Elsevier

Synthetic Metals

Volume 260, February 2020, 116256
Synthetic Metals

Synthesis and characterization of new partially-aggregated water-soluble polyether-triazole linked zinc(II) phthalocyanines as photosensitizers for PDT studies

https://doi.org/10.1016/j.synthmet.2019.116256Get rights and content

Highlights

  • Novel dinitriles were synthesized and confirmed using spectral and analytical techniques.

  • New significant compounds and remarkable synthetic routes have been achieved.

  • The synthesis and characterization of highly water-soluble phthalocyanines with terminal carboxylic acid functionalities.

  • This phthalocyanines present photophysical features, indicating that they could be used for photodynamic therapy.

  • This report also indicates singlet oxygen quantum yields of zinc(II) phthlocyanines.

Abstract

Peripheral and non-peripheral octa-carboxylated water-soluble zinc(II) phthalocyanines with clicked polyethylene glycol linkers have been prepared. Different multistep reaction pathways have been attempted and compared for the preparation of the phthalonitrile precursors. Novel compounds have been characterized by combination of elemental analysis, 1H and 13C NMR, FT-IR, U–vis and MS spectral data. Both phthalocyanines were proved to be water soluble. Their singlet oxygen generation was determined in both water and DMSO to assess their potential of photosensitizers for photodynamic therapy.

Introduction

Phthalocyanines and related compounds are one of the largest groups of tetrapyrrolic macrocycles and widely investigated in many areas such as electrochromic and photochromic substances, photosensitizers for dye-sensitized solar cells, liquid crystals, Langmuir-Blodgett films, chemical sensors, industrial catalytic systems and material chemistry, semiconductor devices, molecular metals, and photocopying devices [1,2]. In the past few decades, in addition to their traditional uses mentioned above, phthalocyanines strated to appear as ideal second generation photosensitizers for photodynamic therapy (PDT) [3], in particular due to their high singlet oxygen yield and other optical properties [4]. Nonetheless, the low solubility of unsubstituted phthalocyanines in aqueous media and common organic solvents is a strong drawback [5].

An intrinsic advantage of phthalocyanine as PDT photosensitizers is their intense absorption at near-infrared wavelengths (ca. 700 nm), ideal for various types of cancers as it allows to irradiate in the phototherapeutic window. Especially, water soluble phthalocyanines are most promising photosensitizers [6]. Ideally, PDT photosensitizers should exhibit high solubility in water, strong absorption in the 600−800 nm region (deep red) and high singlet oxygen quantum yields.

Attachment of carboxylic acid groups attached through triazole moieties to Pcs is expected to significantly increase the solubility of Pcs in water and limit their aggregation. Generally, high solubility and high tendency of aggregation properties of phthalocyanines in water limit their singlet oxygen generation yields and thus significantly restrict their photodynamic therapy potential [7]. Carboxylic acids with triazole groups attached to metallo-phthalocyanines through polyethylene glycol linkers could confer solubility in aqueous media and at the same time overcome aggregation problems water [8].

We report herein the synthesis and characterization of water and DMSO soluble zinc(II) phthalocyanines with octa-substituted carboxylic acid groups attached to the polyether linked triazole moieties. These novel compounds exhibit the characteristic partially-aggregated behavior by UV–vis spectra in aqueous media. Their photochemical properties, especially their singlet oxygen quantum yield, were investigated for PDT applications.

Section snippets

General

1H and 13C NMR spectra were recorded on Varian Mercury plus 300 MHz and on an Agilent-vnmrs 400 spectrometers. CDCl3, DMSO-d6 and D2O were used as the as NMR solvents. FT-IR spectra were recorded on Perkin-Elmer UATR Two spectrometer. The UV–vis absorption spectra were measured on a Shimadzu UV-1601 spectrophotometer which is double-beamed with thermostatically controlled cell block. All measurements were made in 1 mL quartz cuvette. Mass spectra were recorded on a Micromass Quattro Ultima

Results and discussions

Scheme 1, Scheme 2 describe the synthetic routes used to prepare octa-substituted non-peripheral and peripheral zinc(II) phthalocyanines. Different synthetic pathways were attempted for the synthesis of precursor compounds and metallo-phthalocyanines. The precursor compound 5 was synthesized through multistep reaction sequence (Scheme 1). The starting compound O,O'-(2,3-dicyano-1,4-phenylene) bis[dimethyl(thiocarbamate)] (3) [9] was prepared from 2,3-dicyano hydroquinone (1) and

Conclusions

In this study, symmetrically octa carboxylic acid substituted peripheral and non-peripheral zinc(II) phthalocyanines bridged with triazole attached to tetraethylene glycol linkers have been prepared as potential photosensitizers for PDT. The synthetic procedure which employs peripheral and non-peripheral alkyl sulfur donors can be used to synthesize various reactions of substitution and addition. The reaction sequence implied the preparation of 3,6-dimercapto phthalonitrile, a very important

Acknowledgements

This study was supported by TÜBİTAK. Y. Baygu acknowledges The Scientific and Technological Research council of Turkey, Ankara-Turkey for financial support in Project (Project No: 114Z441).

References (39)

  • E. Ben-Hur et al.
  • Y. Baygu et al.

    Inorg. Chem. Commun.

    (2018)
  • F. Zhang et al.

    Eur. J. Med. Chem.

    (2011)
  • A. Ogunsipe et al.

    J. Photochem. Photobiol. A: Chem.

    (2005)
  • N. Nombona et al.

    Dyes Pigm.

    (2010)
  • T.B. Ogunbayo et al.

    Polyhedron

    (2009)
  • Y. Li et al.

    Org. Biomol. Chem.

    (2015)
  • J.-Y. Jaung

    Dyes Pigm.

    (2007)
  • A. Ormond et al.

    Materials

    (2013)
  • N.B. McKeown

    Synthesis, structure and function

    Phthalocyanines Materials

    (1988)
  • M. Hu et al.

    J. Med. Chem.

    (1998)
  • A.C.H. Ng et al.

    Macromolecules

    (1999)
  • D.D. Perrin et al.

    Purification of Laboratory Chemicals

    (1980)
  • L.N. Goswami et al.

    Org. Biomol. Chem.

    (2013)
  • D. Simao et al.

    Eur. J. Inorg. Chem.

    (2001)
  • T. Furuyama et al.

    J. Am. Chem. Soc.

    (2014)
  • M. Durmuş

    Photosensitizers in medicine

  • Cited by (0)

    View full text