Novel highly efficient fluoroionophores with a peri-effect and strong electron-donating receptors: TICT-promoted PET and signaling response to transition metal cations with low background emission

Article abstract of DOI:10.1016/S0040-4039(03)00186-2

Novel fluoroionophores with piperazine frameworks as receptors for transition metal cations have been designed with the aid of calculation and synthesized. They exhibited low background emission and highly efficient fluorescence enhancements upon complexation with different transition metal cations, which could be ascribed to the special contribution of the TICT-promoted PET processes caused by the peri-effect and strong electron-donating receptors.

Full text of DOI:10.1016/S0040-4039(03)00186-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2087–2091
Novel highly efficient fluoroionophores with a peri-effect and
strong electron-donating receptors: TICT-promoted PET and
signaling response to transition metal cations with low
background emission
Yi Xiaoa,b and Xuhong Qiana,*
aState Key Laboratory of Fine Chemicals, Dalian University of Technology, PO Box 40, Dalian 116012, China
bShanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, PO Box 544,
Shanghai 200237, China
Received 4 November 2002; revised 9 January 2003; accepted 17 January 2003
Abstract—Novel fluoroionophores with piperazine frameworks as receptors for transition metal cations have been designed with
the aid of calculation and synthesized. They exhibited low background emission and highly efficient fluorescence enhancements
upon complexation with different transition metal cations, which could be ascribed to the special contribution of the
TICT-promoted PET processes caused by the peri-effect and strong electron-donating receptors. © 2003 Elsevier Science Ltd. All
rights reserved.
The search for highly sensitive and selective
fluoroionophores for transition and heavy metal ions is
currently attracting great interest all over the world.1
Photoinduced electron transfer (PET) fluoroionophores
in the ‘fluorophore-spacer-receptor’ format,2 and
intramolecular charge transfer (ICT) ones in the
‘fluorophore-receptor’ format3 are the two most impor-
tant classes.
improves
the
sensitivities
of
these
PET
fluoroionophores; Brown et al.4c studied the relation-
ship between alkyl spacer length (or the carbon number
between the two nitrogens) and PET sensitivity. Since
the two nitrogen atoms of the receptor play critical
roles for the photophysical processes, there are possibly
ways to improve the sensitivity of fluorescence
response. We suggested that the PET of the
fluoroionophores could be strengthened via TICT
(twisted ICT), so that even slight differences in the
disturbance to the receptor caused by the cations might
be translated into a sharply different FE factor of a
fluorophore. To achieve these requirements, a semi-
rigid piperazine substituent with a peri-effect, and as a
PET fluoroionophores4 with ‘amino-alkyl-amino’ type
receptors, exhibit considerable fluorescence enhance-
ment (FE) upon binding to a great variety of transition
metal cations. Samanta et al.4a,b found that an increase
of electron-deficiency of the fluorophore moieties
Scheme 1. The studied compounds.
* Corresponding author. E-mail: xhqian@dlut.edu.cn
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00186-2

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Y. Xiao, X. Qian / Tetrahedron Letters 44 (2003) 2087–2091
strong electron-donating receptor, which could result in
TICT-promoted PET processes, was successfully used
to build new fluoroionophores (A5, B3, C3) with high
sensitivity (Scheme 1).
photogenerated electron field could accelerate the PET
process if properly orientated. The S1 of A4 and A5 had
similar electron distribution to that of A2, while S1 of
A3 was similar to A1. So, A4 and A5 also formed TICT
states and a very strong positive electron field on the
4-position nitrogen following excitation to accelerate
the PET process, while A3 formed an ordinary ICT
state and a relatively weaker electron field.
The origin of this molecular design can be traced back
to A1 and A2, two derivatives of 4-amino-1,8-dicyano-
naphthene (ADCN),5 A2 with the stronger electron-
donating dimethylamino, exhibits much weaker
fluorescence than A1 with a butylamino electron-donor.
ZINDO/S calculations showed that (Fig. 1) in the
lowest excited singlet state (S1) of A1, the electron
density on the nitrogen atom at the 4-position decreases
greatly (compared with ground state S0, not listed here),
but still remains in small part. However, in the S1 of
A2, the electron density on the nitrogen at position 4
totally disappeared.
The distance between the two nitrogen atoms in the
‘amino-alkyl-amino’ type receptor was also crucial in
determining the PET rate:9 a short distance favors
orbital overlap. The molecular mechanics calculations
(Hyperchem 6.0) provided NꢀN distances of 3.173,
,
3.265 and 2.807 A for A3, A4, and A5 respectively; this
difference in the distances is understandable in terms of
steric factors. For A4, the hindrance from the peri-pro-
ton and the N-methyl group make the dimethyl-
aminoethyl group adopt an extended geometry, for A5,
the structure of the piperazine ring prevents the geome-
try from extending, while A3 adopts a geometry with
little steric hindrance. A5 could be reasonably expected
to undergo the fastest PET process, and as for A3 and
A4 it is impossible to decide which is faster because A4
has a stronger photogenerated electron field, while A3
has the shorter NꢀN distance.
Obviously, A2 formed a TICT6 excited state of much
higher polarity than A1, which was non-radiative7
because of rapid internal conversion (or intersystem
crossing) to ground state (or triplet state). The dimethyl-
amino made a double contribution to the TICT state:
its strong electron-donating effect stabilized the highly
polar state, and the pretwisted geometry due to steric
hindrance between the peri-proton and N-methyl group
favor a further twist to form the TICT state.
A4 and A5 were synthesized (Scheme 2) with high yields
via substitution reactions of 4-nitro-1,8-dicyanonaph-
thalene with the corresponding amine, and identified
via ESI MS, NMR, IR etc.10 This reaction took advan-
tage of the mild conditions for nucleophilic substitution
The study on A1 and A2 inspired us to design A4 and
A5 (with A3 as reference) for the possibility of obtain-
ing fluoroionophores in a TICT-promoted PET mecha-
nism. As de Silva8 had previously suggested,
a
Figure 1. ZINDO/S calculation of the electron distribution of A1, A2, A3, A4 and A5 in the singlet excited state.
Scheme 2. Synthetic procedure for A4 and A5. (a) NaNO3, H2SO4, rt 3 h, 75% yield. (b) Sulfamide, anhydrous ethanol, dry HCl,
reflux 3 h, 85% yield. (c) Under vacuum, heating to 220°C, 30 min, 68% yield. (d) Corresponding amines, DMSO, rt 16 h, 82%
and 85% yield for A4 and A5, respectively.

Y. Xiao, X. Qian / Tetrahedron Letters 44 (2003) 2087–2091
2089
by readily-oxidizable amines, over our previously
reported procedure5 with 4-bromo-1,8-dicyanonaph-
thalene as a precursor of substitution carried out under
relatively high temperature. The key intermediate 4-
nitro-1,8-dicyanonaphthalene, was readily synthesized
via a three-step procedure (nitration, cyclization, and
thermal decomposition) from acenaphthalenequinone,
and each step proceeded in good yield. The emission
properties of A4, A5 and reference compound A3, were
also recorded. In the absence of cations, the fluores-
cence quantum yields (FF) of A3, A4 and A5 in ethanol
were 0.051, 0.015 and 0.006, respectively.
fluoroionophores,11 and the influence of trace amounts
of protons generated by hydration of the metal salts is
probably small enough to be ignored, compared to the
influence of the cation-complexation itself.
The data in Table 1 clearly indicates that A3 exhibited
considerable FE toward most of the cations (except
Zn2+, and Hg2+), and the difference of FE factors for
different cations was not large; A4 exhibited somewhat
stronger FE, but the sensitivity was not improved.
Interestingly, A5 exhibited significant FE, and for dif-
ferent cations, the FE factors and changes were differ-
ent (also shown in Fig. 2): in the presence of a small
amount of Cr3+ and Fe3+, the FE factors were higher,
up to 102 and 114, respectively at concentrations of 25
and 15 mM. Cu2+ and Ni2+ also induced strong FE, up
to 82 and 71 fold at much higher concentrations (up to
150, 150 mM, respectively). Pb2+, Co2+ and Mn2+, had
smaller FE factors and high concentrations, and lastly,
no FE was observed in the presence of Hg2+ and Zn2+.
The fluorescence signaling high sensitivity of A5
towards different cations is possibly due to the amplifi-
cation effect of TICT-promoted PET (in terms of larger
FE factors) to the small difference in the cations–
fluroionophore interaction.
The weak fluorescence or low background emission of
A5 indicated the strongest fluorescence quenching,
which was caused by TICT-promoted PET, as TICT
made the positive–negative charge at the fluorophore
separate totally and more efficiently stimulate PET. A3
could just undergo the usual ICT-PET process, so the
fluorescence quenching effect was the weakest. A4 is
situated between A5 and A3, although it could undergo
TICT-promoted PET similar to A5, its long NꢀN dis-
tance lowered the PET rate to some extent. The TICT-
promoted PET occurring in A4 and A5 is different from
the usual PET2 or PET in the presence of ICT action.4
Transition metal cation sensitivity experiments were
carried out and, in Table 1, the maximum values of the
EF factors and the corresponding concentration of the
added cations are listed. Since some of the salts were
used in their hydrated forms, we purposely carried out
blank experiments: small amounts of water were added
to the ethanol solutions of the studied compounds, but
no apparent fluorescence change was observed, which
ruled out the disturbance from protons. Actually, dur-
ing our previous investigation, we had found that even
in water, transition metal cations and protons made
totally different fluorescence changes to the
In addition, a series of naphthalimides B and nitrobenz-
oxadiazoles C were designed and synthesized (Schemes
1 and 3). With B14c and C14b as references, some
similar phenomena or relationships to the A series were
found in the B and C series. B3 and C3 with a
4-methylpiperazino electron donor attached to the aro-
matic electron acceptor exhibited much stronger sensi-
tivity towards certain transition metal ions (Fe3+, Cr3+,
Cu2+), than the counterparts with (N%,N%-dimethyl-
aminoethylamino or (N,N%,N%-trimethyl)aminoethyl-
amino groups.
Table 1. Maximum of fluorescence enhancements (FE) of the fluoroionophores induced by transition cationsa
Cationsb
A3
A4
A5
B1
B2
B3
C1
C2
C3
[M]c/ FEd
mM
[M]/ FE
mM
[M]/ FE
mM
[M]/ FE
mM
[M]/ FE
mM
[M]/ FE
mM
[M]/ FE
mM
[M]/ FE
mM
[M]/ FE
mM
Fe3+
Cr3+
Mn2+
Co2+
Ni2+
Cu2+
Zn2+
Hg2+
Pb2+
25
25
18
15
25
25
19
20
12
16
18
18
15
25
300
200
150
150
114
102
20
53
71
82
0.6
0.03 300
57 300
50
25
26
25
11
19
23
24
15
50
200
100
100
100
31
30
15
22
26
29
10
50
200
200
200
200
106
104
27
65
60
25
25
200
200
200
75
68
62
14
33
41
63
15
25
200
100
300
75
69
63
10
23
30
65
40
75
200
100
300
50
157
122
29
13
56
300
200
150
100
200
300
250
7.0 200
11
15
14
0.5 200
−0.5 300
15
200
200
200
150
200
200
100
100
92
164
1.9 200
0.1 300
19
1.0 100
−0.1 100
21
2.2 100
0.5 100
24
3.4 300
0.1 300
69
2.8 200
2.1 300
28
0.7 200
0.1 200
22
0.2
0.05
15
200
250
200
300
200
200
250
a Experimental conditions: 5 mM ethanol solutions of the compounds were used at 298 K, uex=385, 355, 352, 422, 397, 377, 451, 467 and 454 nm
for A1, A2, A3, B1, B2, B3, C1, C2 and C3, respectively.
b Salts used for the experiments were CrCl3·6H2O, MnCl2·2H2O, FeCl3·H2O, CoCl2·6H2O, NiCl2·6H2O, CuCl2·H2O, ZnCl2, HgCl2, and
Pb(NO3)2.
c Represents the correlation of the metal ion for which FE was the maximum; a further increase in concentration beyond this led to fluorescence
quenching.
d With reference to the fluorescence intensity of the respective compound in the absence of cation.

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Y. Xiao, X. Qian / Tetrahedron Letters 44 (2003) 2087–2091
Fig. 2. The fluorescence enhancement of A5 (5 mM) in ethanol, induced by different cations.
Scheme 3. Synthetic procedures for B2, B3, C2 and C3. (e) DMSO, corresponding amines, rt 16 h, 88% and 92% yield for B2 and
B3, respectively. (f) Dichloromethane, corresponding amines, rt 30 min, 82% and 80% yield for C2 and C3, respectively.
The fluoroionophores (A5, B3, and C3) exhibited highly
sensitive fluorescence enhancements in the presence of
different transition cations. Their high sensitivity and
‘selectivity’ could be up to, or even higher than some
reported fluoroionophores3 with crown ether receptors,
and can be ascribed to the special contribution of the
TICT-promoted PET processes caused by the peri-
effect and strong electron-donating receptor.
Rice, T. E. Chem. Rev. 1997, 97, 1515 and references
cited therein; (b) de Silva, A. P.; Fox, D. B.; Huxley, A.
J. M.; Moody, T. S. Coord. Chem. Rev. 2000, 205, 41 and
references cited therein.
3. (a) Kollmannsberger, K.; Rurack, K.; Resch-Genger, U.
J. Phys. Chem. 1998, 102, 10211; (b) Le´tard, J. F.;
Lapouyade, R.; Rettig, W. Pure Appl. Chem. 1993, 65,
1705; (c) Shen, Y.; Sullivan, B. P. Inorg. Chem. 1995, 34,
6235; (d) Rurack, K.; Resch-Genger, U.; Bricks, J. L.;
Spieles, M. Chem. Commun. 2000, 2103.
Acknowledgements
4. (a) Ramachandram, B.; Sankaran, N. B.; Karmakar, R.;
Saha, S.; Samanta, A. Tetrahedron 2000, 56, 7041; (b)
Ramachandram, B.; Samanta, A. J. Phys. Chem. A 1998,
102, 10579; (c) Mitchell, K. A.; Brown, R. G.; Yuan, D.;
Chang, S.-C.; Utecht, R. E.; Lewis, D. E. J. Photochem.
Photobiol. A: Chem. 1998, 115, 157; (d) Huston, M. E.;
Haider, K. W.; Czarnik, A. W. J. Am. Chem. Soc. 1988,
110, 4460; (e) Gao, Y. Q.; Marcus, R. A. J. Phys. Chem.
A 2002, 106, 1956.
National Natural Science Foundation of China, and
the Ministry of Education of China supported this
study.
References
5. Qian, X.; Xiao, Y. Tetrahedron Lett. 2002, 43, 2991.
6. Rettig, W. Angew. Chem. Int., Ed. Engl. 1986, 25, 971.
7. (a) Jones, G.; Jackson, W. R.; Choi, C.-Y. J. Phys. Chem.
1985, 59, 294; (b) Bhattacharyya, K.; Chowdhury, M.
Chem. Rev. 1993, 93, 507.
8. de Silva, A. P.; Gunaratne, H. Q. N.; Habib-Jiwan, J.-L.;
McCoy, C. P.; Rice, T. E.; Soumillion, J.-P. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1728.
1. (a) Rurack, K. Spectrochim. Acta A: Mol. Biolmol.
Spectr. 2001, 14, 2161 and references cited therein; (b)
Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3 and
references cited therein; (c) Fabbrizzi, L.; Licchelli, M.;
Pallavicini, P.; Sacchi, D.; Taglietti, A. Analyst 1996, 121,
1763.
2. (a) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson,
T.; Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.;
9. Kavarnos, G. J.; Turro, N. J. Chem. Rev. 1986, 86, 401.

Y. Xiao, X. Qian / Tetrahedron Letters 44 (2003) 2087–2091
2091
10. A5. mp 178–180°C, 1H NMR (400 MHz, CDCl3) l
8.47–8.45 (d, J=8.4 Hz, 1H), 8.09–8.07 (d, J=7.2 Hz,
1H), 8.03–8.01 (d, J=7.6 Hz, 1H), 7.64–7.60 (t, J=8
Hz, 1H), 7.22–7.20 (d, J=8.0 Hz, 1H), 3.31 (br s,
-N(CH2CH2)2NCH3, 4H), 2.90 (br s, -N(CH2CH2)2-
NCH3, 4H), 2.55 (s, -N(CH2CH2)2NCH3, 3H); 13C NMR
(100 MHz, CDCl3) l 155.18, 138.58, 137.68, 130.59,
130.24, 128.61, 125.67, 117.42, 116.98, 115.49, 109.30,
102.45, 55.09, 52.83, 46.07; IR (KBr, cm−1) 2221, 2211,
1575, 1511, 1454, 1371; ESI MS [M+H]+ (m/z 277). A4.
oily product, 1H NMR (400 MHz, DMSO-d6) l 8.65–
8.63 (d, J=8.0 Hz, 1H), 8.29–8.27 (d, J=7.2 Hz, 1H),
8.17–8.15 (d, J=8.4 Hz, 1H), 7.76–7.74 (t, J=8 Hz, 1H),
7.34–7.32 (t, J=8.0 Hz, 1H), 3.38–3.42 (t, J=6.8 Hz,
CH3NCH2CH2N(CH3)2, 2H), 2.99 (s, CH3NCH2CH2N-
(CH3)2, 3H), 2.75–2.79 (t, J=6.8 Hz, CH3NCH2CH2N-
(CH3)2, 2H), 3.28 (s, CH3NCH2CH2N(CH3)2, 6H); 13C
NMR (100 MHz, DMSO-d6) l 156.11, 138.29, 137.57,
131.03, 130.83, 128.69, 125.18, 117.54, 117.01, 115.49,
108.99, 101.07, 56.90, 54.95, 45.71, 42.15; ESI MS [M+
H]+ (m/z 279). B2: oily product, 1H NMR (400 MHz,
CDCl3) l 8.51–8.49 (d, J=7.2 Hz, 1H), 8.46–8.44 (d,
J=8.4 Hz, 1H), 8.43–8.41 (d, J=8 Hz, 1H), 7.61–7.58 (t,
J=7.8 Hz, 1H), 7.16–7.14 (d, J=8 Hz, 1H), 4.14–4.10 (t,
J=7.4 Hz, NCH2CH2CH2CH3, 2H), 3.42–3.38 (t, J=6.8
Hz, CH3NCH2CH2, 2H), 3.03 (s, CH3NCH2, 3H), 2.61
(br s, CH2N(CH3)2, 2H), 2.22 (s, CH2N(CH3)2, 6H),
1.69–1.66 (m, NCH2CH2CH2CH3, 2H), 1.41–1.38 (m,
NCH2CH2CH2CH3, 2H), 0.95–0.92 (m, NCH2CH2CH2-
CH3, 3H); ESI MS: [M+H]+ (m/z 354). B3: mp 137–
139°C, 1H NMR (400 MHz, CDCl3) l 8.58–8.56 (d,
J=7.2 Hz, 1H), 8.52–8.50 (d, J=8.0 Hz, 1H), 8.40–8.37
(d, J=8.4 Hz, 1H), 7.71–7.67 (d, J=7.8 Hz, 1H), 7.24–
7.22 (d, J=8.0 Hz, 1H), 4.18–4.14 (t, J=7.3 Hz,
NCH2CH2CH2CH3, 2H), 3.35 (br s, N(CH2CH2)2NCH3,
4H), 2.83 (br s, N(CH2CH2)2NCH3, 4H), 2.45 (s,
N(CH2CH2)2NCH3, 3H), 1.73–1.69 (m, NCH2CH2CH2-
CH3, 2H), 1.48–1.44 (m, NCH2CH2CH2CH3, 2H), 0.99–
0.66 (m, NCH2CH2CH2CH3, 3H); IR (KBr, cm−1): 1691,
1656, 1590, 1509; ESI MS: [M+H]+ (m/z 352). C2: mp
1
107–109°C, H NMR (400 MHz, CDCl3) l 8.41–8.38 (d,
J=9.2 Hz, 1H), 6.13–6.11 (d, J=9.2 Hz, 1H), 4.24 (br s,
CH3NCH2-, 2H), 3.51 (s, CH3NCH2-, 3H), 2.73 (br s,
-CH2N(CH3)2, 2H), 2.37 (s, -CH2N(CH3)2, 6H); 13C
NMR (100 MHz, CDCl3) l 145.57, 144.90, 144.65,
135.32, 122.76, 101.46, 57.09, 53.84, 45.85, 42.01; ESI
MS: [M+H]+ (m/z 266). C3: mp 202–204°C, 1H NMR
(400 MHz, CDCl3) l 8.42–8.40 (d, J=8.8 Hz, 1H),
6.31–6.29 (d, J=9.2 Hz, 1H), 4.14–4.11 (t, J=4.8 Hz,
-N(CH2CH2)2NCH3, 4H), 2.68–2.66 (t, J=5.0 Hz,
-N(CH2CH2)2NCH3, 4H), 2.39 (s, NCH3, 3H); 13C NMR
(100 MHz, CDCl3) l 145.23, 144.91, 144.84, 135.17,
123.70, 102.72, 54.75, 49.54, 46.06; IR (KBr) cm−1: 1609,
1548, 1437, 1300; ESI MS: [M+H]+ (m/z 264), [M+Na]+
(m/z 286).
11. Grabchev, I.; Qian, X.; Xiao, Y.; Zhang, R. New J.
Chem. 2002, 26, 920.