A colorimetric ATP sensor based on 1,3,5-triarylpent-2-en-1,5-diones

Article abstract of DOI:10.1002/1521-3773(20010716)40:14<2640::AID-ANIE2640>3.0.CO;2-A

A new family of chromogenic ionophores for anion sensing has been developed with 1,35-triarylpent-2-en-1,5 diones. These species form yellow solutions that undergo a color change to magenta in the presence of certain inorganic ions or nucleotides, dependi

Full text of DOI:10.1002/1521-3773(20010716)40:14<2640::AID-ANIE2640>3.0.CO;2-A

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[11] The molar composition of this mixture prepared from silicic acid,
TPAOH, and NaOH: (TPA2O)(SiO2)4(Na2O)0.33(H2O)47.
[12] C. E. A. Kirschhock, R. Ravishankar, P. J. Grobet, P. A. Jacobs, J. A.
Martens, J. Phys. Chem. B 1999, 103, 4965 ± 4971.
[13] The molar composition of this mixture prepared from silicic acid and
TPAOH: (TPA2O)(SiO2)4(H2O)47; the suspension was gently heated
to 508C to initiate reaction.
1,3,5-triaryl-1,5-pentanedione derivative 1 after column chro-
matography (Scheme 1). The NMR (1H, 13C) and mass spectra
of 1 are consistent with the proposed formulation. The UV/
Vis spectrum of 1 shows bands in the range of 200 ± 300 nm
along with a band centered at 380 nm, which is responsible for
the pale yellow color of the receptor.
[14] The molar composition of the TEOS system: (TPA2O)(SiO2)3.75
-
(H2O)30(EtOH)15; in the silicic acid system, the sample was the final
product from the preparation of ref. [11].
[15] C. E. A. Kirschhock, R. Ravishankar, P. A. Jacobs, J. A. Martens, J.
Phys. Chem. B 1999, 103, 11021 ± 11027.
O
O
[16] R. Ravishankar, C. E. A. Kirschhock, B. J. Schoeman, P. Vanoppen,
P. J. Grobet, S. Storck, W. F. Maier, J. A. Martens, F. C. De Schryver,
P. A. Jacobs, J. Phys. Chem. B 1998, 102, 4588 ± 4597.
S
S
Me
Me
N
N
[17] a) J. N. Watson, A. S. Brown, L. E. Iton, J. W. White, J. Chem. Soc.
Faraday Trans. 1998, 94, 2181 ± 2186; b) S. L. Burkett, M. E. Davis, J.
Phys. Chem. 1994, 98, 4647 ± 4653; c) P. P. E. A. De Moor, T. P. M.
Beelen, R. A. Van Santen, Microporous Mater. 1997, 9, 117 ± 130;
d) T. A. M. Twomey, M. Mackay, H. P. C. E. Kuipers, R. W. Thomp-
son, Zeolites 1994, 14, 162 ± 168; e) B. J. Schoeman, Stud. Surf. Sci.
Catal. 1997, 105, 647 ± 654.
oder
+
O
–
a) DMF, ∆
b) Säulenchromatographie
ClO4
[18] R. Ravishankar, C. E. A. Kirschhock, B. J. Schoeman, D. De Vos, P. J.
Grobet, P. A. Jacobs, J. A. Martens in Proc. 12th Int. Zeolite Conf.,
Vol. III (Eds.: M. M. J. Treacy, B. K. Marcus, M. E. Bisher, J. B.
Higgins), Materials Research Society, Warrendale, 1999, pp. 1825 ±
1832.
O
O
S
S
Me
Me
N
N
oder
A Colorimetric ATP Sensor Based on
1,3,5-Triarylpent-2-en-1,5-diones**
O
O
O
O
Â
Â
Â
Felix Sancenon, Ana B. Descalzo, Ramon Martínez-
1
2
Â
Ä
Manez,* Miguel A. Miranda, and Juan Soto
Scheme 1. Synthesis of the 1,3,5-triaryl-1,5-pentanedione derivatives 1 and
2. The reaction is carried out in refluxing dimethylformamide (DMF) for
3 h, and subsequent column chromatography on alumina with CH2Cl2/
MeOH (50/1 v/v) as eluent provides 1 (35% yield) or 2 (50% yield).
The development of systems that are capable of sensing or
recognizing and are based on supramolecular concepts is an
area of current interest.[1] One of the most appealing
approaches involves the construction of chromoionophores.
Although such systems have been widely used for the analysis
of metal cations,[2] chromogenic sensors for the ªnaked-eyeº
sensing of anions are not common;[3] this is especially the case
in aqueous environments.[4]
We report here the synthesis of 1,3,5-triarylpent-2-en-1,5-
dione derivatives and demonstrate their ability to act as
colorimetric anion sensors. The new family of chromogenic
reagents is easily obtained by condensation of the 2,6-
diphenylpyrylium cation with N-functionalized anilines. For
instance, the reaction of N-phenyl-1-aza-7,10-dioxa-4,13-di-
thiacyclopentadecane with 2,6-diphenylpyrylium gave the
The 1,5-pentanedione system of 1 can be readily trans-
formed into the corresponding pyrylium ion (Scheme 2):[5]
Addition of nitric acid to solutions of 1 in 1,4-dioxane/water
(70/30 v/v) caused a dramatic change in color from yellow to
magenta. This change was accompanied by a new intense
O
O
O
O
S
S
S
S
N
N
Â
Â
Ä
[*] Dr. R. Martínez-Manez, F. Sancenon, A. B. Descalzo,
+ H+, _ H2O
Prof. M. A. Miranda, Dr. J. Soto
Departamento de Química
Â
Universidad Politecnica de Valencia
Camino de Vera s/n, 46071 Valencia (Spain)
Fax : (‡34)9-6-387-7349
O
O
O
+
E-mail: rmaez@qim.upv.es
[**] This research was supported by the Ministerio de Ciencia y Tecnología
(proyecto PB98-1430-C02-02, 1FD97-0508-C03-01, and AMB99-0504-
1
1(Cy)
Â
C02-01). F.S. also thanks the Ministerio de Educacion y Cultura for a
Doctoral Fellowship.
Scheme 2. Transformation of the 1,5-pentanedione 1 into the pyrylium
cation 1(Cy).
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Angew. Chem. Int. Ed. 2001, 40, No. 14

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band centered at 550 nm in the UV/Vis spectrum. We ascribe
this new band to the highly delocalized pyrylium cation
formed upon cyclization. This cation was isolated as the
perchlorate salt, and the spectroscopic characterization fully
supported the proposed formulation.
The changes in the absorption spectrum of 1 at neutral pH
values upon addition of anions such as chloride, bromide,
sulfate, and phosphate (as tetrabutylammonium salts) as well
as ATP, ADP, and GMP (as sodium salts) have also been
studied. The photograph in Figure 1 shows the color changes
Figure 1. Color changes induced on 1 (1.0 Â 10 4 m) at pH 6 in the presence
of the following anions in dioxane/water (70/30 v/v): from left to right: no
anion, bromide, chloride, phosphate, sulfate, GMP, ADP, and ATP.
Figure 2. a) Plot of the absorbance at 550 nm (A550) as a function of the pH
*
value for 1 ( ) and 1 in the presence of the anions chloride (Â), bromide
~
!
&
&
*
^
(
), sulfate ( ), phosphate ( ), ATP ( ), ADP ( ), and GMP ( ) in
after addition of equimolar amounts of these anions to 1 in
dioxane/water at pH 6. At this pH value, 1 forms a yellow
solution, either alone or in the presence of bromide, chloride,
phosphate, GMP, or ADP. Upon addition of sulfate, the
solution turns pale red. However, the most remarkable effect
is observed in the presence of ATP, whereby a bright magenta
color is fully developed.
dioxane/water (70/30 v/v). b) Absorbance at 550 nm of 1 (1.0 Â 10 4 m)
versus the logarithm of the ATP concentration at pH 6 in dioxane/water
(70/30 v/v).
from yellow to magenta. However, in the range pH 2 ± 4 there
is no selective pattern.
The analytical determination of anions, for instance in
water or in biological systems, is commonly carried out in the
presence of alkali and alkali earth cations. Therefore, we also
studied the effect that the metal ions Li , Na , K , Ca2‡, and
Mg2‡ (as their nitrate or perchlorate salts) have on solutions of
1 at pH 6. We found that there is no analytical interference, as
the presence of these cations does not induce any significant
color change.
A more detailed study has been carried out using basic
solutions of 1 containing equimolar amounts of the corre-
sponding anions, which were placed in dioxane/water (70/30
v/v) and subsequently acidified. The absorbance at 550 nm
was then monitored at different pH values; the results are
shown in Figure 2a. The pH values where the transformation
of the diketonic form (yellow) to the pyrylium form (magen-
ta) takes place are in the range 2 ± 5. Cyclization and color
development are thus a function of the pH value of the
medium. Enhancement of the absorbance at 550 nm is
ascribed to ring closure, as stated above. In general there is
no remarkable effect in the presence of the anions, except for
ATP, which is able to shift selectively the pH at which the
magenta color is observed towards higher values. At acidic pH
the situation is more complex, and in general all the anions
studied modify the pH value at which the solution changes
It can be concluded that there is a remarkable selective
ATP colorimetric detection. Hence, 1 is a selective chromo-
genic reagent for the sensing of ATP.[6] It is important to note
that the color change in 1 from yellow to magenta observed
upon addition of ATP is a very simple and easy ªnaked-eyeº
method. Additionally the pyrylium cation formed from 1,
responsible for the color change, has a molar absorptivity as
high as 30600 Lmol 1 cm 1; this allows sensitive spectropho-
tometric detection of the anion ATP. Figure 2b shows the
color response as a function of the ATP concentration at pH 6
([1] ˆ 9.5  10 5 m). Under these conditions, a linear response
range from 40 to 1100 ppm of ATP was found (higher ATP
concentrations result in the formation of a precipitate).
For the sake of comparison compound 2 was also synthe-
sized by reaction of N,N-dimethylaniline and 2,6-diphenyl-
pyrylium (Scheme 1). Figure 3 shows a photograph of the
color changes observed for 2 in dioxane/water (70/30 v/v) at
pH 6 in the presence of certain anions. There is a remarkable
switch from yellow to magenta in the presence of sulfate,
ADP, and ATP, whereas bromide, chloride, phosphate, and
GMP do not change the color of the 2 solution. The addition
‡
‡
‡
‡
‡
‡
of Li , Na , K , Ca2‡, or Mg2‡ had no effect. In the absence of
ATP and ADP, 2 can be considered as a selective chromogenic
reagent for sulfate.
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R
R
R
R
N
N
O
H
O
H
O
O
Ph
Ph
Ph
Ph
I
Figure 3. Color changes induced on 2 (1.0 Â 10 4 m) at pH 6 in the presence
of the following anions in dioxane/water (70/30 v/v): from left to right: no
anion, bromide, chloride, phosphate, sulfate, GMP, ADP, and ATP.
II
H+
H
N
Although further studies need to be carried out to correlate
selectivity and molecular architecture, some preliminary
considerations concerning the origin of the color change can
be advanced. First of all, the occurrence of ring closure as a
function of the pH value can be ascribed to the well-known
chemistry of the pyrylium cation. It has been reported that
nucleophilic attack of hydroxide anions or related nucleo-
philes over C2 results in ring opening, with the formation of
1,5-diketones (see form 1 in Scheme 2).[7] In a similar manner,
under certain circumstances, 1 is able to undergo intra-
molecular cyclization to restore structure 1(Cy). As stated
above, for 1 and 2 the color change is observed in the pH
range of about 2 ± 5. In this pH range protonation of the
aniline nitrogen atom is expected to take place. Consequently,
there is an apparent correspondence between protonation of
the amine and transformation of the diketone to the pyrylium.
To explain this observation, it should be considered that
cyclization must result from nucleophilic attack of the
hydroxyl group of the enol tautomer at C1 of the carbonyl
group (see structure I in Scheme 3). When the amine is not
protonated the electron density at C1 is too high; in other
words, the resonance structure II makes a significant contri-
bution and, hence, nucleophilic attack is disfavored. Upon
protonation, the nitrogen lone pair is engaged, and structure
II does not play a role. As a consequence, one would expect
C1 to be more electrophilic and thus subject to attack by the
enol.
To explain the color change observed in the presence of
certain anions, one should consider that structure I contains
functional groups such as amine, enol, and carbonyl that are
capable of coordinating anions through electrostatic forces or
hydrogen bonding. By such coordination it could be possible
to modulate the nucleophilic character of the hydroxyl oxygen
atom of the enol tautomer or the electrophilic character of the
C1 carbonyl carbon atom. A possible explanation might
involve coordination between the receptor 1 and ATP in such
a way that the pKa value of the amine increases, therefore
favoring cyclization at higher pH values.
R
R
O
H
O
Ph
Ph
Scheme 3. Proposed resonance structures involved in the ring closure of
1,5-pentanediones 1 and 2 to the corresponding pyrylium cations.
of biological importance, and cations do not induce any color
change. In this sense, 1 is a chromogenic reagent for ATP
sensing. In the absence of biological anions, 2 can be
considered a selective chromogenic reagent for sulfate.
Received: January 26, 2001 [Z16516]
[1] A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, J. M. A. Huxley,
C. P. McCoy, J. T. Rademacher, T. E. Rice, Chem. Rev. 1997, 97, 1515 ±
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2001, 113, 502 ± 532; Angew. Chem. Int. Ed. 2001, 40, 486 ± 516.
[2] See, for example, T. Hayashita, K. Kunogi, H. Yamamoto, S. Shinkai,
Anal. Sci. 1997, 13, 161 ± 166; T. Hayashita, N. Teramae, T. Kuboyama,
S. Nakamura, H. Yamamoto, H. Nakamura, J. Inclusion Phenom. Mol.
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J. Am. Chem. Soc. 2000, 122, 776 ± 780; M. Micheloni, M. Formica, V.
Fusi, P. Romani, R. Pontellini, P. Dapporto, P. Paoli, P. Rossi, B.
Valtancoli, Eur. J. Inorg. Chem. 2000, 51 ± 57.
Â
[3] J. L. Sessler, A. Andrievsky, V. Kral, V. Lynch, J. Am. Chem. Soc. 1997,
119, 9385 ± 9392; A. Metzger, E. V. Anslyn, Angew. Chem. 1998, 110,
682 ± 684; Angew. Chem. Int. Ed. 1998, 37, 649 ± 652; S. Watanabe, O.
Onogawa, Y. Komatsu, K. Yoshida, J. Am. Chem. Soc. 1998, 120, 229 ±
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8533 ± 8534; J. J. Lavigne, E. V. Anslyn, Angew. Chem. 1999, 111, 3903 ±
3906; Angew. Chem. Int. Ed. 1999, 38, 3666 ± 3669; C. B. Black, B.
Andrioletti, A. C. Try, C. Ruiperez, J. L. Sessler, J. Am. Chem. Soc.
1999, 121, 10438 ± 10439; P. A. Gale, L. J. Twyman, C. I. Handlin, J. L.
Sessler, Chem. Commun. 1999, 1851 ± 1852; H. Miyaji, W. Sato, J. L.
Sessler, Angew. Chem. 2000, 112, 1847 ± 1850; Angew. Chem. Int. Ed.
2000, 39, 1777 ± 1780; P. Anzenbacher, Jr., A. C. Try, H. Miyaji, K.
Jursikova, V. M. Lynch, M. Marquez, J. L. Sessler, J. Am. Chem. Soc.
2000, 122, 10268 ± 10272; H. Miyaji, J. L. Sessler, Angew. Chem. 2001,
113, 158 ± 161; Angew. Chem. Int. Ed. 2001, 40, 154 ± 157.
In conclusion we have synthesized a new family of easy-to-
prepare chromogenic reagents and have found a highly
selective color response against ATP in an aqueous ± organic
environment. Remarkably, ATP is capable of changing the
absorption spectrum of 1 in the pH range 4 ± 8, whereas
inorganic anions (with the exception of sulfate), other anions
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Â
[4] V. Kral, H. Furuta, K. Shreder, V. Lynch, J. L. Sessler, J. Am. Chem.
thermally stable only up to 8508C, whereas boron nitride
and silicon nitride decompose at much higher temperatures.[1]
The thermal lability of phosphorus(v) nitrides is an important
reason why the synthesis of highly condensed crystalline
nitridophosphates (molar ratio P:N > 1:2) is difficult. The
irreversible elimination of N2, which is the main process
during the thermal decomposition of phosphorus(v) nitrides,
can be suppressed by using high-pressure conditions. Recent-
ly, the synthesis of highly condensed nitridophosphates by
reaction of the respective metal azides with P3N5 was
successfully carried out at about 4 GPa and 13008C. We
obtained the alkali and alkaline earth nitridophosphates (e.g.
MIPN2, MIP4N7, M3IP6N11, MIIP2N4)[4] without thermal decom-
position of P3N5 or the reaction products.
By increasing the pressure further we have now been able
to synthesize the high-pressure phase g-P3N5. The reaction
was carried out at 15008C and 11 GPa with partially
crystalline P3N5 as starting material. The reaction was
performed by using a boron nitride capsule in a multianvil
assembly, which allowed the synthesis of about 50 mg g-P3N5
(see Experimental Section).
Soc. 1996, 118, 1595 ± 1607; H. Hisamoto, H. Tohma, T. Yamada, K.
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P. Pallavicini, A. Perotti, A. Manotti-Lanfredi, F. Ugozzoli, Angew.
Chem. 2000, 112, 3039 ± 3042; Angew. Chem. Int. Ed. 2000, 39, 2917 ±
2920.
[5] For a related transformation, see F. Pina, M. J. Melo, M. Maestri, P.
Passaniti, V. Balzani, J. Am. Chem. Soc. 2000, 122, 4496 ± 4498.
[6] For recently reported ATP fluorescent sensors, see M. T. Albelda,
M. A. Bernardo, E. García-EspanÄa, M. L. Godino-Salido, S. V. Luis,
M. J. Melo, F. Pina, C. Soriano, J. Chem. Soc. Perkin Trans. 2 1999,
2545 ± 2549; S. E. Schneider, S. N. OꢁNeil, E. V. Anslyn, J. Am. Chem.
Soc. 2000, 122, 542 ± 543; M. E. Padilla-Tosta, J. M. Lloris, R. Martínez-
ManÄez, T. Pardo, F. Sancenon, J. Soto, M. D. Marcos, Eur. J. Inorg.
Chem. 2001, 1221 ± 1226.
[7] G. Schwarzenbach, K. Lutz, Helv. Chim. Acta 1940, 23, 1147; E. N.
Marvell, G. Caple, T. A. Gosink, G. Zimmer, J. Am. Chem. Soc. 1966,
88, 619 ± 620.
Â
Â
The crystal structure of g-P3N5 (Table 1) was determined by
direct methods from powder X-ray diffraction data and
refined using the Rietveld method (Figure 1).[5] The novel
high-pressure modification consists of a polymeric three-
dimensional network structure of linked PN4 tetrahedra and
tetragonal-pyramidal PN5 units. In accord with the nomen-
High-Pressure Synthesis of g-P3N5 at 11 GPa
and 15008C in a Multianvil Assembly: A Binary
Phosphorus(v) Nitride with a Three-
Dimensional Network Structure from PN4
Tetrahedra and Tetragonal PN5 Pyramids**
Table 1. Atomic parameters and isotropic thermal displacement fac-
tors [pm2] of g-P3N5.[a]
Kai Landskron, Hubert Huppertz, Jürgen Senker, and
Wolfgang Schnick*
Atom
Wyckoff
position
x
y
z
Uiso
P1
P2
N1
N2
N3
2a
4c
2b
4c
4c
0
0
0.3114(10)
0.0420(9)
0.5159(15)
0.0768(9)
0.2196(12)
274(14)
360(10)
62(29)
214(19)
263(25)
Phosphorus(v) nitride, P3N5, has structural similarities to
the polymeric nonmetal nitrides a- and b-Si3N4 as well as to
cubic boron nitride (c-BN). These compounds are built up
from three-dimensional networks of linked TN4 tetrahedra
(Tˆ B, Si, P). In cubic boron nitride as well as in a- and b-
silicon nitride corner-sharing tetrahedra exclusively occur,
whereas in a-P3N5 corner- and edge-sharing PN4 units
exist.[1, 2] Recently the synthesis of cubic g-Si3N4 was reported.
This high-pressure modification, which crystallizes in the
spinel structure type, consists of SiN4 tetrahedra and SiN6
octahedra.[3]
0.8191(2)
0
0.8953(4)
0.7265(6)
1/2
1/2
0
1/2
[a] The temperature factor is defined by exp( 8p2 Uiso sin2 q/l2), space
group Imm2, a ˆ 1287.20(5), b ˆ 261.312(6), c ˆ 440.04(2) pm, Z ˆ 2.
With respect to its material properties phosphorus(v)
nitride differs significantly from BN and Si3N4: P3N5 is
[*] Prof. Dr. W. Schnick, Dipl.-Chem. K. Landskron, Dr. H. Huppertz,
Dr. J. Senker
Department Chemie der Ludwig-Maximilians-Universität
81377 München (Germany)
Fax : (‡49)89-2180-7440
E-mail: wsc@cup.uni-muenchen.de
[**] This work was supported by the Fonds der Chemischen Industrie and
the Deutsche Forschungsgemeinschaft (Gottfried-Wilhelm-Leibniz-
Programm). The authors thank Dr. D. Frost and Prof. Dr. D. C. Rubie,
Bayerisches Geoinstitut, Universität Bayreuth, as well as Dr. P.
Ulmer, ETH Zürich, for help in adapting the multianvil-technique.
Also many thanks to W. Wünschheim, Department Chemie, LMU
München for the development and programming of software for the
high-pressure experiments.
Figure 1. Observed (crosses) and calculated (line) X-ray powder diffrac-
tion pattern as well as difference profile (bottom line) of the Rietveld
refinement of g-P3N5. Positions of Bragg reflections are marked by vertical
lines. The diffraction pattern was obtained with a conventional STOE-
Stadi-P powder diffractometer (CuKa1, l ˆ 154.05 pm).
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