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Synlett 2007(4): 0628-0632  
DOI: 10.1055/s-2007-967977
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Spectral Properties of a Deoxyribose-Phthalocyanine ­Conjugate Using a Sonogashira Coupling Reaction

Mamidi Ramesh Reddy, Norio Shibata*, Hideyuki Yoshiyama, Shuichi Nakamura, Takeshi Toru*
Department of Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa, Nagoya 466-8555, Japan
Fax: +81(52)7355442; e-Mail: nozshiba@nitech.ac.jp; e-Mail: toru@nitech.ac.jp;
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Publication History

Received 16 December 2006
Publication Date:
21 February 2007 (online)

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Abstract

The synthesis of a deoxyribose-phthalocyanine con­jugate using a Sonogashira coupling reaction of zinc(II) tetraiodo­phthalocyaninate with alkynyl-ribose is described. The peripheral deoxyribose substituents improve water solubility as well as the ­lipophilicity/hydrophobicity balance without decreasing photosensitivity. The log P value, a strong absorption band at long wavelengths and strong fluorescence emission means that this compound should be effective for photodynamic therapy.

Key words

phthalocyanines - photodynamic therapy - palladium coupling - nucleosides - porphyrins

18

Zinc(II) tetrakis({2-Deoxy-3,5-bis[O-(p-toluoyl)]-α,β-d-ribofuranosyl}ethynyl) phthalocyaninate (4): A mixture of 2 [17] (250.0 mg, 0.231 mmol), 3 [16] (524.8 mg, 1.39 mmol), Pd(PPh3)2Cl2 (20 mg) and CuI (10 mg) were dried under vacuum for 1 h. To this mixture, anhyd DMF (2.5 mL) was added followed by Et3N (1 mL) and allowed to stir at r.t. for 72 h. The solvent was removed by evaporation and the crude green solid was purified by silica gel chromatography (EtOAc-hexane, 40:60) to furnish 4 as a blue solid (360.0 mg, 75%); IR (KBr): 2954, 2229, 1720, 1611, 1488, 1386, 1271, 1178, 1100, 1020, 837, 752 cm-1; 1H NMR (600MHz, acetone-d 6 ): δ = 8.64 (br s, 8 H, Ar-H), 8.23-8.06 (m, 20 H, Ar-H), 7.42-7.37 (m, 16 H, Ar-H), 5.87-5.56 (m, 8 H, 1′,3′-H), 4.95-4.71 (m, 12 H, 4′,5′-H), 3.11-2.98 (m, 8 H, 2′-H), 2.46-2.20 (m, 24 H, Ar-CH3); MALDI-TOF MS (Matrix: dithranol): m/z calcd for: 2080.61, 2081.61, 2082.61, 2083.60, 2084.61, 2085.60; found: 2080.55, 2081.54, 2083.54, 2084.54, 2085.54; UV/Vis (dioxane): λmax (log ε) = 686 (5.5), 655 (4.6), 617 (4.7), 360 nm (5.0); UV/Vis (toluene): λmax (log ε) = 691 (5.4), 660 (4.7), 622 (4.7), 360 nm (4.9); fluorescence (DMSO): λem = 701, 764 nm [excitation at 650 nm; φf = 0.25; zinc(II) tetra-tert-butylphthalocyaninate was used as reference (φf = 0.3 in DMSO) [4] ].

19

Zinc(II) tetrakis[(2-deoxy-α,β-d-ribofunosyl)ethynyl] phthalocyaninate (1): A mixture of 4 (20.1 mg, 0.0096 mmol), and K2CO3 (14.4 mg, 0.104 mmol), in MeOH-THF (2:1, 3 mL) was stirred at r.t. for 48 h. The reaction mixture was filtered and washed with MeOH. The MeOH was evaporated off to furnish a dark blue solid, to which was added H2O (4.0 mL, pH adjusted to 6) and filtered. The solid was washed with H2O and 30% of acetone in H2O and purified twice by Sephadex® G-25 using MeOH as an eluent. Evaporation of the solvent gave a crude blue solid. Further purification by recrystallization with MeOH and EtOAc gave pure 1 (8.2 mg, 80%); IR (KBr): 2954, 2229, 1720, 1611, 1488, 1386, 1271, 1178, 1100, 1020, 837, 752 cm-1; 1H NMR (600MHz, CD3OD): δ = 8.54 (br s, 8 H, Ar-H), 7.91 (br s, 4 H, Ar-H), 5.31 (br s, 4 H, 1′-H), 4.52 (br s, 2 H, 4′-H), 4.43 (br s, 2 H, 4′-H), 4.21 (br s, 2 H, 3′-H), 4.02 (br s, 2 H, 3′-H), 3.83-3.77 (m, 8 H, 5′-H), 2.87 (br s, 2 H, 2′-H), 2.53-2.41 (br s, 6 H, 2′-H); MALDI-TOF MS (Matrix: α-CHCA): m/z calcd for: 1136.27, 1137.27, 1138.27, 1139.27, 1140.26, 1141.27, 1142.27, 1143.27; found: 1136.27, 1137.28, 1138.29, 1139.30, 1142.23, 1143.29; UV/Vis (DMSO): λmax (log ε) = 691 (5.4), 658 (4.5), 621 (4.6), 366 nm (4.9); UV/Vis (DMSO-H2O, 1:1): λmax (log ε) = 693 (4.6), 642 (4.7), 360 nm (4.9); (DMSO-H2O, 1:19): λmax (log ε) = 689 (4.7), 638 (4.68) 348 nm (4.8); fluorescence (DMSO): λem = 701, 765 nm (φf = 0.22); (DMSO-H2O, 1:19): λem = 685, 701 nm (0.5 × 10-5 M).