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Photoproduct Selectivity in Reactions Involving Singlet and Triplet Excited States within Bile Salt Micelles Mahesh Pattabiraman, Lakshmi S. Kaanumalle, and V. Ramamurthy* Department of Chemistry, UniVersity of Miami, Coral Gables, Florida 33124 ReceiVed October 19, 2005. In Final Form: December 7, 2005 Generally, photochemical reactions tend to give more than one product. For such reactions to be useful one should be able to control them to yield a single product. Of the many approaches used in this context, the use of reaction media with features different from those of isotropic solutions has been very effective. We provide results of our studies on four reactions within bile salt micelles (cholic acid and deoxycholic acid). These four reactions involve homolytic cleavage of a C-C or C-O bond to yield either a singlet or triplet radical pair. The bile salt micelles control the rotational and translational mobilities of the radical pair, resulting in photoproduct selectivity. The dynamic nature of the bile salt micelles results in differential effects on the singlet and triplet radical pairs.
Introduction Product selectivity in reactions is one of the most sought-after pursuits of photochemists.1 Several approaches have been devised so far in this area of research with varying degrees of success.2 One of the most successful approaches involves the use of supramolecular assemblies.3 In this context we have been pursuing methods to achieve selectivity in photoreactions carried out in aqueous media.4 In this article we present the results of our studies on the use of bile salt micelles, which are capable of solubilizing organic molecules in water, as media in achieving product selectivity in photochemical reactions. Bile salt micelles are also referred to as cholate micelles in the literature, and we use the two terms interchangeably in the paper. Ready commercial availability, environmental compatibility, and their well-known ability to solubilize organic molecules in water prompted us to examine the potential of cholate micelles as reaction media. Bile salts with steroidal skeletons are important for the solubilization of fats in the digestive system.5 The puckered * Corresponding author. Telephone: (305) 284-1534. Fax: (305) 2844571. E-mail:
[email protected]. (1) Natarajan, A.; Kaanumalle, L. S.; Ramamurthy, V. In CRC Handbook of Organic Photochemistry and Photobiology; Horspool, W., Lenci, F., Eds.; CRC Press: Boca Raton, FL, 2004; Vol. 3, p 107. (2) Kaanumalle, L. S.; Natarajan, A.; Ramamurthy, V. In Synthetic Organic Photochemistry; Griesbeck, A., Mattay, J., Eds.; Marcel Dekker: New York, 2004; Vol. 9, p 553. (3) (a) Ramamurthy, V.; Eaton, D. F. Acc. Chem. Res. 1988, 21, 300. (b) Weiss, R. G.; Ramamurthy, V.; Hammond, G. S. Acc. Chem. Res. 1993, 26, 530. (c) Ramamurthy, V.; Weiss, R. G.; Hammond, G. S. In AdVances in Photochemistry; Volman, D. H., Neckers, D., Hammond, G. S., Eds.; Wiley-Interscience: New York, 1993; Vol. 18, p 67. (d) Scaiano, J. C.; Garcia, H. Acc. Chem. Res. 1999, 32, 783. (e) Turro, N. J. Acc. Chem. Res. 2000, 33, 637. (f) Tung, C.-H.; Wu, L.-Z.; Zhang, L.-P.; Li. H.-R.; Yi, X.-Y.; Song, K.; Xu, M.; Yuan, Z.-Y.; Guan, J.-Q.; Wang, H.-W.; Ying, Y.-M.; Xu, X.-H. Pure Appl. Chem. 2000, 72, 2289. (g) Bhattacharya, K. Acc. Chem. Res. 2003, 36, 95. (h) Tung, C.-H.; Wu, L.-Z.; Zhang, L.-P.; Chen, B. Acc. Chem. Res. 2003, 36, 39. (i) Liu, R. S. H.; Hammond, G. S. Acc. Chem. Res. 2005, 38, 396. (j) Huang, C.-H.; Bassani, D. M. Eur. J. Org. Chem. 2005, 19, 4041. (4) (a) Kaanumalle, L. S.; Nithyanandhan, J.; Pattabiraman, M.; Jayaraman, N.; Ramamurthy, V. J. Am. Chem. Soc. 2004, 126, 8999. (b) Kaanumalle, L. S.; Ramesh, R.; Maddipatla, M. V. S. N.; Nithyanandhan, J.; Jayaraman, N.; Ramamurthy, V. J. Org. Chem. 2005, 70, 5062. (c) Kaanumalle, L. S.; Gibb, C. L. D.; Gibb, B. C.; Ramamurthy, V. J. Am. Chem. Soc. 2005, 127, 3674. (d) Kaanumalle, L. S.; Gibb, C. L. D.; Gibb, B. C.; Ramamurthy, V. J. Am. Chem. Soc. 2004, 126, 14366. (e) Arumugam, S.; Vutukuri, D. R.; Thayumanavan, S.; Ramamurthy, V. J. Am. Chem. Soc. 2005, 127, 13200. (f) Karthikeyan, S.; Ramamurthy, V. Tetrahedron Lett. 2005, 46, 4495. (g) Pattabiraman, M.; Natarajan, A.; Kaanumalle, L. S.; Ramamurthy, V. Org. Lett. 2005, 7, 529. (h) Pattabiraman, M.; Natarajan, A.; Kaliappan, R.; Mague, J. T.; Ramamurthy, V. Chem. Commun. 2005, 4542. (i) Kaliappan, R.; Kaanumalle, L. S.; Ramamurthy, V. Chem. Commun. 2005, 4056.
structure of bile salt molecule with a concave side houses the hydrophilic hydroxyl groups, hydrophobic methyl groups lie on the convex side, and a carboxylate group lies on top of the steroidal framework (Figure 1). These amphiphilic molecules aggregate in solution to form micelles. Unlike long chain surfactants, these ampiphiles do not have a well-defined concentration at which aggregation can occur. The critical micellar concentration (cmc) is instead believed to span a range.6 Other characteristics of bile salt aggregates such as aggregation pattern, micellar size, structure, rigidity, aggregation number, and microviscosity also differ significantly from those of conventional long chain surfactant micelles.7 Studies aimed at determining cmc, aggregation number, and size of these micelles indicate that bile salts assemble to form primary aggregates comprised of six to ten monomers in aqueous media.7,8 Aggregates are formed such that the hydrophobic moieties lining the convex surface point toward the interior of the aggregate while the hydrophilic hydroxyl groups remain exposed to the aqueous phase (Figure 2). Primary aggregates provide hydrophobic pockets where apolar guests could bind in aqueous media. Primary aggregates, at higher concentrations (>20 mM for sodium cholate and 12 mM for sodium deoxycholate), aggregate among themselves to form a secondary aggregate possessing secondary binding sites. The formation of secondary aggregates is proposed to be assisted by hydrogen bonding of the hydroxyl groups on the concave side of monomers that make up the primary aggregate.8 For sodium cholate (NaCh) primary aggregates form at a concentration range of 7-20 mM in 0.2 M aqueous NaCl and are predominantly composed of six to ten monomeric units.9 For sodium deoxycholate (NaDCh) (5) (a) Xiaohong, C.; David, G. J. W.; Wiedmann, S.; Timothy, S. J. Pharmcol. Sci. 1997, 86, 372. (b) Beckerdite, J. M.; Adams, E. T. Biophys. Chem. 1985, 21, 103. (c) Hofmann, A. F. Biochem. J. 1963, 89, 57. (6) (a) Mukerjee, P.; Moroi, Y.; Murata, M.; Yang, A. Y. S. Hepatology 1984, 4, 61. (b) Mukerjee, P.; Cardinal, J. R. J. Pharm. Sci. 1976, 65, 882. (c) Ekwall, P. J. Colloid Sci. 1954, (Suppl. 1), 66. (7) (a) Small, D. M. In The Bile Salts; Nair, P. P., Kritchevsky, D., Eds.; Plenum Press: New York, 1971; Vol. 1, p 249. (b) Li, G.; McGown, L. B. J. Phys. Chem. 1993, 97, 6745. (8) (a) Esposito, G.; Giglio, E.; Pavel, N. V.; Zanobi, A. J. Phys. Chem. 1987, 91, 356. (b) O’Connor, C. J.; Wallace, R. G. AdV. Colloid Interface Sci. 1985, 22, 1. (c) Shurtenberger, P.; Mazer, N.; Kanzig, W. J. Phys. Chem. 1983, 87, 308. (d) Small, D. M.; Penkett, S. A.; Chapman, D. Biochim. Biophys. Acta 1969, 176, 178. (9) (a) Meyerhoffer, S. M.; McGown, L. B. Anal. Chem. 1991, 63, 2082. (b) Zana, R.; Guveli, D. J. Phys. Chem. 1985, 89, 1687. (c) Lindman, B.; Kamenka, N.; Fabre, H.; Uimus, J.; Weiloch, T. J. Colloid Interface Sci. 1980, 556.
10.1021/la0528192 CCC: $33.50 © 2006 American Chemical Society Published on Web 01/12/2006
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Figure 1. Structure of bile salts and conventional micellar units.
Figure 2. Cartoon representation of bile salt micelles.11 Aggregation numbers of the micelle are not known. “O” in the bile salt monomer structure represents hydrophilic groups OH or COOH.
primary aggregates in water are known to start forming at concentrations as low as 7-9 mM. The dynamics and accessibility of guests bound to primary and secondary aggregates have been shown to be different by Bohne et al.10a-e Motivated by the known ability of bile salts to solubilize hydrophobic molecules in water, we have explored the use of bile salts as media for conducting photochemical reactions. In this article we present the results of photochemical studies performed with naphthyl benzoate (3) (Scheme 1), 1-naphthyl (10) (a) Rinco, O.; Christine, N. M.; Ovans, R.; Bohne, C. Photochem. Photobiol. 2003, 2, 1140. (b) Rinco, O.; Kleinman, M. H.; Bohne, C. Langmuir 2001, 17, 5781. (c) Li, Y.; Holzwarth, J. F.; Bohne, C. Langmuir 2000, 16, 2038. (d) Ju, C.; Bohne, C. Photochem. Photobiol. 1996, 63, 60. (e) Ju, C.; Bohne, C. J. Phys. Chem. 1996, 100, 3847. (f) Gouin, S.; Zhu, X. X. Langmuir 1998, 14, 4025.
phenylacyl ester (8) (Scheme 2), 1-phenyl-3-p-tolyl-propan-2one (17) (Scheme 3), and benzoin ethyl ether (24) (Scheme 4) included within the aggregates of NaCh and NaDCh micelles.
Results and Discussion Use of micelles of bile salts to carry out photoreactions requires the knowledge of the location of reactants. We conducted 1H NMR studies of guest molecules within NaCh and NaDCh micelles to gain an understanding of the reactant’s positioning. Of the four guests (3, 8, 17, and 24) investigated, only benzoin ethyl ether (24) was soluble enough in water to record a NMR spectrum. Hence, 1H NMR titration studies could be performed with this molecule only.
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Langmuir, Vol. 22, No. 5, 2006 2187 Scheme 1
Scheme 2
Inclusion of Benzoin Ethyl Ether (24) within Cholate and Deoxycholate Micelles: NMR Studies. 1H NMR spectra of 24 in water in the presence and absence of NaCh and NaDCh are presented in Figure 3. Addition of 20 mM NaCh (at which concentration the primary binding sites predominate) had differential effects on the various protons of the guest, causing the Hc proton of 24 to undergo an upfield shift of 0.65 ppm and the aromatic protons to be shifted slightly downfield (∼0.1 ppm). No significant changes of the host protons were observed. A plot of the change in the chemical shift of Hc proton in 0.2 M NaCl in D2O (change in ppm) against NaCh concentration is shown in Figure 4. NaCh concentration causes a steady increase in chemical shift until 20 mM and reaches a saturation point at ∼30 mM. Changes in the proton signals of the guest indicate its inclusion within the micellar assembly, probably within the primary binding site. A small shift observed in the NMR spectra for the Hc proton of benzoin ethyl ether even at 3 mM concentration of NaCh is most likely due to aggregation of NaCh monomer units even at such low concentration. This observation is consistent with the polarity probe measurements reported by Bohne, Guin, and their co-workers.10d,f While the factors for the guest proton
shift are not clear, we speculate that the polarity differences between the aqueous bulk and bile salt interior have a role. Deoxycholate aggregates caused slightly more changes in chemical shifts of both Ha and Hc signals than cholate aggregates (Figure 3 bottom). As expected, NaDCh micelles showed saturation of NMR shift at lower concentration than NaCh micelles (Figure 3). Photochemical Reactions Conducted within Cholate and Deoxycholate Micelles. The photochemical reactions within cholate and deoxycholate micelles were conducted with the four compounds 3, 8, 17, and 24. The photochemical reactants we have used could be classified into two categories based on the excited state from which they react. Naphthyl benzoate (3) and 1-naphthyl phenylacyl ester (8) yield their corresponding photoproducts from their singlet excited states. 1-Phenyl-3-ptolyl-propan-2-one (17) and benzoin ethyl ether (24) react from their triplet excited states. As mentioned above, based on the 1H NMR titration of 24 with NaCh and NaDCh micelles, we assume that the product distribution from the excited state species of all four reactants is predominantly governed by the primary binding site of bile salt aggregates.
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Scheme 4
Photo-Fries Rearrangement of Naphthyl Benzoate Solubilized in Cholate and Deoxycholate Micelles. Photo-Fries reaction of naphthyl benzoate (3) is known to proceed predominantly via an excited singlet state (Scheme 1) from which homolytic O-CO bond cleavage leads to the formation of the radical pair A.12 The radical pair, trapped in a solvent cage, may intramolecularly rearrange to yield 2-benzoyl-1-naphthol (4) and (11) Small, D. M. AdV. Chem. Ser. 1968, 84, 31. (12) (a) Pitchumani, K.; Warrier, M.; Cui, C.; Weiss, R. G.; Ramamurthy, V. Tetrahedron Lett. 1996, 37, 6251. (b) Miranda, M. A. In CRC Handbook of Photochemistry and Photobiology; Horspool, W. M., Song, P. S.; Eds.; CRC Press: Boca Raton, 1995; p 570. (c) Cui, C.; Weiss, R. G. J. Am. Chem. Soc. 1993, 115, 9820.
4-benzoyl-1-naphthol (5) or escape from the solvent cage to yield benzil (6) and 1-naphthol (7). In homogeneous media the distribution of the rearrangement products is proportional to the electron densities at the respective positions in the aryl ring. In confined media, in addition to these factors, rotational and translational restrictions on the radical pair also play a role in product distribution. Irradiation of 3 in hexane, an isotropic medium that represents the behavior of a guest in unrestricted environment, resulted in the formation of 62% 4 and 24% 5 (Table 1). Small amounts of cage escape products (6 and 7) were also observed. Irradiation of compound 3 included within cholate and deoxycholate micelles
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Figure 3. 1H NMR spectra of benzoin ethyl ether (24) in D2O (top), inclusion complex within NaCh micelle (middle), and NaDCh micelles (bottom). Concentration of the guest (24), 1.4 mM; concentration of NaCh, 32 mM (middle); concentration of NaDCh, 14 mM (bottom).
Figure 4. Plot of shift in Hc chemical shift of benzoin ethyl ether vs concentration of sodium cholate.
in aqueous solutions showed a marked difference in behavior compared to that in hexane (Table 1). Irradiation of 3 solubilized by NaDCh micelles at 12 mM concentration resulted in the exclusive formation of 4 and the complete suppression of products arising from cage escape. Similar irradiation of the guest included in NaCh micelles at 21 mM concentration of the host also showed a considerable differ-
ence in photoproduct distribution, although the selectivity in formation of 4 was not as high as in NaDCh micelles (Table 1). Results presented above clearly demonstrate that the singlet radical pair A generated in the interstices of the primary aggregates is restrained within the cage, eliminating all cage escape products (6 and 7). Another important aspect, namely the higher ratio of products 4:5 in the cholate and deoxycholate aggregates than in
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Table 1. Product Selectivity Achieved in the Photochemistry of Naphthyl Benzoate (3) Incorporated in Bile Salt Micelles and Other Mediaa medium
4
5
6
7
ratio 4:5
hexaneb NaDChb NaChb SDSb CTAC SDO
62 99 85 83 87 75
24 1 15 17 12 21
10
4
1:0.39 1:0.01 1:0.18 1:0.20 1:0.14 1:0.28
1 3
1
The numbers reported are average of at least five independent runs, error limit (5%. Concentration of 3 in hexane, 10-3 M. Concentrations of micellar solutions: NaCh, 20 mM; NaDCh, 12 mM;SDS, 20 mM. a
b
Table 2. Product Selectivity Achieved in the Photochemistry of Naphthyl Dimethyl Phenyl Acetate (8) Incorporated in Bile Salt Micelles and Other Mediaa medium
9
10
11
12
hexaneb
35 92 80 83 86 81
17
4
21
10 13 12 17
2
1
NaDChb NaChb SDSb CTAC SDO
13
14
15
16
8 4 5 2 2 2
8 2
7 2 2
The numbers reported are average of at least five independent runs, error limit (5%. b Concentration of 8 in hexane, 1 mM. Concentrations of micelles: NaCh, 20 mM; NaDCh, 12 mM; SDS, 20 mM. a
hexane, implies suppression of rotational freedom of the encapsulated molecule in the microheterogeneous medium. In NaDCh aggregates, the exclusive formation of the ortho rearrangement product is suggestive of a nearly frozen radical pair. The formation of lesser amounts of 4 (85%) in NaCh than in NaDCh aggregates (99%) is consistent with the results of fluorescent probe, spin-label, and solubilization experiments which indicate a lesser rigidity of cholate micelles than deoxycholate micelles.13 Studies similar to those in bile salt micelles were extended to sodium dodecyl sulfate (SDS), cetyl trialkylammonium chloride (CTAC), and sodium dodecylcarboxylate (SDO) micelles for a comparative analysis of the bile salt with conventional micelles. Irradiation of 3 included in SDS resulted in the formation of 4 and 5 in 83% and 17% yields, respectively, with the absence of cage escape products implying the lack of cage escape of the radical pair A. On the other hand, a ratio of 1:0.2 for 4:5 in SDS micelles in comparison to 1:0.01 in NaDCh demonstrates that in SDS the guest binding site is not as rigid as the hydrophobic pockets of the NaDCh micelles. Similar results were obtained with CTAC (87% 4 and 12% 5) and SDO micelles (75% 4 and 21% 5) (Table 1). The product distributions obtained with all three long chain micelles are similar to that observed with NaCh micelles. Photochemistry of 1-Naphthyl Phenylacyl Ester Included within Sodium Cholate and Deoxycholate Micelles. 1-Naphthyl phenylacyl ester (8) upon irradiation undergoes a homolytic cleavage of the acyl-oxy bond from its excited singlet state to form 2-naphthyloxy and phenylacyl radical pair B (Scheme 2). In solution products 9-16 are obtained (Table 2).14 Irradiation of ester 8 included within the NaCh and NaDCh micelles showed a different product distribution from that in hexane. In the case of NaDCh micelles, higher product selectivity in favor of 9 (92%) was observed. NaCh micelles were also effective in inducing product selectivity upon irradiation of 8 (Table 2); nevertheless, selectivity is less than NaDCh. The (13) (a) Zhang, S.-Z.; Xie, J.-W.; Liu, C.-S. Anal. Chem. 2003, 75, 91. (b) Sugihara, G.; Yamakawa, K.; Murata, Y.; Tanaka, M. J. Phys. Chem. 1982, 86, 2784. (c) Fischer, L.; Oakenfull, D. Aust. J. Chem. 1979, 32, 31. (14) (a) Zhang, Z.; Turro, N. J.; Johnston, L.; Ramamurthy, V. Tetrahedron Lett. 1996, 37, 4861. (b) Turro, N. J.; Gould, I. R.; Baretz, H. B. J. Phys. Chem. 1983, 87, 531. (c) Lunazzi, L.; Ingold, K. U.; Scaiano, J. C. J. Phys. Chem. 1983, 87, 529.
formation of a small amount of 10 in cholate micelles may be due to the rotational motion permissible for radical pair B within these less rigid aggregates. Further, it was noticed that, unlike in hexane, recombination within the cholate aggregates had no competition from decarbonylation. Product distribution in cholate micelles clearly indicates that both NaCh and NaDCh aggregates do not dissociate within the lifetime of the singlet radical pair. The observed difference in the selectivity in product distribution between the cholate and deoxycholate micelles suggests a more rigid interior of the latter micelles. Distribution of photoproducts obtained from irradiation of 8 within NaCh micelles resembles those within conventional micelles of SDS, CTAC, and SDO (Table 2). Product distribution ratios for 9:10 of 1:0.16 in SDS, 1:0.14 in CTAC, and 1:0.21 in SDO indicate that though the generated radicals are forced to stay within the micellar phase there exists some amount of rotation in the long chain micelles, resulting in the formation of 10. Photochemistry of 4-Methyl Dibenzyl Ketone in Bile Salt Micelles. To evaluate the stability and rigidity of the bile salt aggregates on a longer time scale, photochemistry of guests 17 and 24, which react from their triplet excited states, was investigated. Excitation of 17 leads to its singlet excited state, which then undergoes efficient intersystem crossing to the corresponding triplet excited state that yields the homolytically R-cleaved triplet radical pairs D and F.15 These radical pairs can rearrange to yield the products 21, 22, and/or 23 or decarbonylate (>106 s-1) to the radical pair E to result in products 18-20. In a homogeneous medium such as hexane the triplet radical pair E rapidly diffuses apart and recombines to give a statistical mixture of 18, 19, and 20 of the ratio 1:2:1. Were the radicals completely confined, precluding cage escape, the only expected product of decarbonylation would be 19. Therefore, the ratio of 19 to 18 and 20 is a measure of the “cage effect” experienced by the decarbonylated radical pair. The following formula represents a numerical estimation of the cage effect (Fc):
Fc ) 19 - (18 + 20)/(18 + 19 + 20)
(ref 16)
Irradiation of 17 in hexane resulted in formation of 18, 19, and 20 with a cage effect of 0.05. Irradiation of the compound included (15) (a) Robbins, W. K.; Eastman, R. H. J. Am. Chem. Soc. 1970, 92, 6076. (b) Engel, P. S. J. Am. Chem. Soc. 1970, 92, 6074.
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Table 3. Product Selectivity Achieved in the Photochemistry of 1-Phenyl-3-p-tolyl-propan-2-one (17) Incorporated in Bile Salt Micelles and Other Mediaa medium
18
19
20
Fc
hexaneb NaDChb NaChb SDSb CTAC SDO
21 14 17 12 16 18
50 60 54 71 61 61
29 20 21 17 18 21
0.05 0.24 0.18 0.42 0.27 0.22
21 6 8 5
a The numbers reported are average of at least five independent runs, error limit (5%. b Concentration of 17 in hexane, 10-3 M. Concentrations of micelles: NaCh, 20 mM; NaDCh, 12 mM; SDS, 20 mM.
Table 4. Product Selectivity Achieved in the Photochemistry of Benzoin Ethyl Ether (24) Incorporated in Bile Salt Micelles and Other Mediaa type I medium
25d
26
waterb NaDChc NaChc SDS CTAC SDO
3 1
82 55 66 38 31 47
18 7 8
type II 28
30
31
type I:II product ratio
2 2
5 17 20
10 25 12 44 10 24
85:15 58:42 68:32 56:44 49:51 55:45
11
41 21
a The numbers reported are average of at least five independent runs, error limit (5%. b Saturated aqueous solution of 24 was prepared, filtered, and irradiated. c Concentrations: NaCh, 20 mM; NaDCh, 12 mM. d The reason for low yield of benzil (25) when compared with pinacol ether (26) is due to conversion of benzoyl radical to benzaldehyde and benzoic acid in aqueous solution.
in NaDCh micelle resulted in a cage effect of 0.24 (Table 3), in addition to a small amount of the rearrangement product 21 (6%). The cage effect with NaCh was expectedly smaller (0.18) than that with NaDCh. The relatively small Fc values with 17 as compared to the reactants 3 and 8 imply less efficient containment of the long-lived intermediates by NaCh and NaDCh aggregates. The observed trend is nevertheless consistent with the earlier two examples illustrating NaDCh micelles to be better at inducing selectivity. Irradiation of 17 included in SDS micelles yielded a cage effect (Fc) of 0.42, which could be translated as a higher confinement than obtained with bile salts.16 This observation is inconsistent with the earlier observed trend in the photochemistry of naphthyl benzoate (3) and naphthyl dimethyl phenyl acetate (8). This difference in behavior could be understood in terms of micellar size. SDS micelles being larger, comprising nearly 60 monomeric units, can confine the long-lived triplet radical pair even if a fraction of monomers dissociate from the aggregate. However, in the case of bile salt micelles, since the size is small (aggregation number varying between 6 and 10), the dissociation of each monomeric unit from the aggregate results in the loss of a greater fraction from the aggregate; thus there is less control of the radical pair, resulting in cage escape products due to the longer life of the radical pair. Also, one should note that the two reactions reveal different types of confinement provided by the medium. Photo-Fries reaction of naphthyl esters is an indication of rotational confinement, whereas photobehavior of dibenzyl ketone is a reflection of translational confinement. Photochemistry of Benzoin Ethyl Ether Included within Bile Salt Micelles. Benzoin ethyl ether (24) upon irradiation undergoes two reactions: R-cleavage to yield type I photoproducts and γ-hydrogen abstraction to yield type II products.17 Irradiation of benzoin ethyl ether (24) in water resulted in type I cage escape products in high yields (Table 4). In NaDCh micelles it gave considerable amounts of type II products (30, 31) (42%), a very (16) Turro, N. J.; Weed, G. C. J. Am. Chem. Soc. 1983, 105, 1861. (17) (a) Lewis, F. D.; Lauterbach, R. T.; Heine, H.-G.; Hartmann, W.; Rudolph, H. J. Am. Chem. Soc. 1975, 97, 1519. (b) Heine, H.-G. Tetrahedron Lett. 1972, 47, 4755.
small amount (2%) of in-cage recombination product (28), and a major amount of the cage escape product pinacol ether (26 in 55% yield). It is clear that the Norrish type II pathway is more favored within the interior of NaDCh micelles than in homogeneous media. Among the type I products, formation of a large amount of cage escape product (26) implies that the NaDCh aggregates probably remain in an equilibrium with its monomeric form. Another noticeable difference between the photochemistry in homogeneous medium and the NaDCh micellar medium is the formation of the rearranged product (28), though in a very small amount. This implies that radical pair H had been held within the cage for the duration of intersystem crossing and recombination. Although we assume that the reaction originates from T1, the reactive state of benzoin ethyl ether has not been clearly established. Based on the photobehavior of phenyl alkyl ketones, although one would conclude that the reactive state in the case of benzoin ethyl ether would be T1, during solution irradiation the R-cleavage products could not be quenched with triplet quenchers. Based on this, it is suggested that either the T1 must be cleaving at a rate faster than diffusion or the reaction occurs from S1. Since the intersystem crossing in phenyl alkyl ketones is over 1011 s-1, the cleavage from S1 must occur faster than this rate. Since generally R-cleavage is faster in T1 than in S1, Lewis and co-workers speculate that the products listed in Scheme 4 derive from the T1 state of benzoin ethyl ether. Similar product distributions, though to varying degrees, were observed when NaCh and SDS micelles were used to solubilize the compounds and irradiated (Table 4). The reason for selective formation of type II product arising from 24 included in SDS was speculated to be due to the orientational effect at the micellaraqueous phase interface.18 A similar feature may be responsible for the observed increase in 30 and 31 within bile salt micelles. A point to note is that the product 31 could also result from the β-cleavage process. The fact that cyclobutanol 30 is also formed in a significant amount along with 31 suggests that most likely both are formed via a Norrish type II pathway. (18) Devanathan, S.; Ramamurthy, V. J. Phys. Org. Chem. 1988, 1, 91.
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Experimental Section
Scheme 5
Conclusions The four photoreactions of the included photoactive compounds have helped establish bile salt micelles as capable of affecting selectivity in these reactions by restricting the freedom of the reactive intermediates. These natural solubilizers were effective in dictating the behavior of singlet radical pairs, but the effect on triplet radical pairs is clearly less pronounced. In all cases it is clear that sodium deoxycholate is more effective than sodium cholate in inducing selectivity. Failure of bile salts to induce selectivity in the cases of 1-phenyl-3-p-tolyl-propan2-one (17) and benzoin ethyl ether (24) suggests that these micelles are involved in a rapid equilibrium, because of which they are not able constrict the mobility of long-lived radical pairs. Comparing the selectivities achieved using bile salts with those from other long chain micelles discussed, bile salt micelles act as atypical surfactantssthe difference is primarily due to their smaller but strong and more rigid aggregates. A photochemical reaction could be visualized to proceed through the sequence shown in Scheme 5. A confined medium could influence a photoreaction at any or all stages of a photoreaction illustrated in Scheme 5. The medium may influence the reactant in the ground state, in the excited state, at the stage of reactive intermediates, and in the product. In the examples discussed here the influence mainly occurs at the stage of reactive intermediates. The four reactions discussed above generate either singlet or triplet radical pairs. The product distribution obtained within bile salt micelles from both types of radical pairs illustrate that these micelles are able to confine the short-lived singlet radical pair more efficiently than the long-lived triplet radical pair. The difference in the extent of confinement is due to the dynamic nature of the reaction vessel. To obtain better control on photoreactions one should utilize reaction vessels that are stable and leak proof on the time scale of the reactive intermediates going to products. In this context, dendrimers and closed capsules serve as better reaction vessels than a surfactant micelle having a dynamic structure.4
Materials. Sodium cholate (NaCh), sodium deoxycholate (NaDCh), and sodium dodecyl sulfate (SDS) were procured from Aldrich Co. and used without further purification. Photoreactive guests were prepared by procedures reported in our earlier work.4 Preparation of Complexes. Stock solutions of the compounds 3, 8, 17, and 24 were prepared in CH2Cl2-hexane (concentration around 3 mM). Volumes corresponding to 1.5-2 mg of the substrates were pipetted into a test tube. The solution was purged with air to remove the solvent, and a thin film of the substrate was obtained. Weighed amounts of the surfactants (100-200 mg) were added to this, followed by 5 mL of deionized water (in the case of SDS) or 5 mL of 0.2 M aqueous NaCl (in the case of bile salts). After the solutions were stirred for 3 h, they were filtered with the help of Whatman filter paper. The filtrates were taken in a test tube, purged with N2 for 15 min, and irradiated in a Pyrex test tube (40 min for 3 and 8, 10 min for 17, and 20 min for 24). The conversions were maintained around 30%. Extraction and Analysis of Photoproducts. After irradiation, solutions were diluted with deionized water to a surfactant concentration below their cmc’s (less than 21 mM for NaCh, 9 mM for NaDCh, 9 mM for SDS, and 1 mM for CTAC). The photoproducts were extracted by using ethyl acetate and diethyl ether mixture. In SDS, the extracting solvent was a 10% ether-hexane mixture, and the separatory funnel was shaken carefully to avoid the formation of emulsion. The extraction procedure was repeated three times. The organic layers were washed several times with water and dried over anhydrous MgSO4. The filtered solution was concentrated in vacuo and analyzed on an HP-5890 Series II gas chromatograph (GC) fitted with an SE-30 or HP-5 column. Product percentages were determined from the peak areas obtained by integration. Mass Balance Experiments. Mass balance experiments were carried out to confirm that product selectivities observed were not due to selective decomposition/loss of certain photoproducts. A standard solution with equal amounts of the photoreactive compound and an external standard (2 mg each in 5 mL of hexane-ethyl acetate) for GC (benzophenone or naphthalene) was prepared and injected in the GC. The ratio of the peak intensities was taken as a standard for 1:1 mixture by mass. To determine the mass balance after photochemistry, the irradiated samples were extracted and mixed with an equal mass (as that of the reactive guest taken) of internal standard and analyzed in the GC. The ratio of all peaks in the GC run with respect to the internal standard was considered to calculate the mass balance. In all cases the mass balance was estimated to be greater than 80%.
Acknowledgment. V.R. thanks the National Science Foundation for financial support of this research (CHE-0213042) and Professor N. J. Turro for useful discussions relating to supramolecular effects on photoreactions. LA0528192
