z. Chen, L.Y. Niu, Y.Z. Chen, Q.Z. Yang, Coord. Chem. Rev.
350 (2017) 196-216.
[2] D.H. Kim, A. D’Aléo, X.K. Chen, et al., Nat. Photonics 12
(2018) 98-104.
[3] X.F. Wang, H. Xiao, P.Z. Chen, et al., J. Am. Chem. Soc. (2019)
DOI: 10.1021/jacs.9b00859
[4] G. Zhang, G.M. Palmer, M.W. Dewhirst, C.L. Fraser, Nat.
Mater. 8 (2009) 747.
[5] W. Huang, X. Zhang, B. Chen, et al., Chem. Commun. 55 (2019)
67-70.
[6] Q. Jiang, M. Zhang, Z. Wang, et al., RSC Adv. 8 (2018) 30055-
30060.
[7] L. Wilbraham, M. Louis, D. Alberga, et al., Adv. Mater. 30
(2018) 1800817.
[8] P.Z. Chen, H. Zhang, L.Y. Niu, et al., Adv. Funct. Mater. 27
(2017) 1700332.
[9] T. Liu, G. Zhang, R.E. Evans, et al., Chem.-Eur. J. 24 (2018)
1859-1869.
[10] P.Z. Chen, L.Y. Niu, H. Zhang, Y.Z. Chen, Q.Z. Yang, Mater.
Chem. Front. 2 (2018) 1323-1327.
[11] P.Z. Chen, Y.X. Weng, L.Y. Niu, et al., Angew. Chem. Int. Ed.
55 (2016) 2759-2763.
[12] P.Z. Chen, J.X. Wang, L.Y. Niu, Y.Z. Chen, Q.Z. Yang, J.
Mater. Chem. C 5 (2017) 12538-12546.
[30] T.B. Ren, W. Xu, W. Zhang, et al., J. Am. Chem. Soc. 140
(2018) 7716-7722.
[13] K. Kamada, T. Namikawa, S. Senatore, Cet al., Chem.-Eur. J.
22 (2016) 5219-5232.
[14] M. Louis, R. Sethy, J. Kumar, et al., Chem. Sci. 10 (2019) 843-
847.