J. Phys. Chem. 1082, 86,5227-5230
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Effects of Excited-State Prototropic Equilibria on the Fluorescence Energies of Benzimidazole and Thiabendazole Homologues Patrlcla C. Tway‘ and L. J. Cllne Love. Department of Chemistty, Seton Hall University, South Orange, New Jersey 07079 (Received: August 31, 1982)
Excited-state prototropic equilibria are proposed to explain the appearance of new charge transfer bands in the fluorescence spectra of certain benzimidazole and thiabendazole homologues. The effects of pH on fluorescence energies and intensities, proton NMR data, low-temperature luminescence studies, and pK, values are used to support the postulated mechanisms. The 5-amino derivatives are believed to undergo excited-state deprotonation, while the 5-hydroxy derivative forms an excited-state zwitterion.
Introduction In the previous paper we described the luminescence properties of benzimidazole, thiabendazole, and ten of their derivatives as a function of solvent and the side-chain substituents on the molecule.2 It wm proposed that these benzimidazole homologues upon absorption of radiation are excited to a manifold of singlet states; either the ?r H* or the charge transfer state predominate depending on the side-chain substituent and solvent system. Generally, in more polar solvents and in solutes with strong electron-donating substituents at the 5 position, the charge transfer transition is stabilized relative to the H ?r* transition. Anomalously large shifts of the fluorescence transition which cannot be explained by solvent polarity, however, were seen for 5-hydroxythiabendazole,&aminothiabendazole, and 5-aminobenzimidazole in dilute acid solution. The luminescence properties of these compounds in aqueous acid solution is the subject of this paper, and transition mechanisms to explain these properties are proposed.
-
-
Experimental Section The benzimidazole and thiabendazole analogues studied were obtained from the sample collection of Merck & Co., Inc., Rahway, NJ, and were better than 98% pure. The analogues differed from the parents with substituents at the 5 position (R,) on the homocyclic ring and at the 1 position (R,) on the pyrrole nitrogen. The species studied included benzimidazole (R, = H, R2 = H), 5-aminobenzimidazole (R, = NH2, R2 = H), thiabendazole (R, = H, & = H), 5-aminothiabendazole (R, = NH2, R2 = H) 5hydroxythiabendazole (R, = OH, R2 = H), &(dimethylamino)thiabendazole (R, = (CH,),N, R2 = H), N1methylthiabendazole (R, = H, R2 = CHJ, and cambendazole (R, = NHCOOCH(CH3)2,R2 = H). All organic solvents were Burdick & Jackson “distilled in glass”, and all aqueous solutions were made with doubly distilled water. Solutions were prepared to be lo5M or less to avoid concentrational quenching. The fluorescence of these compounds was found to be insensitive to oxygen quenching and the solutions were not deaerated. The instrumentation used to measure absorption, fluorescence and phosphorescence energies, lifetimes, and quantum yields was described previously.2 The molar extinction coefficient of a compound was assumed to be (1)Merck and Co., Rahway, NJ 07065. (2) Tway, P. C.; Cline Love, L. J. J.Phys. Chem., preceding paper in this issue. 0022-3654/82/2086-5227$01.25/0
TABLE I: Fluorescence Energy Maxima of Benzimidazole and Thiabendazole Analogues in Polar S o l v e n t 8
compd
EtOH
MeOH
0.1 N HC1
benzimidazole 5-aminobenzimidazole thiabendazole 5-hydroxy thiabendazole 5-aminothiabendazole cambendazole
291 358 350
291, 299 358 346 400 464 398
360 444 354 54 0 520 44 0
388 457 385
All wavelengths listed in nm, maxima.
t2
nm.
Wavelength
independent of temperature for quantum yield calculations at 77 K.2 The NMR spectra of thiabendazole in CD30D and CD30D with CF3C02Hwere run using a Varian HA-100 for ‘H NMR.
Results Fluorescence Properties. The absorption (A,) and fluorescence (Af) wavelength maxima of the compounds were measured as a function of solvent. The absorption wavelength maxima were found to be relatively insensitive to solvent; however, the fluorescence transition energies, given in Table I, generally shift to longer wavelengths as the solvent is made more polar. Anomalously large shifts of the fluorescence transition which cannot be explained by solvent polarity are seen for 5-hydroxythiabendazole, 5-aminothiabendazole, and 5aminobenzimidazole in acid solution (Table I). Such large Stokes shifts (AA = Af - A, = 180-220 nm) cannot be explained simply on the basis of solvent polarity but rather indicate a possible change in structure of the excited state of these compounds in acid solution. To obtain a better understanding of the effects of pH on the luminescence spectra of these compounds, we measured the absorption and fluorescence spectra of thiabendazole, 5-hydroxythiabendazole, 5-aminothiabendazole, and cambendazole in several different acid solutions. The absorption spectra of these compounds shift only slightly (less than 15 nm) and the extinction coefficients do not change as a function of acid strength. The fluorescence data, presented in Table 11, show that the fluorescence transition of thiabendazole and cambendazole are only slightly affected by pH, but the fluorescence spectra of 5-hydroxythiabendazole and 5-aminothiabendazole are strongly pH dependent. In strong acid solutions both of these compounds have a 0 1982 American Chemical Society
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The Journal of Physical Chemistry, Vol. 86,No. 26, 1982
Tway and Cline Love
TABLE 11: Fluorescence Wavelength Maxima as a Function of Solvent pH wavelength maxima, nm compd thiabendazole cam bendazole 5-aminothiabendazole 5-hydroxythiabendazole a
2.4 N HC1
1.2 N HC1
0.12 N HC1
0.01 NHCI
1.0 NH,SO,
351 430 34 1
352 43 1 350, 503
351 431 508 432, 529
349 435 508 5 29
353 43 1 510 428, 520
a
a
a a
353 411
a
U
U
402
Quenched.
TABLE 111: pK, Values of Benzimidazole and Thiabendazole and Some Analogues
PK,'
compd benzimidazole thiabendazole 5-aminothiabendazole 5-(dimethy1amino)thiabendazole cambendazole ,VI-methylthiabendazole 5-hydroxy thiabendazole a
1.0 buffer NNaOH pH7.6
5.48 -0.5, 4.8, 1 1 . 3 3.0, 5.2, 1 0 . 5 2.6, 5.7, 10.3 - 0 . 5 , 4.8, 10.8 -0.5, 4.6 0.5, 4.7, 10.3
-
Reference 4 , i 0 . 2
relatively high energy fluorescence transition (Bhydroxythiabendazole, Xf = 430 nm; 5-aminothiabendazole, Xf = 341 nm) similar to that seen in cambendazole and thiabendazole, respectively. In more dilute acid solutions, however, the fluorescence transitions of the amino- and hydroxy-substituted species shift to very low energies (Af = 510-530 nm). These results suggest that the equilibrium excited state species, not the ground state or Franck-Condon excitedstate species, change as a function of solvent acidity. In order to determine if the equilibrium excited state species of the amino- and the hydroxy-substituted compounds are structurally different from the Franck-Condon excitedstate species, we measured the fluorescence spectra of 5-hydroxythiabendazole, 5-aminothiabendazole, 5-aminobenzimidazole, and cambendazole in 0.1 N HCl a t 77 K, where it is assumed that no structural rearrangement of the excited state species can occur. At 77 K, 5-hydroxythiabendazole fluoresces a t 458 nm (529 nm at 25 "C), 5-aminothiabendazole at 342 nm (508 nm a t 25 "C), and 5-aminobenzimidazoleat 286 nm (444 nm a t 25 "C);these transitions at 77 K are similar in energy to the transitions for these compounds in strong acid at room temperature (Table 11). The fluorescence spectrum of cambendazole at 77 K, which was measured as a control, shows very little shift with temperature (428 nm at 77 K; 440 nm at 25 "C). These results at room temperature and a t 77 K indicate that the large shifts in the fluorescence energy of certain compounds in dilute acid are a result of pH-dependent equilibria involving the excited-state species. pK, and pK,* Studies. Because of the unusual behavior of these compounds in acid, it was important to examine the pK, and the pK,* of the molecules. The pKa* is the dissociation constant of the excited conjugate acid and can be very different from the pK, of the ground-state acid because of the differences in the electronic distribution between the two states. The pK,'s of some of these compounds were determined by potentiometric and spectrophotometric titrations, and are presented in Table III.4 From its liquid-liquid distribution properties, thiaben(3) Parker, C. A. "Photoluminescence of Solutions with Applications to Photochemistry and Analytical Chemistry"; Elsevier: Amsterdam, 1968; pp 261-8. (4) The pK, values were determined by G. B. Smith, Merck & Co., Rahway, NJ.
dazole is known to exist in pH 7 solution as a neutral molecule. Thus, the pK, value of 11.3 reflects loss of the proton on the nitrogen in the indole ring to form an anion. N,-Methylthiabendazole has no similar pK, value, as expected. Most of the compounds form cations in the pH range of 4.5-5.5, while 5-aminothiabendazole forms a dication (protonation of the amino group) at pH values below 3.0. Although pK,* values would be helpful in interpretation of these species photophysical properties, such values could not be obtained because the fluorescence lifetimes are very short. This prevents the use of the fluorometric titration technique5 and, the fact that the ground and the excited-state species are probably different in some compounds, eliminates Forster cycle calculations? So that these pK, values could be used to explain the effects of pH on the luminescence properties of these molecules, it was necessary to determine the site of protonation forming the monocation, since either the nitrogen on the thienyl ring or the nitrogen on the imidazole ring can be protonated. From the literature the pK, of thiazole is 2.5, that of 4-methylthiazole is 2.9, and that of benzimidazole4,' is 5.5. These data demonstrate that either nitrogen can be protonated, although the one on the imidazole ring is slightly easier to protonate. Proton NMR data confirmed that thiabendazole is protonated on the imidazole ring in acid solutions. The site most affected by the protonation of thiabendazole is the proton on the 4-position carbon of the thienyl ring, with a downfield shift from 8.32 to 8.76 ppm. Protonation of the imidazole ring permits one to draw a resonance structure (I) which decreases shielding at that proton
d)a-J HI
S
I
group. An analogous resonance structure cannot be drawn if protonation occurs on the thienyl ring. When protonated, the imidazole ring protons in thiabendazole are similar in their NMR spectra to the imidazole ring protons of protonated benzimidazole, which provides added confirmation that protonation occurs on the imidazole ring in thiabendazole as it does in benzimidazole. Protonation of the thienyl ring to form a dictation does occur at a very low pH (pK, = -0.5). The pK, and the NMR data show that these compounds in their ground state exist as a cation protonated on the imidazole ring at pH values below 5, as a neutral molecule in the pH range 5-11, and as an anion at pH values greater (5) Schulman, S. G.; Capomacchia, A. C. J. Phys. Chem. 1975, 79, 1337-43. (6) Schulman, S. G.; Fernando, Q. Tetrahedron 1968, 24, 1777-83. (7) "The Merck Index"; Merck & Co.: Rahway, NJ; 8th ed, 1976.
The Journal of Physical Chemistty, Vol. 86,No. 26, 1982 5229
Fluorescence Spectra of Benzimidazole Analogues
than 11. The only exceptions are 5-aminothiabendazole and 5-aminobenzimidazole,which exist as dications below pH 3.
Discussion Previous work has shown that upon absorption of radiation benzimidazole, thiabendazole, and several homologues are excited to a manifold of singlet states; one excited state has a x* character while the other has charge transfer characteristics. Which excited state(s) are appreciably populated depend on both molecular and environmental factors. Generally, in more polar solvents and in solutes with strong electron-donating substituents at the 5 position, the charge transfer transition is stabilized relative to the a a* transition. Thus 5-hydroxythiabendazole undergoes a charge transfer transition in ethanol, while thiabendazole in most solvents has a x x* transition. As has been seen, the exceptionally large shifts in the fluorescence energies to longer wavelength of 5-hydroxythiabendazole, 5-aminothiabendazole, and 5aminobenzimidazolein 0.1 M HC1 cannot be explained as a simple solvent polarity effect. However, the behavior of these compounds can be rationalized from the data in Tables I1 and 111. The 5-aminothiabendazole derivative (11)exists in acid
-
-
-
Y @NH3QN
)-q
I
H
I1
solution as a dication in the ground state. In strong acid solution (2.4 N HC1) the 5-amino group is protonated both in the ground and the excited states; it has no available nonbonding electrons, it is not electron donating, and the fluorescence spectrum is essentially the same as that of thiabendazole in acid (A, = 341 nm vs. 351 nm of the parent). The NH3+substituent shifts the band to a slightly shorter wavelength because of the inductive effect on the electron distribution in the aromatic ring. In dilute acid solutions, however, the 5-aminothiabendazole 341-nm transition decreases in intensity with a concomitant appearance of a second fluorescence transition at 500-510 nm. In the excited state the 5-amino group and the pyrrole nitrogen at the 1 position become more acidic, while the pyridinic nitrogen at the 8 position becomes more basic. It is proposed that in dilute acid solutions the molecule is a dication in the ground state, but a monocation in the excited state. Because the 5-amino group becomes more acidic while the %nitrogen becomes more basic in the excited state: a proton is lost from the amino group after excitation. The excited-state monocation is then strongly stabilized relative to the ground state by charge transfer from the nonbonding electrons on the amino group to the ring system causing a large shift to longer wavelength in the fluorescence spectrum. Similar results are seen in the fluorescence spectrum of 5-aminobenzimidazole. Excited-state deprotonation can also be invoked to rationalize the data for 5-hydroxythiabendazole. I t undergoes a charge transfer transition at 400 nm in methanol, pH 7 buffer, and in strong acid solution, similar to the transition seen with cambendazole. However, upon decreasing the acid strength to 1.0 N a second fluorescence (8! Schulman, S. G. in “Physical Methods in Heterocyclic Chemistry”; Katntzky, A. R., Ed.; Academic Press: New York, 1974; Vol. VI, p 147-97.
H
ti
GROUND S T A T E
t1 H
H
EXCITED S T A T E
i
1
Flgure 1. The ground- and excited-state structures proposed for 5hydroxythiabendazole in 0.1 N and 0.01 N HCI solutions.
transition at 520-530 nm appears which increases in intensity as the acidity is further decreased to 0.01 N. 5Hydroxythiabendazole in the ground state exists as a cation in both 1 and 0.01 N acid solution. It is postulated that in dilute acid solutions the excited-state species is a zwitterion which is strongly resonance stabilized, as shown in Figure 1,and this stabilization produces the large shift to longer wavelength in the fluorescence band. The formation of a zwitterion species is known to occur in the excited state of 8-hydroxyquinoline.8 This proposed excited-state zwitterion mechanism is supported both by data from the literature and low-temperature experiments. It is known that the pKa and pKa* of phenol and a-naphthol are 10 and 5.7,’O and 9.2 and 2.0,” respectively. a-Naphthol is a much stronger acid than phenol in the excited state because of the large aromatic ring system which stabilizes anion formation. By analogy, 5-hydroxythiabendazolehas a large aromatic ring system and the pK,* for the 5-hydroxy group could reasonably be in the 2-3 range. On the other hand, the 8nitrogen in benzimidazole has a pK, value of 4.5 and a pK,* of 10.8 for cation formation.l* Clearly, the &nitrogen on the imidazole ring is a much stronger base than the 5-hydroxy group in the excited state, and it is highly probable that the pKa* of the 5-hydroxy group is small enough that zwitterion formation occurs in dilute acid solutions. Additional support is given by the fluorescence spectra of these compounds in 0.1 N HC1 at 77 K, which are very similar to their fluorescence spectra in concentrated acid solutions at room temperature. A t 77 K the molecules are unable to lose a proton in the excited state to form a zwitterion so that the “normal” charge transfer transition occurs.
Summary A second type of charge transfer transition can occcur in benzimidazole and thiabendazole analogues with strong (9) Ballard, R. E.;Edwards, J. W. J. Chem. SOC.1964, 4868-74. (10) Bartok, W.; Lucchesi, P. J.; Snider, N. S. J.Am. Chem. SOC.1962, 84,1842-4. (11) Parker, C. A. “Photoluminescence of Solutions with Applications to Photochemistry and Analytical Chemistry”; Elseview: Amsterdam, 1968; p 333. (12)Longworth, J. W.; Rahn, R. 0.;Shulman, R. G. J. Chem. Phys. 1966, 45, 2930.
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J. Phys. Chem. 1982,86,5230-5234
electron-donating substituents dissolved in dilute acid. This new charge transfer transition is attributed to loss of a proton in the excited-state species producing a fluorescent monocation (in the case of 5-amho derivatives) or a zwitterion (in the case of 5-hydroxy derivatives). These characterizations are supported by pK, studies,
NMR results, and low-temperature comparisons.
Acknowledgment. We thank Jerry A. Hirsch for helpful comments on the data, and Alan W. Douglas, Merck, Inc., Rahway, NJ, for providing the NMR data. P.C.T. also thanks Merck, Inc. for partial financial support.
Kinetic Studies on Protonation-Deprotonation of Phosphate Groups and Proton Intercalation-Deintercalation in CY- and y-Zirconium Phosphates Using the Pressure-Jump Technique Mlnoru Sasakl, Naokl Mlkaml, Tetsuya Ikeda, Kazuakl Hachlya, and Tatsuya Yasunaga Department of Chemistry, Faculy of Science, Hiroshima Universify, Hiroshima 730, Japan (Received: May 19, 1982; I n Final Form: July 20, 1982)
In aqueous suspensions of a- and y-zirconium phosphates, two relaxations of the order of milliseconds and seconds were observed by using the pressure-jump technique with conductivity detection. In both suspensions, the fast relaxation time decreases with particle concentration,and the slow one decreases and then approaches a constant value. The dependence of pH on the particle concentrationin the zirconium phosphate suspensions revealed that the degree of dissociation of phosphate groups existing in layers and on the surface of zirconium phosphates decreases with increasing concentration of protons released. Taking into account the surface potential created by the negatively charged phosphate groups, the fast and slow relaxations were attributed to protonation-deprotonation of the phosphate groups on the surface and intercalation-deintercalation of protons in the interlayer of the a- and y-zirconium phosphates, respectively. The equilibrium constants of the protonation-deprotonation determined kinetically were in agreement with the acidity constant of phosphoric acid in homogeneous solution. The purpose of the present investigation is to elucidate Introduction kinetically the protonation of the phosphate groups and Layered intercalation compounds, in which adjacent intercalation of protons in a- and y-zirconium phosphates layers are held together primarily by van der Waals forces, by using the pressure-jump technique with conductivity are known to have host lattice sites for guest species, and detection. their physical properties are modified significantly by topotactic bulk reaction processes involving intercalation of Experimental Section the guest species.*-7 In particular, insoluble polybasic acid The pressure-jump apparatus used is the same as that salts of tetravalent metals exhibit the interesting property reported previously,12and the time constant of the pressure that free protons resulting from protonation of polybasic jump is 80 ps. acid groups in the layers are exchangeable selectively for a- and y-Zirconium phosphates Zr(HP04)2.H20and certain cations through the intercalation p r o c e s ~ . ~The ~ ~ ~ ~ *Zr(HP04)2.2H20, ~ respectively, were supplied by Dr. S. study of intercalation dynamics is necessary to attain a Yamanaka of the Faculty of Engineering of Hiroshima fundamental understanding of the nature of the selectivity University. The X-ray powder diffraction patterns of both in the cation intercalation. However, the usual intercasamples were the same as those reported1 and verified that lation process into the compounds is too fast to be observed both samples are not amorphous but layered structures. by ordinary methods. The size, shape, and uniformity of the particles of zircoVery recently, using the relaxation techniques such as nium phosphate were examined by using a scanning the pressure-jump method, we have performed kinetic electron microscope, and the micrographs are shown in studies on rapid reactions a t solid-liquid interfaces and Figures 1, a and b. As can be seen from this figure both in the micropores of solids, and many important kinetic crystal forms were plates, especially well-grown ribbonlike insights into these reactions have been obtained.'@15 ones in the y-zirconium phosphate. The particle sizes were (11) R. D. Astumian, M. Sasaki, T. Yasunaga, and 2. A. Schelly, J . (1) A. Clearfield and J. A. Stynes, J . Inorg. Nucl. Chem., 26, 117 (1964). ~_._.,. (2) R. Schollhorn, R. Kuhlmann, and J. 0. Besenhard, Mater. Res. Bull., 11, 83 (1976). (3) S. Yamanaka, Y. Horibe, and M. Tanaka, J. Znorg. Nucl. Chem., 38, 323 (1976). (4) S. Miyata and T. Hirose, Clays Clay Miner., 26, 441 (1978). (5) R. Schollhorn, Physica, 99B, 89 (1980). (6) P. Calombet and M. Danot, Physica, 99B, 117 (1980). (7) T. Hibma, Phrsica. 99B. 136 (1980). (8) G . Alberti, A&. Chem. Res., 11, 163 (1978). (9) S. Son, F. Kanamaru, and M. Koizumi, Inorg. Chem., 18, 400 (1979). (10) M. Ashida, M. Sasaki, H. Kan, T. Yasunaga, K. Hachiya, and T. Inoue, J . Colloid Interface Sci., 67, 219 (1978).
Phys. Chem., 85, 3832 (1981). (12) K. Hachiya, M. Ashida, M. Sasaki, H. Ken, T. Inoue, and T. Yasunaga, J. Phys. Chem., 83, 1866 (1979). (13) K. Hachiya, J. Sci. Hiroshima Uniu., Ser. A: Phys. Chem., 45, 157 (1981). (14) T. Ikeda, J. Nakahara, M. Sasaki, and T. Yasunaga, J . Phys.
Chem., submitted for publication. (15) M. Sasaki, N. Mikami, T. Ikeda, K. Hachiya, and T. Yasunaga, J. Phys. Chem., in press. (16) J. A. Davis, R. 0. James, and J. 0. Leckie, J . Colloid Interface Sci., 63, 480 (1978). (17) S. Yamanaka and M. Tanaka, J. Inorg. Nucl. Chem., 41, 45 (1979). (18) T. Ikeda, M. Sasaki, K. Hachiya, R. D. Astumian, T. Yasunaga, and 2. A. Schelly, J. Phys. Chem., 86, 3861 (1982).
0022-3654/82/2086-5230$01.25/00 1982 American Chemical Society
