Porphyrin and phthalocyanine photosensitizers designed for targeted photodynamic therapy of colorectal cancer.

Colorectal cancer is of particular concern due to its high mortality rate count. Recent investigations on targeted phototherapy involving novel photosensitizers and drug-delivery systems have provided promising results and realistic prospects for a successful medical treatment. New research trends have been focused particularly on development of advanced molecular systems offering effective photoactive species which could be selectively delivered directly into the affected cells. Porphyrins and phthalocyanines have been considered extremely attractive for this purpose due to their molecular versatility, excellent photochemical properties and multifunctional nature. In this review it has been demonstrated that such macrocyclic compounds may effectively contribute to the inhibition of the growth of colon cancer cells and eventually to their photonecrosis. Purposely designed and tailored porphyrin and phthalocyanine derivatives in combination with smart drug-carriers have proved suitable for photodynamic therapy (PDT) and related antitumor treatments. This survey comprises a choice of potentially applicable ideas developed since 2010 involving 9 different tumor cell lines and featuring 32 photosensitizers.

Hydrogen Bond-Mediated Conjugates Involving Lanthanide Diphthalocyanines and Trifluoroacetic Acid (Lnpc2@TFA): Structure, Photoactivity, and Stability.

The interaction between lanthanide diphthalocyanine complexes, LnPc2 (Ln = Nd, Sm, Eu, Gd, Yb, Lu; Pc = C32H16N8, phthalocyanine ligand) and trifluoroacetic acid (TFA) was investigated in benzene, and the stability of the resulting molecular system was assessed based on spectral (UV-Vis) and kinetic measurements. Structural Density Functional Theory (DFT) calculations provided interesting data regarding the nature of the bonding and allowed estimating the interaction energy between the LnPc2 and TFA species. Conjugates are created between the LnPc2 and TFA molecules via hydrogen bonds of moderate strength (>N∙∙H··) at the meso- -bridges of the Pc moieties, which renders the sandwich system to flatten. Attachment of TFA is followed by rearrangement of electronic density within the chromophore system of the macrocycles manifested in considerable changes in their UV-Vis spectra and consequently the color of the studied solutions (from green to orange). The LnPc2@TFA conjugates including Nd, Sm, Eu, and Gd appeared evidently less photostable when exposed to UV radiation than the related mother compounds, whereas in the case of Yb and Lu derivatives some TFA-prompted stabilizing effect was noticed. The conjugates displayed the capacity for singlet oxygen generation in contrast to the LnPc2s itself. Photon upconversion through sensitized triplet-triplet annihilation was demonstrated by the TFA conjugates of Nd, Sm, Eu, and Gd.

The effect of organic solvents on selected microorganisms and model liposome membrane.

The effect of methanol, ethanol, acetone, N,N-dimethylformamide (DMF), dimethyl sulfoxide and Nujol on the growth of Escherichia coli DH5α, Bacillus subtilis and Saccharomyces cerevisiae D273 was investigated. All of the tested cultures appeared susceptible to the organic media they were treated with, which evinced in apparent hindering of cell development. The observed diverse solvent tolerance, except from their different biochemical activity, may also be related to the changes in cell membrane fluidity induced by the solvent species. Parallel electron paramagnetic resonance investigations using egg yolk lecithin model liposomes revealed that the fluidity of the phospholipid system in cell membranes may either be considerably decreased (Nujol, DMF, ethanol) or increased (acetone), thus rendering difficult the intracellular nutrient supply. Hence, even the chemically neutral Nujol produced a distinct cell-growth inhibitory effect. These results are fairly consistent with the outcome of the survival tests, particularly for the bacteria strains.

Liposomes modified by mono- and bis-phthalocyanines: A comprehensive EPR study.

The impact of selected metallophthalocyanines, featuring diverse molecular structure, upon the fluidity of liposome membranes was studied using the spin label EPR technique. The "mono"-type MPc's (M = Zn, Sn; Pc = C32H16N8 is the phthalocyanine ligand) and sandwich LnPc2 complexes (Ln = Nd, Sm, Gd) were explored. Liposomes were obtained in a sonication process, from egg yolk lecithin (EYL) in water. TEMPO and 16-DOXYL spin labels were used to monitor the peripheral and central part of the lipid double layer, respectively, which allowed to localize the phthalocyanine additive within the bilayer, as well as to perform independent measurements of changes in fluidity upon addition thereof. All the complexes tested were found to increase the fluidity in the middle of the lipid bilayer. However, at the water-lipid interface the LnPc2 compounds showed a relative small effect upon the phospholipids' arrangement, whereas in the case of ZnPc and SnPc it was found much more pronounced. EPR results were supplemented by measurements of static electrical charge, the investigated phthalocyanines may potentially feed into the membrane thus affecting its stability.

Novel lipophilic lanthanide bis-phthalocyanines functionalized by pentadecylphenoxy groups: synthesis, characterization and UV-photostability.

Novel sandwich-type phthalocyanines containing a rare earth metal core (Pr, Nd, Eu-Lu) and macrocycles peripherally substituted by pentadecylphenoxy groups were synthesized using a cardanol-based phthalonitrile precursor and the respective lanthanide acetate. Additionally, the metal free-base analog compound was studied for comparison. The purified reaction products were all found to be thick and viscous substances at room temperature, showing liquid crystalline behavior with a distinct increase in fluidity at ca. 40 ° C. The complexes are readily soluble in chloroalkyl solvents and dissolve fairly well in DMF with some tendency to form aggregates. Besides they are strongly hydrophobic and reveal a peculiar affinity for lipophilic media. The compounds have been characterized by UV-Vis (absorption and emission), FTIR, MS and DSC methods. Photochemical activity in the liquid phase (dimethylformamide, dichloromethane, mineral oil) and the degree of photodegradation demonstrated under constant UV-irradiation (λ = 352 nm) have been analyzed and discussed in terms of photostability.

Photocatalytic activity of nano and microcrystalline TiO(2) hybrid systems involving phthalocyanine or porphyrin sensitizers.

Hybrid photocatalysts based on TiO(2)-anatase matrix, representing the both micro- and nano-structures, impregnated with selected lanthanide diphthalocyanine and metalloporphyrin sensitizers, were compared to evaluate their activity and effectiveness in a water suspension catalytic system designed to degrade 4-nitrophenol (4-NP) in a UV-stimulated reaction. Either type of the anatase catalyst was proved to be effective in mineralizing of 4-NP. However, kinetic studies confirmed that the composite's efficiency basically depends on the nature of the macromolecular sensitizer and to a minor extent on the dimensions (micro/nano) of the TiO(2) particles. The apparent higher activity observed for the micro-TiO(2) catalysts indicates improvement of the electron transfer between the sensitizer and the micro-crystalline structure of TiO(2)-anatase in contrast to the nano-crystalline matrix. The mechanistic aspects of the observed catalytic performances have been discussed.

Structural and molecular characterization of meso-substituted zinc porphyrins: a DFT supported study.

Structural parameters of a range of over 100 meso-substituted zinc porphyrins were reviewed and compared to show how far the nature of the functional group may affect the interatomic distances and bond angles within the porphyrin core. It was proved that even despite evident deformations of the molecular structure, involving twisting of the porphyrin's central plane, the coupled π-bonding system remains flexible and stable. DFT calculations were applied to a number of selected porphyrins representative for the reviewed compounds to emphasize the relevance of theoretical methods in structural investigations of complex macrocyclic molecular systems. Experimental and DFT-simulated IR spectral data were reported and analyzed in context of the individual molecular features introduced by the meso substituents into the porphyrin moiety base. Raw experimental spectral data, including ¹H- and ¹³C-NMR, UV-Vis, FTIR, XRD, and other relevant physicochemical details have been provided for a specially chosen reference zinc porphyrin functionalized by tert-butylphenyl groups.

UV photostability of metal phthalocyanines in organic solvents.

Kinetic studies of photochemical reactions induced by UV radiation in solutions of metal phthalocyanines have been carried out to determine the factors which might have influenced the stability of photosensitized phthalocyanines. Complexes of the molecular type Mpc, M'(2)pc, and Lnpc(2) (where M = Li, Mg, Fe, Co, Zn, Pb; M'= Tl; Ln = rare earth; pc = phthalocyanine ligand, C(32)H(16)N(8)(2-)) were investigated in DMF, DMSO, and pyridine. Progressive decay of the phthalocyanine macrocycle due to absorption of UV light was observed. Phthalimide found in the final photolysis product may indicate some chemically bonded oxygen involved in the solid phthalocyanine material. Fluorescence lifetimes determined for the studied compounds (2.91-5.98 ns) have shown no particular relation to the stability of the excited macrocyclic system. The bonding strength of the photosensitized phthalocyanine moiety appears to rely on typical chemical factors, rather than on the properties of the excited states. Kinetics of the degradation process has proved to depend on the molecular structure of the complex and seems to be controlled by interactions of the macrocycle bridging nitrogen atoms with the solvent molecules. The use of electron acceptor solvents such as DMSO may enhance the molecular stability of phthalocyanines excited by UV radiation. Sandwich-type rare earth diphthalocyanines dissolved in DMSO displayed the highest photostability.