Karboran ve metalokarboran fonksiyonlu ftalosyaninler

During the past few decades there has been an increase of research into carborane derivatives. This is mainly due to their fascinating structures which make them applicable in catalysis, nonlinear optical materials, organic light emitting diodes, and boron–neutron capture therapy (BNCT) techniques. Due to its electron acceptor character, three-dimensional pseudo-aromaticity, high thermal stability, and bio-compatibility, it has several advantages as a key module in the design of new materials. Phthalocyanines have a wide application range such as dyeing, electrophotography, energy transfer, optical data storage, laser technology, etc. In addition to these areas, phthalocyanines are also used in medicinal chemistry. Over the past decades, the use of phthalocyanines as photosensitizers for photodynamic therapy of cancer (PDT) has gained a rising momentum. Phthalocyanine derivatives have stronger absorbances at longer wavelengths compared to porphyrins and most of them are capable of photoinduced singlet oxygen generation. The exciting point of phthalocyanines as photosensitizing agents is having tunable properties with the addition of substituents to the periphery of the macrocycle or axial ligands to the chelated central metal ion. Compounds containing, on one hand, polyhedral boron derivatives and, on the other hand, the phthalocyanine macrocycle are interesting as potential drugs for a combined boron neutron capture therapy of cancer (BNCT) and photodynamic therapy of cancer (PDT). Both methods are bimodal therapies for local malignant tumors. Furthermore, substitution of phthalocyanines with carborane or metallocarborane group enhances the properties of the compound as it displays a rich chemistry. The introduction of carborane groups increase solubility of phthalocyanines in most solvents. The substituted carboranes and metallocarboranes are electrochemically powerful. The redox activity of phthalocyanine may improve when it is substituted with carborane group due to the high stability, electrochemistry and ease of functionalization related to carborane. The studies carried out within the scope of this thesis can be summarized in three parts. First part examines synthesis and characterization of cobaltacarborane functionalized symmetrical and unsymmetrical phthalocyanines, second part examines synthesis and characterization of carborane functionalized symmetrical and unsymmetrical phthalocyanines. In the third part electrochemical properties is described. In the first part of this thesis, cobaltocarborane substituted phthalocyanines were synthesized. Firstly, symmetrical phthalocyanines carrying tetrakis(cobaltacarborane) units at peripheral positions were synthesized. Tetrakis(cobaltacarborane) functionalized 3Zn, 3Co and 3Mn complexes were synthesized via the nucleophilic attack of 2Zn, 2Co and 2Mn to the oxonium adduct of cobalt bis(dicarbollide). The compounds were characterized by elemental analysis, FT-IR, 1H NMR, 11B NMR, UV–Vis and mass spectrometric data. Photophysical properties of 3Zn suggest that it have potential application as dual sensitizers in the PDT and BNCT treatment of tumors. In the second study, unsymmetrical mono cobaltacarborane functionalized heptasubstituted phthalocyanines were synthesized. First, monohydroxy functionalized phthalocyanines 4Zn, 4Co and 4Mn were synthesized by mixed condensation of 4,5-bis(3-dietylaminophenoxy)phthalonitrile and 4-hydroxy phenoxyphthalonitrile in DMAE using the appropriate metal salt, namely ZnCl2, CoCl2, and MnCl2. Boronated complexes 5Zn, 5Co and 5Mn were prepared from the corresponding Pc derivatives 4Zn, 4Co and 4Mn by reaction with the oxonium derivative of cobalt bis(dicarbollide) in acetone. Structural identifications and purity of the prepared complexes were confirmed by various characterization techniques such as 1H NMR, 13C NMR , 11B NMR, UV-vis, IR, MS and elemental analysis which gave results consistent with the proposed complex structures. The electrochemical properties of these phthalocyanine conjugates were investigated. All the complexes electrochemically polymerized during anodic scan. In the last part of cobaltocarboran substituted phthalocyanines, in order to enhance the amount of boron content, we synthesized two cobaltacarborane including hexasubstituted zinc phthalocyanine together with its quaternized derivative. Similarly to the synthesis procedure of 4Zn, 6Zn was synthesized from 4,5-bis(3-dietylaminophenoxy)phthalonitrile and 4,5-dihydroxyphenoxyphthalonitrile. Boronated complex 7Zn was prepared by reaction with oxonium derivative of cobalt bis(dicarbollide) in acetone under reflux in 90 % yield. Further quaternization of the diethylamino substituents with methyl iodide yielded quaternized derivative 7ZnQ. Unfortunately, 7ZnQ was not soluble in water. In the second part of this thesis, carborane substituted phthalocyanines were synthesized. For the synthesis of the monocarborane including 9Zn, firstly alkynyl functionalized 8Zn was synthesized by mixed condensation of 4-(2-propynyloxy)-phthalonitrile and 4-[3-(diethylamino)phenoxy]phthalonitrile in DMAE in the presence of zinc chloride. The reaction of 8Zn and decaborane in a mixture of acetonitrile and toluene gave the mono-o-carboranyl-substituted phthalocyanine 9Zn in 51 % yield. The electrochemical studies showed that complex 9Zn give only ring-based redox processes. Two o-carborane including octasubstituted zinc phthalocyanine together with its quaternized derivative was synthesized in the next part. First, the alkynyl-substituted precursor, 10Zn, was prepared from 6Zn propargyl-p-toluenesulfonate via a nucleophilic substitution reaction using potassium carbonate in DMF. Using the same procedure described for 9Zn, 11Zn and decaborane in a mixture of acetonitrile and toluene gave the di-o-carboranyl-substituted 11Zn in 43 % yield. Finally, quaternization of the diethylamino substituents with methyl iodide yielded water soluble derivative 11ZnQ in 76 % yield. Structural identifications were confirmed by various characterization techniques which gave results consistent with the proposed complex structures. Carborane cages on 11ZnQ was totally transformed into nido- derivative upon standing over a period of one month in d5-pyridine including d6-DMSO. 7Zn, 7ZnQ and 11ZnQ are under investigation for BNCT applications. Octasubstituted 13Zn bearing 3-(diethylamino)phenoxy and etynylphenyl-o-carborane were synthesized using Sonogashira coupling reaction of 12Zn with a previously prepared iodinated carborane. The synthesis of 12Zn was achieved by cyclotetramerization of 4-(3-(diethylamino)phenoxy)-5-(trimethylsilyl)ethynyl phthalonitrile in DMAE and subsequently deprotection of the trimethylsilyl groups with TBAF. Sonogashira cross-coupling reaction of 12Zn with 1-p-iodophenyl-o-carborane yielded 13Zn. In the last part of the second study, we synthesized a new phthalocyanine–carborane conjugate consisting of an unsymmetrical heptasubstituted zinc phthalocyanine linked to a carboranylferrocene subunit by an arylene–alkynylene spacer. Firstly, etynyl functionalized 15Zn was carried out in two steps. 16Zn was prepared in 62% yield by Pd-catalyzed Sonogashira coupling between unsymmetrically ethynyl-substituted 15Zn and 1-p-iodophenyl-2-ferrocenyl-o-carborane. Due to the multiple bulky lipophilic groups attached at the periphery, 16Zn was very soluble in most solvents. Structural identifications and purity of the prepared complexes were confirmed by various characterization techniques such as 1H NMR, 13C NMR , 11B NMR, UV-vis, IR, MS and elemental analysis which gave results consistent with the proposed complex structures. In the last part of the study, the electrochemical properties of these phthalocyanine conjugates 3Zn, 3Co, 3Mn, 5Zn, 5Co ve 5Mn were investigated together with reference phthalocyanines. In the case of electroactive 3Co, 3Mn, 5Co and 5Mn phthalocyanine with cobaltacarborane substituents, in addition to ring based reduction, metal based reductions in both phthalocyanine core and cobaltocarborane units have been clearly identified. The electrochemical studies showed that complex 9Zn gave only ring-based redox processes.