Synthesis and CD spectrum of chiral porphyrin dimer

Tetrahedron Letters, Vol. 36, No. 33, pp. 5905-5908, 1995 Elsevier Science Ltd Printed in Great Britain 0040-4039/95 $9.50+0.00

Pergamon 0040-4039(95)01138-2

Synthesis and CD Spectrum of Chiral Porphyrin Dimer Tadashi Ema,* Shuichi Nemugaki, Sadao Tsuboi, and Masanori Utaka* Department of Applied Chemistry, Okayama University, Tsushima, Okayama 700, Japan

Abstract: Chiral porphyrin dimer 1 was synthesized. The UV-vis spectrum of 1 was almost

identical with that of the corresponding monomer 2. The circular dichroism induced in the Soret region of 1 was very strong and of the split type due to the chiral exciton coupling.

Porphyrin derivatives including chlorophylls and bacteriochlorophylls are spatially arranged in the naturally-occurring proteins such as the photosynthetic reaction center complex 1 and cytochrome c oxidase. Recent model studies of the photosynthetic reaction centers and the metalloenzymes using synthetic porphyrin dimers have demonstrated that the distance and orientation between two porphyrins are significant factors in the electron (or energy) transfer efficiencies2 and in the catalytic activities.3 Porphyrin derivatives have also been artificially disposed along DNA helices and polypeptides. 4

Accordingly, the development of the

spectroscopic technique to detect the mode of spatial arrangement of porphyrin chromophores is an important subject. Circular dichroism (CD) spectroscopy is very sensitive both to distance and to orientation between chromophores. 5 The origin of the CD induced in the porphyrin absorption region has been the focus of interest. 6 Here we report the design, synthesis, and CD spectrum of a novel chiral porphyrin dimer (1S,2S)I with C2 symmetry. 7 We adopted the synthetic strategy for the chiral porphyrin dimer as shown in Scheme 1, which allows us to examine various chiral spacers to control the distance and angle between the porphyrins. The aliphatic spacer was selected because of its little influence on the CD spectrum. The dipyrromethane 3 was prepared by coupling of two equivalents of benzyl 3,4-dimethylpyrrole-l-carboxylate with methyl 4-formylbenzoate in the presence ofp-toluenesulfonic acid in refluxing benzene followed by hydrogenolysis over Pd/C in MeOH, and was condensed with 48 in aq HCIO4/MeOH to give the porphyrin 2 in 23% yield. 9 Hydrolysis of 2 with aq NaOH/THF followed by treatment with (COC1)2 in CH2C12 afforded the corresponding acid chloride, which was coupled with (1S,2S)-l,2-diaminocyclohexane to give the target chiral porphyrin dimer (1S,2S)lin 15% yield (from 2).

5905

5906

Scheme 1

Et M e - ~ cO2H OHC-.T~ Et M e O 2 C - ~ ' ~ NH ~ Me

R= ~

E

t

Me~~..~Et

Me ~t-..~H OHC.~.~Et "i~ "CO2H Me Et 3

Et

Me

Me

Et

4

R-CO2Me 2

c,,

J=

R H H R (1S,2S)-I

Reagents: (a) aq HC104/MeOH. (b) aq NaOHfFHF. (c) (COCI)JCH2C12. (d) (1S,2S)-diaminocyclohexane/pyridine. The 1H NMR spectrum of (1S,2S)-1 indicated that the porphyrin moieties rotate rapidly on an NMR time scale around the amide bond axes (around the bond between the amide-N and the cyclohexyl-C ( ~ , ~2 in Fig. 2) as well as around the bond between the amide-C and the phenyl-C). 10 The signals of the porphyrin peripheral protons such as the meso-protons and the B-methyl substituents were shifted as shown in Fig. 2 due to the ring current effect of the vicinal porphyrin moiety. Computer-assisted molecular modeling of (1S,2S)-1 indicated that the free rotation of the porphyrin moieties around the amide bond axes allows the methyl groups at the 13-positions, which are distal to the phenyl group at the meso-position, to be placed at the shielding region above the adjacent porphyrin plane (ca. 8/k), in accord with the observed largest upfield shift (Fig. 2). The UV-vis absorption spectrum of (1S,2S)-1 was almost identical with that of the monomer 2, which might lead us to conclude that no electronic interaction operates between the two porphyrin chromophores. However, the CD spectrum of (1S,2S)-1 showed the split Cotton effects of the opposite signs in the Soret region as shown in Fig. 1. This CD can be attributed to the chiral exciton coupling between the two porphyrin chromophores, because the CD intensity is very strong ([0] = +29 X 104 (412 nm), [0] = -8.5 X 104 (392 nm)), and because the sign pattern can be explained by the exciton chimlity method; the compound 1 having the positive chirality shows the positive and the negative Cotton effect at longer and shorter wavelength region, respectively.5 The apparent CD intensity of 1 is one of the largest, compared with those of the naturally-occurring hemoproteins, 6a although the average center-to-center distance between two porphyrin moieties is relatively long (16 A).

Thus, the CD induced by the exciton coupling between

porphyrin chromophores can be larger than that caused by the nearby amino acid residues in hemoproteins. It is well-known that the Soret band consists of doubly degenerate electric transition moments which are perpendicular to each other. 11 So in this particular case, it is reasonable to assume that the split Cotton effects

5907

observed in the Soret region were induced by the chiral exciton couplings between the electric transition moments (/~xl or/~y I in Fig. 2) in one porphyrin plane and those (/~xz or/~y2) in the other. Our preliminary theoretical calculations supported r

r

it +30

and

also

complicated

revealed

feature

observed CD, +20

the the

which mainly

comes from the direction of the electric

×

of

+10

transition

moments

which are tilted by 45* from the direction (Fig. 2). 12

meso-meso

Systematic studies are now going on. -10

300

400

L 500

600

Wavelength (nm)

Fig. l. Circular dichroism spectrum of (1S,2S)-1 in CHCI3 at 20 *C.

Fig. 2. The electric transition moments (/~, ~) of the Soret ~

H¢2

band (bold arrows). The numerical values in the parentheses indicate the differences in the 1H NMR chemical shift (ppm)

~O m

~

(-0

O

between (1S,2S)-1 and 2. Negative sign indicates the upfield-

(-°'4~.~/02)

shift of the chemical shifts of (1S,2S)-1 compared with those

~-o.1a ~ ~ _ ~

)../)

of 2. The dihedral angles (¢1, ~ ) are defined by the following four atoms; amide-C, amide-N, cyclohexyl-C, cyclohexyl-H.

Acknowledgements:

We thank Professor M. Sisido and Professor N. Baba at Okayama University for

the measurement of CD spectra. We thank Dr. S. Kajiyama and Mr. M. Kuragaki for the measurement of FAB mass spectra and UV-vis spectra, respectively. We thank Dr. T. Mizutani at Kyoto University for valuable discussions about the mechanisms of CD. We are grateful to SC-NMR Laboratory of Okayama University for the measurement of NMR spectra.

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R E F E R E N C E S A N D NOTES:

1. (a) Deisenhofer, J.; Michel, H. Angew. Chem., Int. Ed. EngL 1989, 28, 829. (b) Huber, R. Angew. Chem., Int. Ed. Engl. 1989, 28, 848. 2. (a) Osuka, A.; Maruyama, K.; Mataga, N.; Asahi, T.; Yamazaki, I.; Tamai, N. J. Am. Chem. Soc. 1990, 112, 4958. (b) Sessler, J. L.; Johnson, M. R.; Creager, S. E.; Fettinger, J. C.; Ibers, J. A.J. Am. Chem. Soc. 1990, 112, 9310. (c) Gust, D.; Moore, T. A.; Moore, A. L.; Gao, F; Luttrull, D.; DeGraziano, J. M.; Ma, X. C.; Makings, L. R.; Lee, S.-J.; Trier, T. T.; Bittersmann, E.; Seely, G. R.; Woodward, S.; Bensasson, R. V.; Roug6e, M.; De Schryver, F. C.; Van der Auweraer, M. J. Am. Chem. Soc. 1991, 113, 3638. (d) Helms, A.; Heiler, D.; McLendon, G. J. Am. Chem. Soc. 1992, 114, 6227. 3. (a) Collman, J. P.; Hutchison, J. E.; Lopez, M. A.; Tabard, A.; Guilard, R.; Seok, W. K.; Ibers, J. A.; L'Her, M. J. Am. Chem. Soc. 1992, 114, 9869. (b) Naruta, Y.; Sasayama, M.; Sasaki, T. Angew. Chem., Int. Ed. EngL 1994, 33, 1839.

4. Pasternack, R. F.; Giannetto, A.; Pagano, P.; Gibbs, E. J..L Am. Chem. Soc. 1991, 113, 7799. 5. Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopy-Exciton Coupling in Organic Stereochemistry; University Science Books: Mill Valley, CA, 1983. 6. (a) Myer Y. P.; Pande, A. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1978; Vol. 3, pp.271-322. (b) Hsu, M.-C.; Woody, R. W. J. Am. Chem. Soc. 1971, 93, 3515. (c) Mizutani, T.; Ema, T.; Yoshida, T.; Kuroda, Y.; Ogoshi, H. lnorg. Chem. 1993, 32, 2072. (d) Mizutani, T.; Ema, T.; Yoshida, T.; Renn6, T.; Ogoshi, H. lnorg. Chem. 1994, 33, 3558. 7. To the best of our knowledge this is the first report on the CD of the covalently linked porphyrin dimer. For aggregated porphyrins' CD, see: (a) Urry, D. W.; Pettegrew, J. W. J. Am. Chem. Soc. 1967, 89, 5276. (b) Fuhrhop, J. H.; Demoulin, C.; Boettcher, C.; K6ning, J.; Siggel, U. J. Am. Chem. Soc. 1992, 114, 4159. (c) lmada, T.; Murakami, H.; Shinkai S. J. Chem. Soc., Chem. Comm. 1994, 1557. 8. Paine III, J. B.; Woodward, R. B.; Dolphin, D. J. Org. Chem. 1976, 41, 2826. 9. Arsenault, G. P.; Bullock, E.; MacDonald, S. F. J. Am. Chem. Soc. 1960, 82, 4384. 10. 1 : 1H NMR(CDCI3, 500 MHz) -3.28 (br s, 2H, NH), -3.12 (br s, 2H, NH), 1.70 (m, 2H, cyclohexylCH2), 1.81 (m, 2H, cyclohexyl-CH2), 1.85 (t, 12H, J = 7.5 Hz, CH2CH3), 1.93 (t, 12H, J = 7.5 Hz, CH2CH3), 2.02 (m, 2H, cyclohexyl-CH2), 2.43 (s, 12H, CH3), 2.57 (m, 2H, cyclohexyl-CH2), 3.22 (s, 12H, CH3), 4.05 (q, 8H, J = 7.5 Hz, CH2CH3), 4.09 (q, 8H, J = 7.5 Hz, CH2CH3), 4.46 (m, 2H, cyclohexyl-CH), 7.51 (d, 2H, J = 7 Hz, NH), 8.21 (ABq, 4H, J = 8 Hz, phenyl-H), 8.32 (ABq, 4H, J = 8 Hz, phenyl-H), 10.01 (s, 4H, meso-H), 10.04 (s, 2H, meso-H); UV-vis (CHCI3) ~.max (loge) 405 (5.39), 504 (4.32), 538 (4.00), 571 (3.95), 624 (3.48), 655 (3.36); HR FAB-MS (3-nitrobenzylalcohol matrix) m/z calcd for C84H9502N10 1275.7639, found 1275.7582. 11. (a) Gouterman, M. J. Mol. Spectroscopy 1961, 6, 138. (b) Gouterman, M.; Wagni~.re, G. H.; Snyder, L. C.J. Mol. Spectroscopy 1963, 11, 108. 12. The dihedral angles (~, q02) were rotated by 30 ° increments and the rotational strengths were calculated in a manner similar to that reported previously. 6d

(Received in Japan 27 April 1995; accepted 19 June 1995)