- Email: [email protected]
Helical aggregates from a chiral organogelator
TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 12 (2001) 477–480
Pergamon
Helical aggregates from a chiral organogelator† Uday Maitra,a,* Vijay Kumar Potluri,a N. M. Sangeetha,a P. Babua and A. R. Rajub a
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 064, India
b
Received 10 January 2001; accepted 13 February 2001
Abstract—A new class of pyrene based organogelators has been discovered, and a chiral gelator of this type has been shown to form helical aggregates upon gelation. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction In recent years a wide variety of small organic molecules have been demonstrated to act as gelling agents for organic solvents, and many potential applications have been envisaged for such gels.1,2 Although electron microscopic studies have revealed the existence of three-dimensional fibrous network structures in many of these organogels, models for the supramolecular aggregation of the gelator molecules (which ultimately lead to the formation of these fibers) are scarce.3 In this paper we present experimental evidence for the nature of the primary aggregates formed from a remarkably simple new chiral organogelator, which forms helical aggregates via a combination of hydrogen bonding, p-stacking and possibly dispersion interactions. We recently described the first donor–acceptor interaction mediated formation of organogels.4 In these systems, the donors were 1-pyrene-substituted bile acid derivatives, with trinitrofluorenone (TNF) acting as the electron acceptor. In order to explore and understand the gelation phenomenon at a molecular level, we synthesized alkyl appended pyrene derivatives in which the
linker was NH-CO-X (Fig. 1). We found that these derivatives, urethane 1, urea 2 and amide 3, formed gels in organic solvents (Table 1).5 Compounds 1–3 have a common NH-CO- linker between the pyrene unit and the alkyl group.
Table 1. Gel formation from 1–4 in various solvents. The compounds were typically tested for gelation at 2% w/wa
n-BuOH t-BuOH n-Octanol Cyclohexanol Cyclohexane n-Hexane n-Decane n-Dodecane CCl4 CHCl3 PhMe CH3CN a
1
2
3
4
G G G G G G G G P S S P
G G G G G G G G G S G P
G G G G G G G G G P G P
C C S S G G G G S S S C
G, gel; C, crystal; P, precipate; S, solution.
Figure 1. * Corresponding author. Fax: +91-80-360-1968; e-mail: [email protected] † Dedicated to Professor Ronald Breslow on the occasion of his 70th birthday. 0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S 0 9 5 7 - 4 1 6 6 ( 0 1 ) 0 0 0 7 3 - 8
U. Maitra et al. / Tetrahedron: Asymmetry 12 (2001) 477–480
478
Table 2. FT-IR CO stretching (cm−1) in the solid gel and solution in cyclohexane. The numbers in parentheses represent the concentration (mM). The NH signals showed a similar trend
1 2 3 4
Solid
Gel
Solution
1695 1629 1655 1689
1692, 1749a (36) 1630 (6) 1652 (5) 1688, 1745a (46)
1749 1668 1651 1746
(18) (6)b (17)b (17)
a
The relative intensities of the two peaks are 3:1 for 1 and 5:2 for 4, respectively. b Solution in CHCl3.
FT-IR studies in cyclohexane showed that the amide groups were as strongly hydrogen bonded in the gel state as they were in the solid state (Table 2). Variable temperature absorption spectral analysis in the same solvent (Fig. 2) showed pronounced hyperchromism upon gel melting, indicating de-stacking of the pyrene moieties upon this phase transition. It was therefore clear that these molecules were aggregating via both intermolecular hydrogen bonding (involving N-H and CO) and p-stacking interactions. Molecular modeling (INSIGHT II) showed that in order to maintain both intermolecular hydrogen bonding and stacking of the aromatic groups, the pyrene units must adopt a helical organization. This result indicated that there was a possibility of creating a non-racemic helical assembly by use of an appropriate chiral gelator. Further modeling with the (R)-(−)-2-octyl urethane derivative of pyrene (R)-4 showed a tightly packed, P-helical aggregate (Fig. 3).6 Compound (R)-4 not only formed gels in many solvents, these gels also had IR and variable
Figure 2. A plot of absorbance at 390 nm versus temperature for a 36 mM gel of 1 in cyclohexane (in a quartz cell of 1 mm path length). The molten gel at 60°C was cooled to 20°C and then heated to 60°C, while the absorbance was recorded at 5°C intervals.
Figure 3. INSIGHT II optimized assembly of 14 molecules of (R)-4 showing the P-helical organization.
temperature UV signatures (Table 2; entry 4) similar to their achiral counterparts.7 Finally, whereas the optical rotation of compound (R)-4 in cyclohexane (1.47%) at around 65°C (sol) was −6 deg cm2/g, upon cooling to room temperature (25°C) the optical rotation changed sign, and increased to +1680 deg cm2/g. Such a large optical rotation is consistent with the formation of a ‘hellicenoid’ organization,8 with the sign of the optical
Figure 4. CD spectra of the gels derived from (R)-4 and (S)-4 in cyclohexane at the indicated temperatures.
U. Maitra et al. / Tetrahedron: Asymmetry 12 (2001) 477–480
479
(m/z): 373. Anal. calcd for C25H27NO2: C, 80.40; H, 7.29; N, 3.75. Found: C, 80.58; H, 7.34; N, 3.53%.
Acknowledgements Support of this work by the Department of Science & Technology, New Delhi (grant no. SP/S1/G-08/96) is gratefully acknowledged. V.K. thanks the UGC and N.M.S. and P.B. thank the CSIR for financial support.
References
Figure 5. SEM of the dried gel (44 mM) of (S)-4 in cyclohexane.
rotation strongly supporting the formation of a P-helix. It was also found that the gel (but not the sol) showed CD, clearly indicating the formation of helical aggregates only in the gel state (Fig. 4).9 The (S)-enantiomer of 4, as expected, had optical rotation and CD data with opposite signs.10 Most of these new gels were also characterized by SEM analysis, which revealed a sub-micron sized fibrous network. The SEM of the xerogel derived from (R)-4 is shown in Fig. 5. We believe that our results show that it is possible to achieve the formation of chiral aggregates from simple chiral gelators in a predictable manner. The gelators described in this paper represent a new class of molecules in which both hydrogen bonding and pstacking have been demonstrated to play roles for their one-dimensional aggregation, with the alkyl chains possibly providing the right balance between solubility and crystallization. Further work to understand how these helical units assemble into fibers is in progress in our laboratories and the results from these studies will be reported in due course. 2. Experimental Data for (R)-4: Mp 125°C (from EtOH); [h]20 D =−35.4 (1.3, CHCl3); UV: umax (log m): [1% CHCl3/CH3CN] 383 (3.79), 340 (4.88), 277 (4.94), 242 (5.21); Fluorescence: uex 355 nm, uem 408 and 388 nm; FT-IR (cm−1, thin film): 1689 (s); 1H NMR (300 MHz, CDCl3): l 8.39 (br, 1H), 8.13–8.16 (m, 3H), 7.95–8.12 (m, 5H), 7.19 (br, 1H), 5.017 (m, 1H), 1.43–1.7 (m, 2H), 1.25–1.47 (m, 11H), 0.89 (t, J=6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): l 154.45, 131.36, 130.77, 128.29, 127.6, 127.25, 126.39, 126.03, 125.21, 125.06, 124.74, 119.95, 72.60, 36.21, 31.76, 29.12, 25.41, 22.58, 20.29, 14.07; LRMS
1. (a) See: Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133; (b) Terech, P.; Weiss, R. G. In Surface Characterisation Methods—Principles, Techniques and Applications; Milling, A. J., Ed. Low mass luminescent organogels. Marcel Dekker: New York, 1999; pp. 285–344 and references cited therein; (c) van Esch, J. H.; Feringa, B. L. Angew. Chem., Int. Ed. 2000, 39, 2263; (d) Abdallah, D. J.; Weiss, R. G. Adv. Mater. 2000, 12, 1237. 2. (a) Jung, J. H.; Ono, Y.; Shinkai, S. Tetrahedron Lett. 1999, 40, 8395–8399; (b) Inoue, K.; Ono, Y.; Kanekiyo, Y.; Ishi-i, T.; Yoshihara, K.; Shinkai, S. J. Org. Chem. 1999, 64, 2933–2937; (c) Hanabusa, K.; Maesaka, Y.; Kimura, M.; Shirai, H. Tetrahedron. Lett. 1999, 40, 2385– 2388; (d) van Esch, J.; Schoonbeek, F.; de Loos, M.; Kooijman, H.; Spek, A. L.; Kellogg, R. M.; Ferringa, B. L. Chem. Eur. J. 1999, 5, 937–950; (e) Ono, Y.; Nakashima, K.; Sano, M.; Kanekiyo, Y.; Inoue, K.; Hojo, J.; Shinkai, S. Chem. Commun. 1998, 1477; (f) Yoza, K.; Ono, Y.; Yoshihara, K.; Akao, T.; Shinmori, H.; Takeuchi, M.; Shinkai, S.; Reinhoudt, D. N. Chem. Commun. 1998, 907; (g) Vassilev, V. P.; Simanek, E. E.; Wood, M. R.; Wong, C.-H. Chem. Commun. 1998, 1865; (h) Ono, Y.; Nakashima, K.; Sono, M.; Hojo, J.; Shinkai, S. Chem. Lett. 1999, 1119; (i) Shi, C.; Huang, Z.; Kilic, S.; Xu, J.; Enick, R. M.; Beckman, E. J.; Carr, A. J.; Melendez, R. E.; Hamilton, A. D. Science 1999, 286, 1540; (j) Wang, R.; Geiger, C.; Chen, L.; Swanson, B.; Whitten, D. G. J. Am. Chem. Soc. 2000, 122, 2399; (k) Luo, X.; Li, C.; Liang, Y. Chem. Commun. 2000, 2091– 2092; (l) Jang, W.-D.; Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 2000, 122, 3232–3233. 3. Cuccia, L. C.; Lehn, J.-M.; Homo, J.-C.; Schmutz, M. Angew. Chem., Int. Ed. 2000, 39, 233–237. 4. Maitra, U.; Vijaykumar, P.; Chandra, N.; D’Souza, L. J.; Prasanna, M. D.; Raju, A. R. Chem. Commun. 1999, 595–596. 5. Analogues of 1 and 3 having a naphthalene unit in place of pyrene did not form gels. Pyrene derivatives with other linkers such as alkyl, ether, ester and ketone formed gels only in the presence of TNF. These results will be reported in a detailed publication. 6. Modeling of the other diastereomer showed that the side chains were loosely packed. 7. Homochiral 2-octyl pyrene-1-carboxylate did not form gel in any of the solvents reinforcing the necessity of a H-bonding linker for gelation in this class of molecules.
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U. Maitra et al. / Tetrahedron: Asymmetry 12 (2001) 477–480
8. (a) Nuckolls, N.; Katz, T. J.; Castellanos, L. J. Am. Chem. Soc. 1996, 118, 3767; (b) Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765; (c) Prince, R. B.; Brunsveld, L.; Meijer, E. W.; Moore, J. S. Angew. Chem., Int. Ed. 2000, 39, 228–230. 9. (a) For CD studies on a cholesterol based gel, see: Murata, K.; Aoki, M.; Suzuki, T.; Harada, T.; Kawa-
.
bata, H.; Komori, T.; Ohseto, F.; Ueda, K.; Shinkai, S. J. Am. Chem. Soc. 1994, 116, 6664; (b) For a report on helical microfibers, see: Hanabusa, K.; Yamada, M.; Kimura, M.; Shirai, H. Angew. Chem., Int. Ed. Engl. 1996, 35, 1949–1951. 10. Racemic 4 did not form a gel at comparable concentrations. For a similar result see Ref. 2c.
Pergamon
Helical aggregates from a chiral organogelator† Uday Maitra,a,* Vijay Kumar Potluri,a N. M. Sangeetha,a P. Babua and A. R. Rajub a
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 064, India
b
Received 10 January 2001; accepted 13 February 2001
Abstract—A new class of pyrene based organogelators has been discovered, and a chiral gelator of this type has been shown to form helical aggregates upon gelation. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction In recent years a wide variety of small organic molecules have been demonstrated to act as gelling agents for organic solvents, and many potential applications have been envisaged for such gels.1,2 Although electron microscopic studies have revealed the existence of three-dimensional fibrous network structures in many of these organogels, models for the supramolecular aggregation of the gelator molecules (which ultimately lead to the formation of these fibers) are scarce.3 In this paper we present experimental evidence for the nature of the primary aggregates formed from a remarkably simple new chiral organogelator, which forms helical aggregates via a combination of hydrogen bonding, p-stacking and possibly dispersion interactions. We recently described the first donor–acceptor interaction mediated formation of organogels.4 In these systems, the donors were 1-pyrene-substituted bile acid derivatives, with trinitrofluorenone (TNF) acting as the electron acceptor. In order to explore and understand the gelation phenomenon at a molecular level, we synthesized alkyl appended pyrene derivatives in which the
linker was NH-CO-X (Fig. 1). We found that these derivatives, urethane 1, urea 2 and amide 3, formed gels in organic solvents (Table 1).5 Compounds 1–3 have a common NH-CO- linker between the pyrene unit and the alkyl group.
Table 1. Gel formation from 1–4 in various solvents. The compounds were typically tested for gelation at 2% w/wa
n-BuOH t-BuOH n-Octanol Cyclohexanol Cyclohexane n-Hexane n-Decane n-Dodecane CCl4 CHCl3 PhMe CH3CN a
1
2
3
4
G G G G G G G G P S S P
G G G G G G G G G S G P
G G G G G G G G G P G P
C C S S G G G G S S S C
G, gel; C, crystal; P, precipate; S, solution.
Figure 1. * Corresponding author. Fax: +91-80-360-1968; e-mail: [email protected] † Dedicated to Professor Ronald Breslow on the occasion of his 70th birthday. 0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S 0 9 5 7 - 4 1 6 6 ( 0 1 ) 0 0 0 7 3 - 8
U. Maitra et al. / Tetrahedron: Asymmetry 12 (2001) 477–480
478
Table 2. FT-IR CO stretching (cm−1) in the solid gel and solution in cyclohexane. The numbers in parentheses represent the concentration (mM). The NH signals showed a similar trend
1 2 3 4
Solid
Gel
Solution
1695 1629 1655 1689
1692, 1749a (36) 1630 (6) 1652 (5) 1688, 1745a (46)
1749 1668 1651 1746
(18) (6)b (17)b (17)
a
The relative intensities of the two peaks are 3:1 for 1 and 5:2 for 4, respectively. b Solution in CHCl3.
FT-IR studies in cyclohexane showed that the amide groups were as strongly hydrogen bonded in the gel state as they were in the solid state (Table 2). Variable temperature absorption spectral analysis in the same solvent (Fig. 2) showed pronounced hyperchromism upon gel melting, indicating de-stacking of the pyrene moieties upon this phase transition. It was therefore clear that these molecules were aggregating via both intermolecular hydrogen bonding (involving N-H and CO) and p-stacking interactions. Molecular modeling (INSIGHT II) showed that in order to maintain both intermolecular hydrogen bonding and stacking of the aromatic groups, the pyrene units must adopt a helical organization. This result indicated that there was a possibility of creating a non-racemic helical assembly by use of an appropriate chiral gelator. Further modeling with the (R)-(−)-2-octyl urethane derivative of pyrene (R)-4 showed a tightly packed, P-helical aggregate (Fig. 3).6 Compound (R)-4 not only formed gels in many solvents, these gels also had IR and variable
Figure 2. A plot of absorbance at 390 nm versus temperature for a 36 mM gel of 1 in cyclohexane (in a quartz cell of 1 mm path length). The molten gel at 60°C was cooled to 20°C and then heated to 60°C, while the absorbance was recorded at 5°C intervals.
Figure 3. INSIGHT II optimized assembly of 14 molecules of (R)-4 showing the P-helical organization.
temperature UV signatures (Table 2; entry 4) similar to their achiral counterparts.7 Finally, whereas the optical rotation of compound (R)-4 in cyclohexane (1.47%) at around 65°C (sol) was −6 deg cm2/g, upon cooling to room temperature (25°C) the optical rotation changed sign, and increased to +1680 deg cm2/g. Such a large optical rotation is consistent with the formation of a ‘hellicenoid’ organization,8 with the sign of the optical
Figure 4. CD spectra of the gels derived from (R)-4 and (S)-4 in cyclohexane at the indicated temperatures.
U. Maitra et al. / Tetrahedron: Asymmetry 12 (2001) 477–480
479
(m/z): 373. Anal. calcd for C25H27NO2: C, 80.40; H, 7.29; N, 3.75. Found: C, 80.58; H, 7.34; N, 3.53%.
Acknowledgements Support of this work by the Department of Science & Technology, New Delhi (grant no. SP/S1/G-08/96) is gratefully acknowledged. V.K. thanks the UGC and N.M.S. and P.B. thank the CSIR for financial support.
References
Figure 5. SEM of the dried gel (44 mM) of (S)-4 in cyclohexane.
rotation strongly supporting the formation of a P-helix. It was also found that the gel (but not the sol) showed CD, clearly indicating the formation of helical aggregates only in the gel state (Fig. 4).9 The (S)-enantiomer of 4, as expected, had optical rotation and CD data with opposite signs.10 Most of these new gels were also characterized by SEM analysis, which revealed a sub-micron sized fibrous network. The SEM of the xerogel derived from (R)-4 is shown in Fig. 5. We believe that our results show that it is possible to achieve the formation of chiral aggregates from simple chiral gelators in a predictable manner. The gelators described in this paper represent a new class of molecules in which both hydrogen bonding and pstacking have been demonstrated to play roles for their one-dimensional aggregation, with the alkyl chains possibly providing the right balance between solubility and crystallization. Further work to understand how these helical units assemble into fibers is in progress in our laboratories and the results from these studies will be reported in due course. 2. Experimental Data for (R)-4: Mp 125°C (from EtOH); [h]20 D =−35.4 (1.3, CHCl3); UV: umax (log m): [1% CHCl3/CH3CN] 383 (3.79), 340 (4.88), 277 (4.94), 242 (5.21); Fluorescence: uex 355 nm, uem 408 and 388 nm; FT-IR (cm−1, thin film): 1689 (s); 1H NMR (300 MHz, CDCl3): l 8.39 (br, 1H), 8.13–8.16 (m, 3H), 7.95–8.12 (m, 5H), 7.19 (br, 1H), 5.017 (m, 1H), 1.43–1.7 (m, 2H), 1.25–1.47 (m, 11H), 0.89 (t, J=6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): l 154.45, 131.36, 130.77, 128.29, 127.6, 127.25, 126.39, 126.03, 125.21, 125.06, 124.74, 119.95, 72.60, 36.21, 31.76, 29.12, 25.41, 22.58, 20.29, 14.07; LRMS
1. (a) See: Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133; (b) Terech, P.; Weiss, R. G. In Surface Characterisation Methods—Principles, Techniques and Applications; Milling, A. J., Ed. Low mass luminescent organogels. Marcel Dekker: New York, 1999; pp. 285–344 and references cited therein; (c) van Esch, J. H.; Feringa, B. L. Angew. Chem., Int. Ed. 2000, 39, 2263; (d) Abdallah, D. J.; Weiss, R. G. Adv. Mater. 2000, 12, 1237. 2. (a) Jung, J. H.; Ono, Y.; Shinkai, S. Tetrahedron Lett. 1999, 40, 8395–8399; (b) Inoue, K.; Ono, Y.; Kanekiyo, Y.; Ishi-i, T.; Yoshihara, K.; Shinkai, S. J. Org. Chem. 1999, 64, 2933–2937; (c) Hanabusa, K.; Maesaka, Y.; Kimura, M.; Shirai, H. Tetrahedron. Lett. 1999, 40, 2385– 2388; (d) van Esch, J.; Schoonbeek, F.; de Loos, M.; Kooijman, H.; Spek, A. L.; Kellogg, R. M.; Ferringa, B. L. Chem. Eur. J. 1999, 5, 937–950; (e) Ono, Y.; Nakashima, K.; Sano, M.; Kanekiyo, Y.; Inoue, K.; Hojo, J.; Shinkai, S. Chem. Commun. 1998, 1477; (f) Yoza, K.; Ono, Y.; Yoshihara, K.; Akao, T.; Shinmori, H.; Takeuchi, M.; Shinkai, S.; Reinhoudt, D. N. Chem. Commun. 1998, 907; (g) Vassilev, V. P.; Simanek, E. E.; Wood, M. R.; Wong, C.-H. Chem. Commun. 1998, 1865; (h) Ono, Y.; Nakashima, K.; Sono, M.; Hojo, J.; Shinkai, S. Chem. Lett. 1999, 1119; (i) Shi, C.; Huang, Z.; Kilic, S.; Xu, J.; Enick, R. M.; Beckman, E. J.; Carr, A. J.; Melendez, R. E.; Hamilton, A. D. Science 1999, 286, 1540; (j) Wang, R.; Geiger, C.; Chen, L.; Swanson, B.; Whitten, D. G. J. Am. Chem. Soc. 2000, 122, 2399; (k) Luo, X.; Li, C.; Liang, Y. Chem. Commun. 2000, 2091– 2092; (l) Jang, W.-D.; Jiang, D.-L.; Aida, T. J. Am. Chem. Soc. 2000, 122, 3232–3233. 3. Cuccia, L. C.; Lehn, J.-M.; Homo, J.-C.; Schmutz, M. Angew. Chem., Int. Ed. 2000, 39, 233–237. 4. Maitra, U.; Vijaykumar, P.; Chandra, N.; D’Souza, L. J.; Prasanna, M. D.; Raju, A. R. Chem. Commun. 1999, 595–596. 5. Analogues of 1 and 3 having a naphthalene unit in place of pyrene did not form gels. Pyrene derivatives with other linkers such as alkyl, ether, ester and ketone formed gels only in the presence of TNF. These results will be reported in a detailed publication. 6. Modeling of the other diastereomer showed that the side chains were loosely packed. 7. Homochiral 2-octyl pyrene-1-carboxylate did not form gel in any of the solvents reinforcing the necessity of a H-bonding linker for gelation in this class of molecules.
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U. Maitra et al. / Tetrahedron: Asymmetry 12 (2001) 477–480
8. (a) Nuckolls, N.; Katz, T. J.; Castellanos, L. J. Am. Chem. Soc. 1996, 118, 3767; (b) Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765; (c) Prince, R. B.; Brunsveld, L.; Meijer, E. W.; Moore, J. S. Angew. Chem., Int. Ed. 2000, 39, 228–230. 9. (a) For CD studies on a cholesterol based gel, see: Murata, K.; Aoki, M.; Suzuki, T.; Harada, T.; Kawa-
.
bata, H.; Komori, T.; Ohseto, F.; Ueda, K.; Shinkai, S. J. Am. Chem. Soc. 1994, 116, 6664; (b) For a report on helical microfibers, see: Hanabusa, K.; Yamada, M.; Kimura, M.; Shirai, H. Angew. Chem., Int. Ed. Engl. 1996, 35, 1949–1951. 10. Racemic 4 did not form a gel at comparable concentrations. For a similar result see Ref. 2c.