Synthesis of water-soluble tetra substituted metallophthalocyanines derived with quaternary amine

Phthalocyanines (Pc), among the tetrapyrol compounds, are totally synthetic products which are structurally very similar to the porphyrins such as chlorophyll and hemoglobin found in nature but can not be obtained naturally and can be synthesized as innumerable derivatives by many various methods. Coincidentally discovered phthalocyanines were first obtained by researchers A. Braun and J. Tcherniac in London in 1907 as an insoluble blue by-product during the synthesis of o-cyanobenzamide from phthalimide and acetic anhydride in alcohol at an elevated temperature. As a result of the works done by Linstead and Robertson, the structures of metal (MPc) and metal-free (H2Pc) phthalocyanines have been fully elucidated. Phthalocyanines, which are very important colorants with hues ranging from blue to yellowish green, were first introduced to the market in 1935 as the pigment of copper phthalocyanine, which has the trade name of Monastral Blue. Metal and metal-free derivatives of phthalocyanines, which can use more than 70 elements in the central cavity, have been greatly synthesized until today. A wide variety of substituents can be attached to the peripheral and non-peripheral positions of the macrocycle of phthalocyanines, the macrocyclic compounds. Various axial ligands can be attached to the central metal ion of the metallophthalocyanines. Thus phthalocyanines, which can be synthesized in very different structures and properties, are widely used in many applications in different fields. The great interest shown in phthalocyanines having many various applications such as coloring as dye and pigment, catalysis of many important reactions, detection of gas molecules as chemical sensor, treatment of cancer and other diseases in photodynamic therapy (PDT) by acting as photosensitizer, transformation of solar energy in photovoltaic cells, liquid crystal, molecular semiconductor, electrophotography, electrochromic imaging gradually increases in basic science and practice. The π conjugation through the whole ring of the 18 π electrons in the planar, symmetric, stretched, aromatic phthalocyanine macrocycle composed of four iminoisoindoline units allows the phthalocyanine compounds to exhibit a high degree of chemical and thermal stability and thus resistance to strong acids and bases. The macrocycle of phthalocyanine only decomposes in the presence of strong oxidants such as nitric acid and potassium permanganate. Phthalocyanines, which are generally obtained as four coordinated square planar geometry, can also be obtained with some metals as five coordinated square pyramidal and six coordinated octahedral geometries. Phthalocyanines usually exist in the isomorphic crystal structure. In addition to the classical phthalocyanine complexes containing four isoindole units, there are also phthalocyanine complexes in different structures such as subphthalocyanines (SubPc) which have boron in the centre and are composed of three isoindole units, superphthalocyanines (SuperPc) which have uranium in the centre and are composed of five isoindole units, sandwich complexes of lanthanide metallized bisphthalocyanines (LnPc2) and naphthalocyanines and phenanthrophthalocyanines containing units with wider π system instead of benzene units of the macrocycle. When unsubstituted phthalocyanines are not soluble, the solubility of the substituted phthalocyanines, which usually dissolve slightly in organic solvents, can be increased by the addition of bulky groups to the structure. Phthalocyanines are generally insoluble in water. Water-soluble phthalocyanines, which carry great importance for the applications in aqueous media in the fields of biology and medicine such as photodynamic cancer therapy, include cationic, anionic, zwitterionic and non-ionic substituents. When cationic substituents are groups such as quaternary ammonium and pyridinium, anionic substituents are groups such as carboxylate and sulfonate. Zwitterionic substituents such as sulfobetaine contain cationic and anionic groups and provide high solubility at high pH values or in aqueous solutions of inorganic salts such as KCl. Non-ionic substituents are groups giving solubility in water without creating an ion such as sugar derivatives (glucose, solketal) and long polymer chains (PEG). Aggregation decreasing solubility is the conversion of monomer Pc rings into dimer and oligomer forms by stacking up over and over without formation of a chemical bond. Aggregation can be inhibited by octahedral coordination of phthalocyanines or attaching bulky substituents to phthalocyanines. Firstly in this work, 4-(2-dimethylaminoethylsulfanyl)phthalonitrile ligand (1) by introducing 4-nitrophthalonitrile and 2-dimethylaminoethanethiol hydrochloride into the nucleophilic substitution reaction in the presence of K2CO3 in DMSO and copper and zinc phthalocyanines (2,4) by boiling ligand 1 with CuCl2 or Zn(CH3COO)2 salt in 2-dimethylaminoethanol at 140°C for 1 day were synthesized. Tetra peripheral 2-trimethylammoniumethylsulfanyl-substituted cationic copper and zinc phthalocyanines (3,5) were synthesized by boiling phthalocyanine 2 and 4 with methyl iodide in chloroform for 1 day. Secondly in the work, copper and zinc phthalocyanines (7,9) were synthesized by stirring 3-(2-dimethylaminoethylsulfanyl)phthalonitrile ligand (6), which was obtained by introducing 3-nitrophthalonitrile and 2-dimethylaminoethanethiol hydrochloride into the nucleophilic substitution reaction in the presence of K2CO3 in DMF, with CuCl2 or Zn(CH3COO)2 salt in 2-dimethylaminoethanol at 140°C for 1 day. Tetra non-peripheral 2-trimethylammoniumethylsulfanyl-substituted cationic copper and zinc phthalocyanines (8,10) were obtained from the boiling of phthalocyanine 7 and 9 with methyl iodide in chloroform for 1 day. In the continuation of the work, 4-nitrophthalonitrile and 2-dimethylaminoethanol formed 4-(2-dimethylaminoethoxy)phthalonitrile ligand (11) by entering into the nucleophilic substitution reaction in the presence of K2CO3 in DMSO. Copper and zinc phthalocyanines (12,14) were synthesized by boiling ligand 11 with CuCl2 or Zn(CH3COO)2 in 2-dimethylaminoethanol and at 140°C for 1 day. Tetra peripheral 2-trimethylammoniumethoxy-substituted cationic copper and zinc phthalocyanines (13,15) were synthesized by boiling phthalocyanine 12 and 14 in the presence of methyl iodide in chloroform for 1 day. In the last part of the work, 3-(2-dimethylaminoethoxy)phthalonitrile ligand (16) was obtained by introducing 3-nitrophthalonitrile and 2-dimethylaminoethanol into the nucleophilic substitution reaction in the presence of K2CO3 in DMSO. Tetra non-peripheral 2-trimethylammoniumethoxy-substituted cationic copper and zinc phthalocyanines (18,20) were formed by boiling copper and zinc phthalocyanines (17,19), which were synthesized by stirring ligand 16 with CuCl2 or Zn(CH3COO)2 in 2-dimethylaminoethanol and at 140°C during 1 day, with methyl iodide in chloroform for 1 day. Characterization of all the compounds synthesized in the study was done and their structures were proved by spectroscopic methods (FT-IR, 1H-NMR, 13C-NMR, MS (MALDI-TOF), UV-Vis). In this study, water-soluble cationic copper and zinc phthalocyanines obtained for use in biological and medical applications, such as photodynamic therapy, showed good solubility in water. Non-peripheral substituted phthalocyanines showed better solubility in water due to lower aggregation than their peripheral derivatives. The attachment of the substituents to the macrocycle via S atom or the non-peripheral positions caused the Q band to shift to red in the UV-Vis spectrum, resulting in longer wave lengths. The red shift of the Q band makes phthalocyanines more useful for the applications in the fields of biology and medicine, such as photodynamic therapy.