Biomedical Chemistry: Research and Methods, 2018, 1(3), e00042
The 40th Anniversary of the Institute of Physiologically Active Compounds of the Russian Academy of Sciences

Crown-Containing Phthalocyanines are Potential Sensibilizers for Photodynamic Therapy.
Synthesis, Properties and Role of Non-Covalent Interactions

V.E.Baulin1*, N.F.Goldshleger2, D.V. Baulin3, I.P. Kalashnikova1

1Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia;*e-mail:
2Institute of Problems of Chemical Physics of Russian Academy of Sciences, 1 Acad. Semenova av., Chernogolovka, Moscow region, 142432 Russia
3Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 31 Leninsky av., Moscow, 119071 Russia

Key words: phthalocyanines; photodynamic therapy; microheterogeneous environments; spectroscopy

DOI: 10.18097/BMCRM00042

The whole version of this paper is available in Russian.

Phthalocyanines (Pc) and their supramolecular aggregates are widely used in molecular electronics, chemical sensors, and catalysis, as well as in biology and medicine, including photodynamic therapy (PDT). One of the possibilities of preventing Pc aggregation in an aqueous medium is using surfactants: with their molecules are self-organized various supramolecular complexes. This results in formation of the required microheterogeneous Pc environment compatible with the biological medium. The monomolecular state of Pc in an aqueous medium is especially important for their use as sensitizers in fluorescence diagnostics and PDT. We have summarized here the results of investigations of distinctive features of the supramolecular aggregation of octa-[(4′-benzo-15-crown-5)oxy]phthalocyaninates (Mcr8Pc) and tetra-[(4′-benzo-15-crown-5)oxy]phthalocyaninates (Mcr4Pc) in electrolytic solutions and solutions of synthetic cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), sodium dodecylbenzenesulfonate (SDBS). Biocompatible surfactants such as carboxymethylcellulose sodium salt (Na-CMC) and sodium deoxycholate (SDC) were also studied. Using the electron absorption spectra it has been shown that formation of Mcr8Pc monomers in micellar solutions of SDC is affected by both increased surfactant concentration and by changes in the ionic strength of solution after sodium chloride is added. The effect of the chemical structure of the biocompatible anionic surfactant on monomerization of crown_containing phthalocyanines has been identified; this fact opens new possibilities for using this family of compounds for fluorescent diagnosis and PDT.

Figure 1. Structural formulas of tetra – and octa[(4’-benzo-15-crown-5)oxy]phthalocyaninates.

Figure 2. Structural formulas of surfactants.

Figure 3. Absorption spectra of aqueous solutions: (1) Cocr8Pc/5. 5•10–3 M KCl over crystalline Pc; (2) Cocr8Pc/5.5•10–3 M KCl upon diluting with water and centrifuging (7000 revolutions per minute, 04 h); and Cocr8Pc/8.6•10–3 M CTAB (3) before   and (4) after centrifugation   (7000 revolutions per minute, 04 h).

Figure 4. Absorption spectra of (1) 7.45•10–6 M Cocr8Pc and (2) 6.9•10–6 M H2cr8Pc in aqueous 5.5•10–2 M KCl solutions. Concentrations are given for the dimeric Pc forms. Insert shows the model of (Mcr8Pc)2K+8 cofacial dimer.

Figure 5. Absorption spectra of (a) (1) CTAB, (2) Cocr8Pc + CTAB, and (3) H2cr8Pc + CTAB at Cocr8Pc, H2cr8Pc, and CTAB concentrations of
1.25•10–5, 9•10–6, and 8.6•10–3 M, respectively.

Figure 6. Cocr8Pc in aqueous solutions: (1) 8.6•10–3 M CTAB; (2) 1•10–3 M CTAB +4.2•10–3 M KCl; and (3) 5.5•10–2 M KCl at Cocr8Pc concentration, M: (1, 2) 1.25•10–5 and (3) 1.3•10–5.

Figure 7. Absorption spectra of 0.67•10–5 M Cocr4Pc in (1) CH2Cl2 and (2) mixed C2H5OH + CH2Cl2 solvent at a 1:1 volume ratio of the components.

Figure 8. Absorption spectra of 0.67•10–5 M Cocr4Pc in (1) CH2Cl2 and (2–5) mixed C2H5OH + CH2Cl2 solvent at a 1:1 volume ratio of the components without CTAB and upon adding 8•10–3 M CTAB depending on the time.

Figure 9. Absorption spectra of Cocr4Pc in (1) 0.01 M and (2) 0.085 M aqueous SDS, (3) aqueous 0.0086 M CTAB, and (4) dichloromethane.

Figure 10. Absorption spectra of H2cr8Pc in (1) dichloromethane and (2, 3) aqueous solutions containing SDS : (1) [H2cr8Pc] = 5.5•10–6 M;
(2) [H2cr8Pc] = 3.66•10–5 M and [SDS] = 1.7•10–3 M;
and (3) [H2cr8Pc] = 1.1•10–5 M and [SDS] = 0.01 M.

Figure 11. Absorption spectra of (a) aqueous solutions: (1) Cocr8Pc + Na-CMC and Cocr8Pc + Na-CMC + KCl at a KCl concentration of 0.42 M.

Figure 12. Absorption spectra of Cocr8Pc + Na-CMC and (2) Cocr8Pc + Na-CMC + NaCl. The spectra were taken with respect to air, solvent is H2O, cuvette optical path is 0.2 cm.

Figure 13. Absorption spectra of Mgcr8Pc in dichloromethane (1) and a mixed solvent, C2H5OH–CH2Cl2 at the volume ratio of 1:1 (2) and 4:1 (3). The concentration of Mgcr8Pc in all these solutions is 7.7•10–6 M.

Figure 14. Absorption spectra of Mgcr8Pc: (a) in aqueous solution of SDS
(1–5) and in CH2Cl2 (6). [Mgcr8/Pc] = 8.8•10–6 and 7.7•10–6 M in the solutions of SDS and CH2Cl2, respectively, [СH3(CH2)11OSO3Na] =
0.46•10–3 (1), 1.85•10–3 (2), 5.1•10–3 (3), 6.9•10–3 (4), 9.7•10–3 (5) M;
(b) in the presence of SDS (1) and CTAB (2) in water medium,
[Mgcr8Pc] = 9.2•10–5 (1) and 1.1•10–4 M (2), [SDS] = 2.25•10–2,
[CTAB] = 8.6•10–3 M.

Figure 15. The change in the optical density of the H2cr8Pc aqueous solution (7.56•10-6 M) in the presence of SDC, SDBS and NaCl in time.
1: [SDC] = 5•10-4 M, [SDBS] = 0.014 M; 2: [SDC] = 5•10-4 M,
[SDBS] = 0.054 M; 3: [SDC] = 5•10-4 M [SDBS] = 0.054 M,
[NaCl] = 0.094 M. The decomposition into components using Gaussian functions is given under the spectral curves.

Figure 16. Changes in absorption spectra of the Mgcr8Pc/SDBS micellar solution in time under illumination.

Figure 17. Kinetics of the photobleaching of Mgcr8Pc/SDS, Mgcr8Pc/SDBS and H2cr8Pc/SDS solutions.


The work was financially supported by  Federal Agency of Scientific Organizations  (grants No. 0090-2017-0024 and No. 0081-2014-0015), Russian Academy of Sciences (program No. 34) and partially supported by the RFBR (grants No. 18-03-00743).


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