H+-Assisted fluorescent differentiation of Cu+ and Cu2+: Effect of Al3+-induced acidity on chemical sensing and generation of two novel and independent logic gating pathways

Article abstract of DOI:10.1039/c4cc10025e

A novel Schiff base probe exhibited strong 'turn-ON' fluorescence for Cu²⁺ at 345 nm, Al³⁺ at 445 nm, and Cu⁺ at 360 nm in the presence of Al³⁺ in organic solvent (acetonitrile), which allowed for construction of molecular logic gates 'INH' and '1:2 DEMULTIPLEXING.' H⁺ generated from Al³⁺ contributed greatly to Cu⁺ chemosensing based on a redox non-innocence mechanism.

Full text of DOI:10.1039/c4cc10025e

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DOI: 10.1039/C4CC10025E
Journal Name
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H+–Assisted Fluorescent Differentiation of Cu+ and
Cu2+: Effect of Al3+–induced acidity on chemical
sensing and generation of two novel and independent
logic gating pathways
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
Yonghwang Haa, Dhiraj P. Muralea, Changsuk Yuna, Sudesh T. Manjarea,b, Hyungjun
Kima, Juhyoun Kwaka, Yoon Sup Leea, David G. Churchilla,*
DOI: 10.1039/x0xx00000x
www.rsc.org/
16, 17
fluorescence intensity.1,
Therefore, H+, induced by Al3+, can be
A novel Schiff base probe exhibited strong ‘turn–ON’
fluorescence for Cu2+ at 345 nm, Al3+ at 445 nm, and Cu+ at
360 nm in the presence of Al3+ in organic solvent
(acetonitrile), which allowed for construction of molecular
considered in molecular fluorescence probe design.
logic gates ‘INH’ and
‘1:2 DEMULTIPLEXING.’
H+
generated from Al3+ highly contributed to Cu+ chemosensing
based on a redox non-innocence mechanism.
Preparation of novel synthetic systems to exploit the behavior
of Cu+/2+, especially in terms of photophysical changes, has become a
very important issue for the diagnosis of disease progression. One of the
best strategies for probing metal ions is fluorescence chemosensing; the
sensitivity, selectivity and ease of operation are all possible. In particular,
however, the differentiation by fluorescence of Cu+ and Cu2+ is
challenging.1 Moreover, Cu2+ often imparts a quenching effect on
molecular fluorescence because of its paramagnetic ability. Also, Cu+
(aq)
Scheme 1. Fluorescence “turnꢀON” probing for Cu+, Cu2+, and Al3+ with
Comp. 2.
can be degraded via disproportionation into Cu0 and Cu2+(aq). Certain
1ꢀ5
chemical probes have been developed for the detection of Cu+
and
Cu2+ by fluorescent “Turn–ON” sensing.6ꢀ10 Some strategies in these
studies for Cu+ sensing have involved the adaptation of NS3 or NS4
Herein, a selective probe for Al3+, Cu+ and Cu2+ via chelation–
enhanced fluorescence (Scheme 1), involves the salicylaldamine with an
N–dimethyl carbamoyl group, a straight–forward and simple protection
of the phenol group which has been unexplored in chemosensing
(Scheme 2).18, 19 Analytical measurements were undertaken to elucidate
sensitivity, selectivity, reversibility, binding analysis using fluorescence,
UVꢀvis absorbance, 1HꢀNMR, and EPR analysis.
When 16 kinds of metal ions were screened with fluorescence,
strong fluorescence ‘OFF – ON’ signals were found for two metal ions
in entirely separate regions of the spectrum: for Cu2+ at λem–max = 352 nm
(85–fold), and Al3+ at λem–max = 445 nm (771–fold), relative to the starting
intensity of 2 (Figure 1(a)). These two ‘turn–ON’ signals in different
wavelength zones allow for very minimal spectral overlap with each
other, implying this probe can analyze either Cu2+ or Al3+ ions, or
potentially both by fluorescence in solution.
2, 5
3
coordination environments (cyclic or acyclic thioaza groups which
include nitrogen and sulfur donor atoms) or reaction–based sensing.4 For
the probing of Cu2+, chelation strategy using species that include Schiff
bases 6ꢀ8, 10 or reaction–based probing9 have been used.
Meanwhile, aluminum (Al3+) is an important analyte in that it
can leach into the environment and induce various toxic effects on
human health. i.e., numerous claims have been made in the past
literature involving how Al3+ could be linked to neurodegenerative
disease incidence such as Alzheimer’s disease.11 In fact, the hydronium
ion can be generated when Al3+ is dissolved in water. Unwanted effects
12ꢀ15
of the hydronium ion as a by–product of Al3+ aqueous solvation
on
chemical sensing has been little discussed. Nitrogen atoms in secondary
or tertiary amine groups of molecular probes can provide binding sites
for protonation during chemical sensing. H+, attached to e.g.,
amine/imine groups, can influence e.g., the photoinduced electron
transfer (PET) mechanism of a probe molecule which usually decreases
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Binding sites of 2 with metal ions and H+ were examined
16
N
O
15
H2N
NH2
14
3
using H NMR analysis (Figure 3, ESI, Figure S13–S14). For the Cu+ꢀ
only case, a strong broadening effect on the urea NH (H3) and imine
protons (H5), aromatic protons (H7–10) and carbamoyl methyl protons
(H16–17) was shown, implying that Cu+ changed into Cu0 and Cu2+ to give
a strong paramagnetic effect on the protons of the overall ligand (Figure
1
O
O
O
N
N
N
N
17
10
H
H
13
O
N
1
O
12
O
5
O
9
11
4
N
EtOH / H2O = 1:1
140 oC, Reflux, 24 h
O
8
2
2
6
N
N
H
H
7
1
1
3). However, Cu+ with Al3+ showed a different H NMR spectral pattern
Scheme 2. Synthesis of the fluorescence probe (Comp. 2).
from the case of Cu+ only, not total broadening of 1H NMR peaks. Comp.
2 with Al3+ and Cu+ exhibited partial broadening of the urea NH, imine
hydrogen and aromatic hydrogens, excluding those for the carbamoyl
group. In particular, the signal from the imine hydrogen signal (H5) was
too broad to be observed clearly indicated by the red arrow (Figure 3).
This implies that the preference of Cu+ is to partially, but strongly,
interact with the specific area (urea, imine, and aromatic region) of the
ligand, distal to the carbamoyl group, and the binding mode of Cu+ with
Al3+ is markedly different from that for Cu+ only.
Interestingly, Cu+ displayed a new emission intensity of 360
nm (32–fold), similar to Cu2+ (low concentration) (Figure 1(b) in the
presence of Al3+, whereas Cu+ itself did not show an emission signal. It
is important to verify the influence of H+ generated by Al3+ on Cu+–
induced fluorescence in the presence of Al3+. As shown in ESI, Figure
S11, while only a small fluorescence increase was shown at ~445 nm in
the presence of H+ only, co–incubation of Cu+ (10 equiv) and H+ (10
equiv) displayed strong fluorescence at the same wavelength of Al3+ and
Cu+ co–treated solution, which strongly suggest H+, generated by Al3+,
takes an important role for Cu+ fluorescence “turn-ON”.
Figure 2. EPR spectral analysis of 2 with Cu+, Cu2+ and Al3+.
Concentrations: Cu2+ (400 ꢁM), 2 (200 ꢁM) + Cu2+ (400 ꢁM), 2 (200
ꢁM) + Al3+ (200 ꢁM) + Cu+ (200 ꢁM), Solvent; acetonitrile mixed with
2 % (v/v) DMSO.
(a)
(b)
Figure 1. Emission spectrum of Comp. 2 (10 µM, 1 equiv) with Ag+,
Al3+, Ca2+, Cd2+, Co2+, Cu+, Cu2+, Fe2+, Fe3+, Hg2+, K+, Mg2+, Mn2+, Na+,
Pb2+, Zn2+ ions (100 µM, 10 equiv). (b) Interference experiments of
Comp. 2 with Al3+ against other metal ions. λex = 300 nm, Slit width
(EM: 5 nm, EX: 5 nm). Solvent: acetonitrile.
1
Figure 3. H NMR analysis of 2 (1 equiv) with Al3+ (1 equiv), Cu+ (1
equiv), or Al3+ (1 equiv) + Cu+ (1 equiv) for verifying interaction sites at
9.2 ppm – 6.9 ppm. Solvent: DMSO–d6 + D2O (4.3 v/v %).
Fluorescence mechanism in this probing system elicits three
points of discussion. (i) Cu+ fluorescence signal in the presence of Al3+
showed the same emission wavelength as that for Cu2+ (Figure 1). (ii) H+
generated by Al3+ in aqueous solution contributed greatly to Cu+
fluorescence (ESI, Figure S11). (iii) Although 2 does not possess soft
donor atoms ideal for binding Cu+, Cu+ binding with 2 in the presence of
Al3+ was bound strong and stable enough so that Cu+ cannot be
substituted with Cu2+ or Al3+ or disproportionation as seen through the
interference, titration experiments, and EPR analysis (Figure 1ꢀ2, ESI,
Figure S5, S10).
In accord with copper Fenton–type chemistry between Cu2+
and Cu+, spin multiplicity was investigated for Cu+, Cu2+ and Al3+ in
relationship with 2 by EPR spectroscopic analysis. In Figure 2, Cu2+
showed a characteristic EPR spectroscopic signal.20 Comp. 2 with Cu2+
did not shift the signal relative to that for Cu2+ only, implying
coordination of Cu2+ with 2 suggesting weak binding. Interestingly, the
EPR spectrum after 40 min incubation of 2 with Cu+/Al3+ was silent,
suggesting Cu+·2 binding did not allow for disproportionation to
paramagnetic Cu2+; or perhaps a minute amount of Cu+ was changed into
Cu2+, an amount below detection by EPR spectroscopy.
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DOI: 1C0.O10M39M/CU4CNCI1C0A0T25IOE N
To rationalize these phenomena,
a
redox non–innocence
As shown in Scheme 3 and in the ESI. (Figure S9ꢀ10) Crucial
mechanism can be proposed (ESI, Figure S20). Redox non–innocence has fluorescence signal changes were observed under various conditions of
been reported in many studies,21-25 and deals with stabilizing the Comp. 2, Cu2+, Al3+, Cu+, and Lꢀcysteine. From the result for Comp. 2,
coordination between transition metal ions and ligands and electron with Cu2+ and Lꢀcysteine, were able to allow for the construction of an
transfer between the transition metal ions and the ligand without a spin ‘INH’ molecular logic gate (Scheme 3 (left)). In addition, as shown in
multiplicity change, which induces higher or lower oxidation states of the Figure S10, the two output signals at 345 nm and 445 nm were observed
transition metal ion to induce a more stable interaction. Through the UV– in the presence of Al3+, Cu+, and Comp. 2, which were arranged to
visible absorbance results for 2 with Cu+ and Al3+, a new long wavelength signify a 1:2 DEMULTIPLEXING’ logic gate (Scheme 3 (right)).29
peak at 460 nm (ESI, Figure S8(c)) was revealed, evident of a redox non–
innocent system.26, 27 This redox non–innocence allows us to explain three
previous points of discussion. Cu+ gives one electron to the ligand and
changes into Cu2+ without a spin multiplicity change based on EPR
spectroscopic results. Cu2+, in a higher oxidation state than Cu+, can bind
strongly with the ligand; although this probe has no softer elements like
sulfur, from interference results and titration results (ESI, Figure S5, S10),
this shows the same emission maximum wavelength, similar to the result
for Cu2+ alone. For electron transfer, a positive species like H+ appears to
take on an important role to decrease the activation energy of electron
(negative charge) transfer from Cu+ to the ligand.28 Consequently, the
transferred single electron is distributed around the entire ligand except for
Scheme 3. Construction of molecular logic gates for Cu2+, Al3+, Cu+ and
Lꢀcysteine. (left) ‘INH’ logic gate for Cu2+ and Lꢀcysteine, (right) ‘1:2
DEMULTIPLEXING’ logic gate from Al3+ and Cu+.
1
the carbamoyl group, which explains the partial broadening effect on Hꢀ
NMR signal at urea NH, imine hydrogen and aromatic hydrogens. In
particular, for H+ binding in the ligand, the imine nitrogen (N4) is the most
adequate because of its strong basicity. Therefore, an electron transferred
from Cu+ can remain for a relatively long time in the protonated imine area,
which induces a strongly broadening effect observed in the 1HꢀNMR signal
of the imine proton (H5) in Figure 3 (red arrow).
Prof. David G. Churchill (D. G. C.) acknowledges support
from the NRF (National Research Foundation) of Korea (2011–0017280,
NRFꢀ2014R1A2A1A11052980), and the EndꢀRun Project of KAIST
(N01140684). Sudesh T. Manjare acknowledges the support from
Institute of Basic Science (IBS). EPR analysis were performed through
the support of the Korea Basic Science Institute (KBSI, Daejeon). Prof.
Yoon Sup Lee acknowledges NRF grant # (2007–0056095) and
computational resources from KISTI (KSC–2012–C2–41). YH
acknowledges comments from Prof. Dongwhan, Lee at Dept. of
Chemistry, Seoul National University, and Prof. Mu–Hyun, Baik at Dept.
of Chemistry, Indiana University.
Electrochemical experiments are performed to clarify
oxidation state of copper in metal complex (Figure 4). The blue line
represents electrochemical properties of 2 mM Cu+ in 0.1 M TBAP in
DMSO. Cu+ shows cathodic (Epc) and anodic (Epa) peak potentials at ꢀ
0.65 and ꢀ0.57 V vs Fc+/Fc, respectively (E0' = ꢀ0.62 V vs Fc+/Fc,
approximately). However, when copper(I) was present with the
protonated ligand, additional redox peaks appeared (red line), strongly
suggesting metal ligand complexation, Epa1, Epc1, Epa2, and Epc2 at ꢀ0.03, ꢀ
0.30, ꢀ0.35 and ꢀ0.50 V vs Fc+/Fc, respectively. This reveals that there
Notes and references
a
Department of Chemistry, Korea Advanced Institute of Science and
0'
are two redox reaction steps in the metal complex: E1 = ꢀ0.17 V vs
Technology (KAIST), 373–1 Guseong–dong, Yuseong–gu, Daejeon,
0'
Fc+/Fc and E2 = ꢀ0.43 V vs Fc+/Fc for each step. Although Figure S21
305–701, Republic of Korea.
shows that ligand is not electroactive, when Cu+ is combined with
protonated ligand, Cu+ donates one electron to the ligand and changes
oxidation state from copper(I) to copper(II). As a result, we conclude
that there exist “redox nonꢀinnocent” characteristics of the ligand that
affect the oxidation state of the metal.
b Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic
Science (IBS), 373−1 Guseong−dong, Yuseong−gu, Daejeon, 305−701,
Republic of Korea.
† The present affiliations of DPM (postdoctoral fellow) and STM
(assistant professor) are Korea Institute of Science and Technology
(KIST), Seoul, Republic of Korea, and Dept. of Chemistry, University of
Mumbai, India, respectively.
6e-6
4e-6
2e-6
0
†
Synthesis of the probe, NMR data (1H, 13C), DFT results, Job
plotting results, titration results, reversibility data by biothiols, and
experiments about the probing reliability of Cu+ in this system can be
seen
in
electronic
supporting
information
(
ESI):
See
-2e-6
-4e-6
DOI: 10.1039/c000000x/
1.
2.
C. J. Fahrni, Curr. Opin. Chem. Biol., 2013, 17, 656ꢀ662.
M. T. Morgan, P. Bagchi and C. J. Fahrni, J. Am. Chem. Soc.,
2011, 133, 15906ꢀ15909.
0.1 M TBAP in DMSO
Metal complex(2 mM Cu+, 1 mM Ligand, 10 mM H+)
2 mM Cu+
-6e-6
-0.8
-0.6
-0.4
-0.2
0.0
0.2
0.4
3.
4.
5.
X. W. Cao, W. Y. Lin and W. Wan, Chem. Commun., 2012, 48,
6247ꢀ6249.
M. Taki, S. Iyoshi, A. Ojida, I. Hamachi and Y. Yamamoto, J.
Am. Chem. Soc., 2010, 132, 5938ꢀ+.
A. F. Chaudhry, S. Mandal, K. I. Hardcastle and C. J. Fahrni,
Chem. Sci., 2011, 2, 1016ꢀ1024.
Potential(V vs Fc+/Fc)
Figure 4. Cyclic voltammetry of Comp. 2 with Cu+ and H+.
This journal is © The Royal Society of Chemistry 2012
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VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4CC10025E
6.
7.
Y. Zhou, F. Wang, Y. Kim, S. J. Kim and J. Yoon, Org. Lett.,
2009, 11, 4442ꢀ4445.
O. GarciaꢀBeltran, N. Mena, L. C. Friedrich, J. C. NettoꢀFerreira,
V. Vargas, F. H. Quina, M. T. Nunez and B. K. Cassels,
Tetrahedron Lett., 2012, 53, 5280ꢀ5283.
8.
H. C. Lan, B. Liu, G. L. Lv, Z. H. Li, X. D. Yu, K. Y. Liu, X. H.
Cao, H. Yang, S. P. Yang and T. Yi, Sens. Actuators, B, 2013,
173, 811ꢀ816.
9.
J. X. Yin, X. Ma, G. H. Wei, D. B. Wei and Y. G. Du, Sens.
Actuators, B, 2013, 177, 213ꢀ217.
10.
S. Khatua, S. H. Choi, J. Lee, J. O. Huh, Y. Do and D. G.
Churchill, Inorg. Chem., 2009, 48, 1799ꢀ+.
11.
12.
K. P. Kepp, Chem. Rev., 2012, 112, 5193ꢀ5239.
W. H. Ding, C. Wei, X. J. Zheng, D. C. Fang, W. T. Wong and L.
P. Jin, Inorg. Chem., 2013, 52, 7320ꢀ7322.
13.
14.
Y. G. Zhao, Z. H. Lin, H. P. Liao, C. Y. Duan and Q. J. Meng,
Inorg. Chem. Commun., 2006, 9, 966ꢀ968.
M. Arduini, F. Felluga, F. Mancin, P. Rossi, P. Tecilla, U.
Tonellato and N. Valentinuzzib, Chem. Commun., 2003, 1606ꢀ
1607.
15.
16.
17.
18.
19.
20.
H. M. Park, B. N. Oh, J. H. Kim, W. Qiong, I. H. Hwang, K. D.
Jung, C. Kim and J. Kim, Tetrahedron Lett., 2011, 52, 5581ꢀ5584.
L. Zeng, E. W. Miller, A. Pralle, E. Y. Isacoff and C. J. Chang, J.
Am. Chem. Soc., 2005, 128, 10ꢀ11.
M. T. Morgan, P. Bagchi and C. J. Fahrni, Dalton Trans., 2013,
42, 3240ꢀ3248.
A. Velavan, S. Sumathi and K. K. Balasubramanian, Eur. J. Org.
Chem., 2013, 3148ꢀ3157.
A. Ohkubo, R. Kasuya, K. Miyata, H. Tsunoda, K. Seio and M.
Sekine, Org. Biomol. Chem., 2009, 7, 687ꢀ694.
Y. Ha, A. Yang, S. Lee, K. Kim, H. Liew, S. H. Lee, J. E. Lee, H.
I. Lee, Y. H. Suh, H. S. Park and D. G. Churchill, J. Neurosci.
Res., 2014, 92, 359ꢀ368.
21.
22.
23.
24.
25.
26.
V. Lyaskovskyy and B. de Bruin, ACS Catalysis, 2012, 2, 270ꢀ
279.
I. S. Ke, J. S. Jones and F. P. Gabbai, Angew. Chem. Int. Ed.,
2014, 53, 2633ꢀ2637.
A. F. Cozzolino, C. K. Brozek, R. D. Palmer, J. Yano, M. Y. Li
and M. Dinca, J. Am. Chem. Soc., 2014, 136, 3334ꢀ3337.
F. Heims, F. F. Pfaff, S. L. Abram, E. R. Farquhar, M. Bruschi, C.
Greco and K. Ray, J. Am. Chem. Soc., 2014, 136, 582ꢀ585.
Y. Dede, X. H. Zhang, M. Schlangen, H. Schwarz and M. H.
Baik, J. Am. Chem. Soc., 2009, 131, 12634ꢀ12642.
W. M. Khairul, M. A. Fox, P. A. Schauer, D. AlbesaꢀJove, D. S.
Yufit, J. A. K. Howard and P. J. Low, Inorg. Chim. Acta, 2011,
374, 461ꢀ471.
27.
28.
29.
L. Y. Tian, Y. M. Liu, G. X. Tian, X. H. Wu, Z. Li, J. F. Kou, Y.
P. Ou, S. H. Liu and W. F. Fu, Dalton Trans., 2014, 43, 4093ꢀ
4101.
P. B. Chatterjee, O. GoncharovꢀZapata, G. J. Hou, O. Dmitrenko,
T. Polenova and D. C. Crans, Eur. J. Inorg. Chem., 2012, 4644ꢀ
4651.
A. P. de Silva, Chem. Asian J., 2011, 6, 750ꢀ766.
4 | J. Name., 2012, 00, 1-3
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