Origin of Chemiluminescence Accompanying the Reaction of the 9-Cyano-10-methylacridinium Cation with Hydrogen Peroxide

Article abstract of DOI:10.1021/jo0354387

The 9-cyano-10-methylacridinium cation possesses an electrophilic center at the carbon atom in position (9) susceptible to the addition of anions. The addition of OOH^- to this cation-in weakly acidic, neutral, or alkaline media-initiates processes leading to the formation of electronically excited 10-methyl-9-acridinone, which deactivates by light emission. The effect of changes in reactant concentrations and pH on emission decay with time, as well as other features of the accompanying chemiluminescence, were established. Calculations carried out at the semiempirical and density functional theory level demonstrated that initial addition of OOH^- and subsequent processes lead either to the elimination of OCNH (in weakly acidic and neutral media) or OCN^- (in alkaline media) and that their exothermicity is sufficiently high to generate electronically excited 10-methyl-9-acridinone. On the other hand, primary addition of OH^- to C(9) in alkaline media initiates the conversion of the cation to the nonexcited 10-methyl-9-acridinone. This relatively rapid process influences to a substantial extent the intensity of the chemiluminescence. The prospects for the analytical application of 9-cyano-10-methylacridinium salts are briefly outlined.

Full text of DOI:10.1021/jo0354387

Or igin of Ch em ilu m in escen ce Accom p a n yin g th e Rea ction of th e
-Cya n o-10-m eth yla cr id in iu m Ca tion w ith Hyd r ogen P er oxid e
9
†
‡
‡
‡
†
,†
A. Wr o´ blewska, O. M. Huta, S. V. Midyanyj, I. O. Patsay, J . Rak, and J . Bła z˘ ejowski*
Faculty of Chemistry, University of Gda n´ sk, J . Sobieskiego 18, 80-952 Gda n´ sk, Poland, and Faculty of
Chemistry, Ivan Franko L’viv National University, Kyrylo and Mefodiy 6, 79005 L’viv, Ukraine
bla@chem.univ.gda.pl
Received October 1, 2003
The 9-cyano-10-methylacridinium cation possesses an electrophilic center at the carbon atom in
position (9) susceptible to the addition of anions. The addition of OOH- to this cationsin weakly
acidic, neutral, or alkaline mediasinitiates processes leading to the formation of electronically
excited 10-methyl-9-acridinone, which deactivates by light emission. The effect of changes in reactant
concentrations and pH on emission decay with time, as well as other features of the accompanying
chemiluminescence, were established. Calculations carried out at the semiempirical and density
-
functional theory level demonstrated that initial addition of OOH and subsequent processes lead
-
either to the elimination of OCNH (in weakly acidic and neutral media) or OCN (in alkaline media)
and that their exothermicity is sufficiently high to generate electronically excited 10-methyl-9-
-
acridinone. On the other hand, primary addition of OH to C(9) in alkaline media initiates the
conversion of the cation to the nonexcited 10-methyl-9-acridinone. This relatively rapid process
influences to a substantial extent the intensity of the chemiluminescence. The prospects for the
analytical application of 9-cyano-10-methylacridinium salts are briefly outlined.
1
. In tr od u ction
Among the numerous chemical processes that lead to
oxidation leads to a larger or smaller number of elec-
tronically excited 10-methyl-9-acridinone (MA*) mol-
1-19
ecules that emit light upon radiative deactivation.
The
chemiluminescence, of importance are those occurring
emission is influenced by numerous organic and inorganic
with the involvement of 10-methylacridinium derivatives,
substances, and this constitutes a basis for the analytical
usually substituted at the carbon atom (9).1
-10
These
7,9,10,20
application of 10-methylacridinium derivatives.
On
compounds are relatively easily oxidized with hydrogen
the other hand, 10-methylacridinium chemiluminogens
are widely used as fragments of chemiluminescent labels
peroxide,3
,4,6,8,9,11
other peroxides, persulfates, or mo-
12
13
lecular oxygen1
4-19
in neutral or alkaline media. The
which have been successfully applied in medical, bio-
chemical, and environmental analyses.4
,6,9,10
These are
*
Corresponding author. Phone: +48 58 345 03 31. Phone/fax: +48
the reasons for our interest in 9-cyano-10-methylacri-
dinium cation (CMA ), which has not been very thor-
oughly investigated from this point of view.
5
8 345 04 64.
+
†
University of Gda n´ sk.
Ivan Franko L’viv National University.
‡
(
(
(
(
1) Rauhut, M. M. Acc. Chem. Res. 1969, 2, 80.
2) White, E. H.; Roswell, D. F. Acc. Chem. Res. 1970, 3, 541.
3) McCapra, F. Acc. Chem. Res., 1976, 9, 201.
The 9-cyano-10-methylacridinium cation (Chart 1) has
2
1-23
long been known as a component of acridinium salts.
Quite recently, we determined the structure of 9-cyano-
0-methylacridinium hydrogen dinitrate in the crystal-
4) Weeks, I.; Beheshti, I.; McCapra, F.; Campbell, A. K.; Woodhead,
J . S. Clin. Chem. 1983, 29, 1474.
(
(
1
5) Abdel-Lalif, M. S.; Guilbault, G. G. Anal. Chem. 1988, 60, 2671.
6) Zomer G.; Stavenuiter, J . F. C.; Van den Berg, R. H.; J ansen, E.
2
4
line phase, which encouraged us to undertake investi-
+
H. J . M. Pract. Spectrosc. 1991, 12, 505.
7) Warner, I. M.; Soper, S. A.; McGown, L. B. Anal. Chem. 1996,
8, 73R.
gations into the chemiluminescent properties of CMA .
(
6
(
(
(
8) Rak, J .; Skurski, P.; Blazejowski, J . J . Org. Chem. 1999, 64, 3002.
9) Dodeigne, C.; Thunus, L.; Lejeune, R. Talanta 2000, 51, 415.
10) Zomer, G.; J acquemijns, M. In Chemiluminescence in Analytical
(17) Suzuki, N.; Kazui, Y.; Kato, M.; Izawa, Y. Heterocycles 1981,
16, 2121.
(18) Suzuki, N.; Kazui, Y.; Tsukamoto, T.; Kato, M.; Izawa, Y. Bull.
Chem. Soc. J pn. 1983, 56, 1519.
Chemistry; Garcia-Campana, A. M., Baeyens, W. R. G., Eds.; Marcel
Dekker: New York, 2001; p 529.
(19) Kamiya, I.; Sugimoto, T.; Yamabe, K. Bull. Chem. Soc. J pn.
1984, 57, 1735.
(20) Rokicioglu, Y.; Schulman, J . M.; Schulman, S. G. In Chemilu-
minescence in Analytical Chemistry: Garcia-Campana, A. M., Baeyens,
W. R. G., Eds.; Marcel Dekker: New York, 2001; p 105.
(21) Kaufmann, C.; Albertini, A. Ber. Dtsch. Chem. Ges. 1909, 42,
1999, 2002.
(
11) White, E. H.; Roswell, D. F.; Dupont, A. C.; Wilson, A. A. J .
Am. Chem. Soc. 1987, 109, 5189.
12) Sakanishi, K.; Kato, Y.; Mizukoshi, E.; Shimizu, K. Tetrahedron
Lett. 1994, 35, 4789.
13) Cass, M. W.; Rapaport, E.; White, E. H. J . Am. Chem. Soc. 1972,
4, 3168.
(
(
9
3
(14) Happ, J . W.; J anzen, E. G.; Rudy, B. C. J . Org. Chem. 1970,
(22) Kaufmann, C.; Albertini, A. Ber. Dtsch. Chem. Ges. 1911, 44,
2052.
5, 3382.
(
(
15) Happ, J . W.; J anzen, E. G. J . Org. Chem. 1970, 35, 3396.
16) Rapaport, E.; Cass, M. W.; White, E. H. J . Am. Chem. Soc. 1972,
(23) McCapra, F.; Richardson, D. G. Tetrahedron Lett. 1964, 3167.
(24) Huta, O. M.; Patsaj, I. P.; Konitz, A.; Meszko, J .; Blazejowski,
J . Acta Crystallogr., Sect. C 2002, C58, o295.
9
4, 3160.
1
0.1021/jo0354387 CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/11/2004
J . Org. Chem. 2004, 69, 1607-1614
1607

Wr o´ blewska et al.
CHART 1. Ca n on ic Str u ctu r e of CMA+ w ith th e
Nu m ber in g of Atom s In d ica ted
Absorption spectra were recorded in 1 cm quartz
cuvettes.
2
.3. Ca lcu la tion s. Unconstrained geometry optimiza-
2
7
tions employing the EF algorithm were performed at
the level of the semiempirical PM328 and PM3/CI, as
29
3
0
well as the density functional theory (DFT) level with
the 6-31G** basis set.31 The density functional calcula-
tions were carried out with the hybrid B3LYP func-
tional.3
2-34
After completion of each optimization, the
3
0,31
Hessian matrix was calculated
to check the nature
of the stationary point and to compute the vibrational
frequencies. PM3 was chosen since it performs better
3
5
We had come across an early publication by Radzisze-
wski, who reported for the first time that chemilumines-
cence accompanies the reaction of the synthetic organic
compound lophine (2,4,5-triphenyl-1H-imidazole) with
than other MNDO-type semiempirical methods. It also
supplied the initial structures for the DFT geometry
optimizations. The use of two independent methods (PM3
and DFT) provided a broader insight into the mechanism
of the ongoing processes. The solvent effect was included
in the PM3 calculations by means of the conductor-like
screening model (COSMO) (assuming molecular shape
cavity).36 In the DFT approach, the presence of solvent
was modeled at the level of the polarized continuum
2
5
oxygen in strongly alkaline media. Later on, McCapra
et al.2
3,26
found that oxidation of CMA with hydrogen
+
peroxide in alkaline water-ethanolic media produces
light. Others noted that the chemiluminescence ac-
companying the oxidation of 10-methylacridinium cations
with O
2
in aqueous alkaline media is enhanced in the
model (PCM) (UAHF radii were used to obtain the
presence of KCN.1
4,15,17
The emitting entity was always
37,38
molecular cavity),
in which single-point calculations
MA*. This brief overview indicates that little is known
about the origin of the chemiluminescence produced by
were carried out for the structures optimized in the
gaseous phase. The zero-point energy, thermal contribu-
tions to energy from vibrations, rotations, and transla-
tions, and also the entropy term were calculated in the
+
CMA . We thus undertook investigations in order to
+
discover the behavior of CMA and the principal features
3
9
of the chemiluminescence accompanying its reaction with
hydrogen peroxide. We further carried out calculations
in order to discover the principal reaction pathways. Last,
rigid-rotor harmonic-oscillator approximation using
4
0
standard statistical thermodynamics routines. These
terms were subsequently used to convert the electronic
energy into enthalpy and Gibbs’ free energy at an
ambient temperature of 298.15 K and a pressure of 1
atm. The PM3 (PM3(COSMO)) and the PM3/CI calcula-
tions were carried out using the MOPAC 2000 molecular
+
we explored the possible analytical uses of CMA .
2
. Meth od s
.1. Syn th esis. 9-Cyano-10-methylacridinium hydro-
2
41
orbital package and the DFT (DFT(PCM))-GAUSSIAN
gen dinitrate was prepared by the oxidation of 9-cyano-
42
9
8 program package. DFT calculations were partially
2
1,22
23
1
0-methylacridan
pound was identified by the X-ray method.
.2. Ch em ilu m in escen ce a n d Sp ectr a l In vestiga -
with dilute nitric acid. The com-
2
4
(
27) Baker, J . J . Comput. Chem. 1986, 7, 385.
2
(28) Stewart, J . J . P. J . Comput. Chem. 1989, 10, 209, 221.
tion s. Chemiluminescence investigations were carried
out using a “homemade” spectrochemiluminometersa
spectrofluorometer modified by using high brightness
optics, a collimating sphere, and a sensitive photomul-
tiplier (for the 320-650 nm region). All measurements
were done in a quartz cuvette of 1 cm optical length and
(29) Armstrong, D. R.; Fortune, R.; Perkins, P. G.; Stewart, J . J . P.
J . Chem. Soc., Faraday Trans. 2 1972, 68, 1839.
30) Density Functional Methods in Chemistry; Labanowski, K. J .,
Andzelm, J . W., Eds.; Springer-Verlag: New York, 1991.
(31) Hehre, W. J .; Radom, L.; Schleyer, P. v. R.; Pople, J . A. Ab initio
Molecular Orbital Theory; Wiley: New York, 1986.
(
(
(
32) Becke, A. D. Phys. Rev. A 1988, 38, 3098.
33) Becke, A. D. J . Chem. Phys. 1993, 98, 1372, 5648.
-
4
-6
1
0 mL volume. Initially, known volumes of 10 -10
M
(34) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(35) Stewart, J . J . P. J . Comput.-Aided Mol. Des. 1990, 4, 1.
+
-3
CMA in 10 M HNO
of 4-10 M H O in water. Next, 4 mL of this mixture
3
were mixed with known volumes
(
36) Klamt, A.; Schuurmann, G. Z. J . Chem. Soc., Perkin Trans. 2
1993, 799.
(37) Tomasi, J .; Persico, M. Chem. Rev. 1994, 94, 2027.
38) Barone, V.; Cossi, M.; Mennucci, B.; Tomasi, J . J . Chem. Phys.
-
6
2 2
was poured into the cuvette, which was then placed in
the spectrochemiluminometer compartment. After this,
(
1
997, 107, 3210.
1
mL of buffer or an appropriate aqueous solution of
(39) Baer, T.; Hase, W. L. Unimolecular Reaction Dynamics; Oxford
University Press: New York, 1996.
NaOH was added to the cuvette, which initiated chemi-
luminescence. This moment was taken as the initial time
(
(
40) Dewar, M. J . S.; Ford, G. P. J . Am. Chem. Soc. 1977, 99, 7822.
41) Stewart, J . J . P. MOPAC 2000; Fujitsu Ltd.: Tokyo, J apan,
in all experiments. The following buffers were used: CH
COOH/CH COONa (pH ) 4-5), NaH PO /Na HPO (pH
5-8), H BO /NaOH (pH ) 8-10), NaHCO /Na CO
pH ) 10-11) and the appropriate NaOH solutions (pH
11). Only during the recording of chemiluminescence
3
-
1999.
(42) Frish, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
3
2
4
2
4
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J . A.;
Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.; Daniels,
A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .; Barone, V.;
Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma,
K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J . B.;
Cioslowski, J .; Ortiz, J . V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Challacombe, M.; Gill, P. M. W.; J ohnson, B.; Chen, W.; Wong, M. W.;
Andres, J . L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople,
J . A. GAUSSIAN 98, Revision A.9; Gaussian, Inc.: Pittsburgh, PA,
1998.
)
(
3
3
3
2
3
>
spectra did the emitted radiation pass through a mono-
chromator. In other experiments, the whole radiation was
directed to the photomultiplier.
(
(
25) Radziszewski, B. Ber. Dtsch. Chem. Ges. 1877, 10, 70.
26) McCapra, F.; Richardson, D. G.; Chang, Y. C. Photochem.
Photobiol. 1965, 4, 1111.
1
608 J . Org. Chem., Vol. 69, No. 5, 2004

Reaction of the 9-Cyano-10-methylacridinium Cation with OOH-
SCHEME 1. P a th w a ys of th e Rea ction s of CMA+ w ith OOH- a
a
The solid arrows indicate processes involving molecules in the ground electronic state for which both thermodynamic and kinetic
characteristics were theoretically predicted, while the dashed arrows indicate hypothetical steps involving electronically excited 10-
methyl-9-acridinone molecules for which only thermodynamic data could be obtained.
done on the computers of the Tri-City Academic Com-
puter Network Center in Gda n´ sk, Poland (TASK).
The theoretically obtained characteristics enable de-
termination of the enthalpies (∆r,298H°) and Gibbs’ free
energies (free energies in the case of DFT(PCM)) (∆r,298G°)
of the reactions (r), as well as the enthalpies (∆a,298H°)
and Gibbs’ free energies (free energies in the case of DFT-
by solid-line arrows in Schemes 1 and 2). However, to
obtain some idea of how electronically excited 10-methyl-
9-acridinone could be formed, we calculated (only ther-
modynamic) data for the steps involving MA* (indicated
in Scheme 1 by dashed arrows). The rate constants (298k°)
for the gaseous phase reactions were obtained by apply-
ing the equation
(
1
PCM)) (∆a,298G°) of the activation (a) indicated in Scheme
, by following the basic rules of thermodynamics.43
RT
Nh
298k° )
exp[-∆a,298G°/(RT)]
Complete thermodynamic and kinetic (activation barri-
ers) characteristics were predicted only for steps involv-
ing molecules in the ground electronic state (indicated
resulting from transition state theory, and the reaction
completion time (298 99) from the formula
τ
(
43) Atkins, P. W. Physical Chemistry, 5th ed.; Oxford University
298τ
99
) ln 100/298k°
Press: Oxford, U.K., 1994.
J . Org. Chem, Vol. 69, No. 5, 2004 1609

Wr o´ blewska et al.
SCHEME 2. P a th w a ys of th e Rea ction s of CMA+ w ith OH-
where R, T, N, and h denote the gas constant, temper-
ature (298.15 K), Avogadro number, and Planck’s con-
stant, respectively.8
the presence of alkaline H
2
O
2
; at the same time, however,
a new band appears with a maximum at 330 nm. This
band can be attributed to the product of the primary
,43
-
+
addition of OOH to CMA .
3.2. Beh a vior of CMA+ in Alk a lin e Med ia . CMA+
is quite efficiently converted to MA in moderately alka-
line media without light emission (Figure 6). With its rate
3
. Resu lts a n d Discu ssion
.1. Ch em ilu m in escen ce Accom p a n yin g th e Re-
3
+
a ction of CMA w ith Hyd r ogen P er oxid e. The inter-
action of CMA with H
-1
-1
constant of 560 M
s , this unwanted bimolecular
+
2
O
2
in weakly acidic, neutral, or
45
reaction is thus relatively fast. It is believed to be the
major cause of the reduced quantum yields of chemilu-
minescence accompanying the oxidation of 10-methy-
alkaline media produces MA*, whose radiative deactiva-
tion is responsible for the chemiluminescence phenomena
4,45
(
Figure 1).4
The emission increases with time (Figures
1-3,6,8,9,45
lacridinium cations.
1
and 2), reaches a maximum, and decays within hours
3
.3. Or igin of Ch em ilu m in escen ce Du e to th e
in weakly acidic media or within minutes in weakly
alkaline media (Figure 2). In moderately alkaline media,
chemiluminescence is completed in under 1 min. The
total integral intensity of emission (Itotal) changes with
+
Rea ction of CMA w ith Hyd r ogen P er oxid e. The
+
-
primary steps of the reactions of CMA with either OOH
-
or OH are determined mainly by the location of the
electrophilic center in the cation. As indicated by the
pH (Figure 3) and H
2
O
2
concentration (Figure 4). In all
46
frontier orbital theory, LUMO distribution of an elec-
cases, very similar maximum values of Itotal are reached
at various abscissal values. The latter two dependencies
form a basis for the selection of the most suitable
conditions for analytical measurements.
trophilic species determines molecular centers sensitive
to nucleophilic attack. The value of the LCAO coefficient
+
of the p
z
atomic orbital in CMA ’s LUMO is ca. 10 times
higher at the endocyclic C(9) than at the cyano group
carbon atom (0.31 and 0.03, respectively). This implies
that C(9) rather than the carbon atom of the cyano group
is the site of the primary nucleophilic attack of the above-
+
CMA exhibits relatively strong absorption with maxima
at 265 and 385 nm (Figure 5). These bands diminish in
(
44) Bouzyk, A.; J ozwiak, L.; Kolendo, A. Yu.; Blazejowski, J .
Spectrochim. Acta, Part A 2003, 59, 543.
45) Wroblewska, A.; Huta, O. M.; Patsay, I. O.; Petryshyn, R. S.;
Blazejowski, J . Anal. Chim. Acta, in press (paper ACA225049).
(
(46) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: London, New York, 1976.
1
610 J . Org. Chem., Vol. 69, No. 5, 2004

Reaction of the 9-Cyano-10-methylacridinium Cation with OOH-
F IGURE 1. Spectra of the chemiluminescence accompanying
+
-5
the reaction of CMA (2.5 × 10 M) with H
2
O
2
(2.0 M) at pH
F IGURE 3. Total integral intensity (corresponding to the
)
6.1 recorded at 110-135 (1), 160-185 (2), and 215-240 (3)
whole spectrum and emission time) of the chemiluminescence
+
-7
time intervals (in s) following the mixing of the reagents.
(Itotal) accompanying the reaction of CMA (5.0 × 10 M) with
2 2
H O
(concentration in M: 1.0 (1); 0.1 (2); 0.01 (3); 0.0001 (4))
as a function of pH.
F IGURE 2. Integral intensity (corresponding to the whole
spectrum) of the chemiluminescence (I) accompanying the
+
-7
reaction of CMA (5.0 × 10 M) with H
1), 9.5 (2), and 11.1 (3) versus time following the mixing of
the reagents.
2 2
O (0.1 M) at pH: 5.5
(
F IGURE 4. Total integral intensity (corresponding to the
whole spectrum and emission time) of the chemiluminescence
+
-7
mentioned anions, despite the fact that the Mulliken
partial charge (DFT level) at C(9) is lower than at C(16)
(Itotal) accompanying the reaction of CMA (5.0 × 10 M) with
, at various concentrations, at pH: 7.2 (1); 9.2 (2); 9.9
3); and 11.0 (4).
2 2
H O
(
(0.17 and 0.25, respectively).
Another premise which must be taken into account is
and the elimination of OCN- leading to MA* (14) (step
X*). Pathway two assumes the attack of OH on the
-
the fact that H
OOH (the thermodynamic data (in kcal/mol) for the
2
O
2
reacts spontaneously with OH to yield
-
-
carbon atom of the cyano group in 3 (step XIII) and the
-
-
reaction H
2
O
2
+ OH f H
2
O + OOH are: -26.8
-
subsequent simultaneous elimination of OCN and H
2
O
(∆r,298H°; DFT), -27.8 (∆r,298G°; DFT) and -1.7 (∆r,298G°;
DFT(PCM)).
from the intermediate thus formed (17), leading to MA*
-
(
step XIV*). The possible addition of OH to the carbon
Taking into account the reaction pathways proposed
atom of the cyano group of 3 has been postulated by other
by other authors,1
4,15,17,23,26
as well as the information
47
authors. The process is probable since the LCAO
mentioned above, we considered the processes which
explain the experimental findings and are in accordance
with general chemical knowledge. The pathways of the
z
coefficients of s and p atomic orbitals of C(15) in LUMO
afford the substantial values of 0.19 and 0.08, respec-
tively. Moreover, the Mulliken partial charge (DFT level)
at C(15) in 3 is equal to 0.36, which further indicates such
a possibility. Pathway three assumes that the addition
product (3) undergoes cyclization to 10 (step VII), this
reaction being followed by the elimination of OCNH to
+
-
-
possible reactions of CMA with OOH and OH , outlined
in Schemes 1 and 2, respectively, emerge from a thorough
analysis of the results of theoretical calculations. Path-
-
way one represents the attack of OOH on carbon atom
9) of CMA (1) (step I), followed by the reaction of the
addition product (3) with OH (step VIII), the cyclization
of the anion so formed (11) to dioxoethane (13) (step IX),
+
(
-
(
47) Acheson, R. M. Acridines, 2nd ed.; J . Wiley and Sons: New
York, 1973.
J . Org. Chem, Vol. 69, No. 5, 2004 1611

Wr o´ blewska et al.
TABLE 1. Th er m od yn a m ic Da ta (in k ca l/m ol) for th e Elem en ta r y Step s of th e Rea ction s of CMA+ w ith OOH- a n d
-
a
OH
gaseous phase
aqueous phase
step no.
∆r,298H°
∆r,298G°
∆r,298H°
∆r,298G°
DFT (PCM)
-43.9
(
Schemes 1 and 2)
PM3
DFT
PM3
DFT
PM3 (COSMO)
I
II
III
IV
V
-163.7
-114.5
-106.0
-192.2
-141.6
-155.4
8.8
-165.5
-152.0
-102.1
-92.9
-182.5
-131.3
-145.5
10.5
-153.2
-5.1
1.7
1.8
-24.1
-12.8
-27.7
11.0
-142.5
-188.7
-129.2
-178.2
-30.5
-49.9
VI
VII
VIII
IX
X
-181.6
-2.8
-65.9
-171.6
-1.3
-66.4
-47.6
-1.0
-16.4
-45.4
-44.9
-8.8
5.9
4.8
4.8
-94.2
-11.9
-82.3
-89.4
-7.1
-106.6
-24.9
-81.8
-101.8
-20.1
-31.4
-101.8
-33.6
-81.7
0.1
-103.1
-28.5
-74.6
-97.2
-22.6
-14.0
-97.5
-17.4
-79.1
-4.5
*
X
XI
XII
XII
-95.9
-107.1
-107.5
*
XIII
XIV
-41.0
-78.5
-11.4
-69.5
12.8
-53.9
-107.9
-42.8
-130.7
-1.3
-122.6
*
XIV
XV
-90.0
-101.6
-91.4
*
XV
XVI
8.5
9.2
0.1
4.2
XVII
XVIII
-48.9
-78.3
4.0
-25.8
-87.3
-48.7
-92.2
-10.4
-56.4
3.7
-25.3
-100.3
-14.3
-90.4
-90.1
-15.5
-11.0
-3.2
*
XVIII
XIX
-55.3
-73.8
6.5
-10.0
-77.9
10.6
-74.9
-4.6
-21.0
-66.6
-12.9
-26.3
-10.4
-5.5
-19.5
-17.2
XX
14.9
XXI
0.7
-10.6
-42.9
-9.8
-6.0
XXII
XXIII
XXIV
-53.5
-9.6
13.0
-4.6
-13.8
-14.2
-14.9
a
∆
r,298H° and ∆r,298G°, respectively, represent the enthalpy and Gibbs’ free energy (gaseous phase) or free energy (aqueous phase) of
b
the reaction corresponding to the relevant step number at temperature 298.15 K and standard pressure (1 atm). The thermodynamic
characteristics correspond to the processes proceeding in the ground electronic state and the hypothetical steps (indicated by an asterisk)
involving 10-methyl-9-acridinone molecules in the electronically excited state.
F IGURE 5. Absorption spectra of CMA+ (1.0 × 10 M) at
-5
+
-5
-
F IGURE 6. Conversion of CMA (1.0 × 10 M) to MA at pH
pH ) 3 (1) and the probable product of the addition of OOH
+
-5
) 8.5 followed by the recording of absorption spectra at 45-
to it (2) (CMA ) 2.5 × 10 M; H
2 2
O ) 1.5 M; pH ) 8.1).
6
5 (1), 90-110 (2), 135-155 (3) and 225-245 (4) time intervals
(
in s) following the mixing of the reagents; the absorption
yield MA* (14) (step XVIII*). Pathway four reflects the
direct elimination of OCNH from 3 without a cyclic
intermediate (step XV*). One can imagine that either
OCNH or NCOH occur as products of steps XV(XV*) or
XVIII (XVIII*). We assumed that OCNH is formed, since
it is thermodynamically more stable than the other
isomer by -22.3 kcal/mol (DFT level). To complete the
picture, we also considered what would happen if OOH-
were first to attack the carbon atom of the cyano group
-5
spectrum of MA (1.0 × 10 M) is given by (5).
products (4 and 5) then being converted to MA* (steps
XVI, XVII and XVIII*). Now OH anions are not involved
-
in pathways three and four, so if the activation barriers
corresponding to steps XV or VII and XVIII were moder-
ate, this could account for the long-lasting chemilumi-
nescence observed in weakly acidic and neutral solutions.
The theoretically predicted thermodynamic data for all
the reaction steps are given in Table 1, while Table 2
+
in CMA (steps II and III), with the intermediate
1
612 J . Org. Chem., Vol. 69, No. 5, 2004

Reaction of the 9-Cyano-10-methylacridinium Cation with OOH-
TABLE 2. Kin etic Ch a r a cter istics of th e Elem en ta r y Step s in th e Rea ction of CMA+ w ith OOH- a n d OH- a
gaseous phase
aqueous phase
step no.
Schemes 1 and 2)
VII
∆a,298H°
∆a,298G°
298k° (298τ °99)
∆a,298H°
PM3 (COSMO)
76.2
∆a,298G°
(
PM3
DFT
PM3
84.4
DFT
PM3
DFT
DFT (PCM)
-
50
83.2
10.3
3.0
8.1 × 10
5.7 × 10
4
9
(
(
(
)
5
IX
10.1
2.8
2.6 × 10
15.7
17.2
-
5
1.8 × 10
5.3 × 10
)
1
0
X
8.7 × 10-11)
9
XII
3.5
4.8
3.9
5.5
8.3 × 10
1.8
10.6
50.6
27.1
5.2
5.5 × 10 10)
-
(
1
1
8
XIV
XVb
XVIII
XX
1.2
48.8
33.8
11.7
52.0
22.0
1.3
49.3
33.3
10.4
51.0
22.0
6.7 × 10
5.4 × 10
27.2
47.9
35.5
33.6
45.4
24.1
-
12
-9
(
(
(
(
(
(
6.9 × 10
4.3 × 10
1.0 × 10
2.5 × 10
1.8 × 10
)
(8.6 × 10
)
-24
-26
50.8
28.5
2.5
51.6
28.4
2.0
9.8 × 10
(4.7 × 10
2
4
25
)
)
-
12
-9
9.8 × 10
8
1
2
)
(4.7 × 10 )
11
5
1.5 × 10
2.0 × 10
-
-
5
-11
3.1 × 10
2.5 × 10
1.8 × 10
)
(2.3 × 10
5.2 × 10
(8.9 × 10
)
25
-11
XXI
XXIII
34.1
13.0
31.5
12.7
28.4
18.2
2
5
10
)
)
-
4
3
4.9 × 10
3.2 × 10
3
-3
9.4 × 10 )
(1.4 × 10
)
a
All characteristics apply to processes involving molecules in the ground electronic state. ∆a,298H° and ∆a,298G° (both in kcal/mol) represent
the enthalpy and Gibbs’ free energy (gaseous phase) or free energy (aqueous phase) of activation, respectively, at temperature 298.15 K
-
1
and standard pressure (1 atm). 298k° (in s ) and 298τ °99 (in s) respectively denote the rate constant and the time after which the reaction
b
is 99% complete. Activation barriers correspond to the HOCN elimination from 3.
contains kinetic data for the steps involving molecules
in the ground electronic state. Additionally, the PM3- and
DFT-optimized geometries originating from the acridine
of HOCN, and not the more stable OCNH, from 3, which
suggests that the actual barrier might be lower.) The
overall values of the thermodynamic functions for path-
ways one, two and four are high enough to ensure
electronic excitation of the 10-methyl-9-acridinone formed.
+
-
molecules produced by the reaction of CMA with OOH
-
or OH are shown in Figures S1 (lowest energy struc-
tures) and S2 (transition state structures) in the Sup-
-
As primary attack of OOH on the carbon atom of the
8
+
porting Information. We noted earlier, and have con-
cyano group in CMA is not very probable, for the reasons
firmed in our present calculations, that the activation
mentioned above, we do not think that the pathway
initiated by this process contributes to the overall pro-
cesses by which MA* is formed.
-
-
+
barriers to the addition of OOH or OH to CMA , 3 and
, as well as the hydrogen abstraction reactions are
7
+
-
negligible. Such processes are thus not rate-determining
steps, and we have not mentioned the activation barriers
to them in Table 2. The thermodynamic and kinetic
characteristics set out in Tables 1 and 2 allow one to
conclude that pathways one and two mentioned above
Beh a vior of CMA in Alk a lin e Med ia . OH , like
-
OOH , can attack carbon atom (9) or carbon atom (15).
-
The addition of OH to C(9), more probable for the
reasons mentioned above, leads to 7 (step IV), which, via
the elimination of HCN could be converted to MA (step
XXI). Step IV is highly and step XXI slightly exothermic
(Table 1), which would make this pathway probable if
not for the relatively high activation barrier to the latter
step (Table 2). In this situation we considered two other
+
are the most probable routes by which CMA is converted
to MA* in alkaline media, while pathway four seems the
most likely route by which the cation is oxidized by
hydrogen peroxide in weakly acidic and neutral media.
-
+
The OOH anions required for the process are available
pathways of the nonradiative conversion of CMA to MA
in small quantities under the latter conditions, since
H O exhibits the properties of a weak acid. On con-
2 2
in alkaline solutions: one involving steps IV, XIX, and
XX and the other steps IV, XXII, and XXIII. The overall
changes in the thermodynamic functions for both of these
pathways are comparable and favor the conversion of 1
to 16. Furthermore, the activation barrier to step XX is
4
5
sidering these pathways, we were unable to find the
structure of intermediate 13 by the DFT method; nev-
ertheless, at this level we did locate the transition state
structure for the direct conversion of 11 to 10-methyl-9-
acridinone. Which of the pathways - one or two - is more
probable is difficult to say: both are thermodynamically
equally probable, although kinetics favors pathway one.
The fact that the activation barrier to step VII is very
high probably excludes pathway three as the one respon-
sible for long-lasting chemiluminescence in weakly acidic
or alkaline media. Nevertheless, as weak chemilumines-
cence in such conditions is observed, we think that this
may have its origins in step XV, which has to overcome
a lower activation barrier than does step VII. (We were
able to locate the transition state only for the elimination
+
moderate (Table 2), which means that CMA is most
probably converted to MA via the initial abstraction of a
-
proton by OH from the OH group of intermediate 7 and
-
the subsequent elimination of CN (this pathway ac-
counts for the results shown in Figure 6). This pathway
is similar to pathway one, which describes the oxidation
+
-
of CMA with OOH , accompanied by chemilumines-
cence. Comparison of the activation barriers to step IX
or XII and XX shows, however, that they are generally
higher in the latter case, i.e., the nonradiative conversion
+
of CMA to MA in alkaline media (the reverse tendency
is noted only in the case of values relevant to the PM3-
J . Org. Chem, Vol. 69, No. 5, 2004 1613

Wr o´ blewska et al.
(
COSMO) level). This explains the mechanism by which
due to the moderate activation barriers to the rate
determining steps. It can be seen from both experiment
and calculations that CMA is stable in acidic media and
+
chemiluminescence is generated in the reaction of CMA
with OOH in alkaline media, as well as the relatively
-
+
fast conversion of the cation to MA in the absence of
hydrogen peroxide in the system.
converts relatively easily to MA in strongly alkaline
media. On the other hand, a moderately basic medium
is required to initiate efficient chemiluminescence in the
reaction of CMA with OOH . It is thus important to
select the appropriate conditions for the analytical pro-
cedures. Basic information on how this can be done is
provided by Figures 3 and 4. They demonstrate that the
total integral intensity of emission is mainly influenced
For the above reasons, neither 8 nor 9 are likely
precursors of MA. We did, however, consider pathways
V, VI, and XXIV, to complete the picture of possible
+
-
+
-
reactions of CMA with OH .
The lowest energy and transition-state structures
containing an acridine moiety occurring in all the steps
indicated in Schemes 1 and 2 are depicted in the
Supporting Information (Figures S1 and S2). However,
intermediate and transition-state molecules could not be
found for all of them at both levels of theory. The values
in Tables 1 and 2, as well as the structures in Figures
S1 and S2 (in the Supporting Information) correspond
to the steps which we have been able to locate by carrying
out geometry optimizations.
2 2
by pH and the H O concentration. As mentioned above,
an increase in pH initially gives rise to greater quantities
-
of OOH , which are necessary to initiate the processes
leading to formation of MA*, but higher pH values
+
facilitate conversion of CMA to MA. On the other hand,
-
-
2 2
both OH and OOH (or H O ) can quench MA* and
bring about its nonradiative deactivation. The emission
intensities shown in Figures 3 and 4 are thus the result
of both chemical processes (depicted in Scheme 1) and
physical processes, which are not included in the mech-
anism we have suggested. More on the analytical utility
4
. Con clu d in g Rem a r k s
+
CMA reacts with hydrogen peroxide in weakly acidic,
+
of CMA will be found in a recent publication of ours,
neutral and alkaline media producing MA*, which emits
radiation. The processes leading to chemiluminescence
which demonstrates its possible uses for determining N-,
45
O-, and S-containing nucleophiles.
-
in alkaline media are initiated by the attack of OOH
The present work is an example of the successful use
of theory to explain experimental facts. It has been shown
that experimental findings are rationally described by
the results of calculations, and the suggested mechanism
forms a convenient basis on which to consider the
chemiluminogenic features of the analytically useful
reagent, the 9-cyano-10-methylacridinium cation. The
investigations undertaken thus open up prospects for the
widespread application of this compound.
+
on carbon atom (9) of CMA , followed by the abstraction
of a proton by OH from the OOH group or, less probably,
by the addition of OH to the carbon atom of the cyano
group of 3 and the subsequent elimination of OCN and
-
-
-
2
H O. Thus, short-lived chemiluminescence (in alkaline
media) is generated via pathways involving steps I, VIII,
and XII* or, to some extent, I, XIII, and XIV*. By
contrast, long-lasting chemiluminescence (in weakly
acidic and neutral media) is most probably generated via
the pathway involving step XV*, i.e., via the direct
elimination of OCNH from intermediate 3.
Ack n ow led gm en t. The financial support of this
work from the Polish State Committee for Scientific
Research (KBN) through Grant No. 7 T09A 131 20
(Contract No. PB 1243/T09/2001/20) is gratefully ac-
knowledged.
In alkaline media and in the absence of hydrogen
+
peroxide, CMA is most probably converted to MA via
-
the addition of OH to its carbon atom (9), followed by
-
the abstraction of a proton by OH from the OH group
Su p p or tin g In for m a tion Ava ila ble: Geometries of all
stationary points and transition states in both Cartesian
coordinates and diagrammatic form, the energies of stationary
points, zero-point energies, and the number of imaginary
frequencies for transition states. This material is available free
of charge via the Internet at http://pubs.acs.org.
-
of 7 and the subsequent elimination of CN (steps IV,
XIX, and XX).
The conversion of CMA+ to MA* in the presence of
hydrogen peroxide creates a basis for its analytical use.
+
CMA is a very promising chemiluminogen since it reacts
-
relatively easily with OOH in alkaline media. This is
J O0354387
1
614 J . Org. Chem., Vol. 69, No. 5, 2004