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1,1’,1’’,1’’’-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium Tetrabromide

Yoshinobu Ishikawa
Takeshi Yamashita
Satoshi Fujii
1 and
Tadayuki Uno
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
Author to whom correspondence should be addressed.
Molbank 2010, 2010(4), M704;
Submission received: 8 October 2010 / Accepted: 28 October 2010 / Published: 1 November 2010


Cationic porphyrins interact strongly with guanine quadruplex DNA (G-quadruplex). We herein report the preparation of a cationic porphyrin bearing quinolinium side arms, 1,1’,1’’,1’’’-[porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium tetrabromide (mQu), as a potential G-quadruplex ligand.

Graphical Abstract

Guanine quadruplex DNA (G-quadruplex) of a single-stranded overhang at the end of chromosomes is an attractive drug target for cancer treatment, because macrocyclic compounds like cationic tetra-(N-methyl-4-pyridyl)porphyrin (TMPyP4) stabilize G-quadruplex structures, and thus show anti-telomerase and anti-cancer activity [1,2,3,4]. We previously synthesized G-quadruplex-interacting porphyrins with cationic side arms at para- or meta-position of all phenyl groups of tetratolyl porphyrin [5]. These porphyrins were found to stabilize an anti-parallel G-quadruplex more greatly than TMPyP4. Among those cationic porphyrins, 1,1’,1’’,1’’’-[porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetrapyridinium tetrabromide (mPy) exhibited the highest ability to stabilize the G-quadruplex. Cationic porphyrins with more hydrophobic side arms could stabilize the G-quadruplex more greatly, because hydrophobic interaction is entropically favorable in water, which determines the Gibbs energy of binding (i.e., binding affinity). Thus, we herein report the preparation of a cationic porphyrin bearing quinolinium side arms, 1,1’,1’’,1’’’-[porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium tetrabromide (mQu), as a potential G-quadruplex ligand.
Scheme 1. Preparation of mQu.
Scheme 1. Preparation of mQu.
Molbank 2010 m704 sch001
The title compound was prepared successfully by the reaction of mBr with an excess of quinoline. The 1H-NMR, ESI-MS and elemental analyses gave satisfactory results.


1H-NMR spectra were recorded on a JEOL GX-400 spectrometer. Electrospray-ionization time-of-flight (ESI-TOF) mass spectrum was recorded on a Micromass LCT Premier™. Elemental analysis was performed at the Analytical Center, Kumamoto University. The starting material mBr was synthesized according to a previously published method [6].

1,1’,1’’,1’’’-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium tetrabromide (mQu)

A solution of mBr (42 mg, 0.043 mmol) in quinoline (5 mL) was refluxed for 1 h with stirring. After cooling to room temperature, the purple solids were collected and dried in vacuo (yield: 87%). 1H-NMR (DMSO-d6): 6.78 (s, 8H, -CH2-), 7.87–8.03 (m, 8H, phenyl H-5 and H-6), 8.18 (t, J = 6.2 Hz, 4H, quinoline H-6), 8.21 (d, J = 6.4 Hz, 4H, phenyl H-4), 8.29 (m, 8H, pyridyl H-3 and H-5), 8.33 (s, 4H, phenyl H-2), 8.33 (m, 4H, quinoline H-3), 8.44 (t, J = 6.2 Hz, 4H, quinoline H-7), 8.65 (d, J = 7.0 Hz, 4H, quinoline H-5), 8.70 (s, 4H, β-pyrrolic H), 8.76 (s, 4H, β-pyrrolic H), 8.87 (d, J = 6.2 Hz, 4H, quinoline H-8), 9.52 (m, 4H, quinoline H-4) , 10.05 (m, 4H, quinoline H-2). ESI-TOF MS (m/z): Calcd for C84H62N8, 295.63 [M]+4. Found: 295.61. Elemental analysis: Calcd. for C84H62N8Br4 4 H2O C7H7N: C, 65.54; H, 4.55; N, 7.40. Found: C, 65.58; H, 4.44; N, 7.23. UV-vis [λ, nm (ε, cm–1M–1); DMSO]: 422 (1.72 × 105), 515 (2.36 × 104), 550 (1.17 × 104), 590 (1.72 × 103), 646 (6.46 × 103).

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3


This work was supported by grants (Nos. 12771437 and 14771311 to Y.I.) for Science Research from Japan Society for Promotion of Science.

References and Notes

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  5. Yamashita, T.; Uno, T.; Ishikawa, Y. Stabilization of guanine quadruplex DNA by the binding of porphyrins with cationic side arms. Bioorg. Med. Chem. 2005, 13, 2423–2430. [Google Scholar] [CrossRef] [PubMed]
  6. Bookser, B.C.; Bruice, T.C. Syntheses of quadruply two- and three-atom, aza-bridged, cofacial bis(5,10,15,20-tetraphenylporphyrins). J. Am. Chem. Soc. 1991, 113, 4208–4218. [Google Scholar] [CrossRef]

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MDPI and ACS Style

Ishikawa, Y.; Yamashita, T.; Fujii, S.; Uno, T. 1,1’,1’’,1’’’-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium Tetrabromide. Molbank 2010, 2010, M704.

AMA Style

Ishikawa Y, Yamashita T, Fujii S, Uno T. 1,1’,1’’,1’’’-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium Tetrabromide. Molbank. 2010; 2010(4):M704.

Chicago/Turabian Style

Ishikawa, Yoshinobu, Takeshi Yamashita, Satoshi Fujii, and Tadayuki Uno. 2010. "1,1’,1’’,1’’’-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium Tetrabromide" Molbank 2010, no. 4: M704.

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