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

Abstract

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.

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.

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.

Experimental

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).