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Macrocycles Related to Porphyrins

Through the application of previously mentioned synthetic methods, such as ‘one pot syntheses’ and ‘3+1’ condensations, many porphyrin-type macrocycles have been synthesized.

These porphyrinoids include contracted porphyrins such as triphyrin 52²⁵ and corrole,² and expanded porphyrins such as sapphyrin 53²⁶ and texaphyrin²⁷ (Figure 10).

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Figure 10 Structures of Contracted and Expanded Porphyrins

Phthalocyanines 54 are also structurally related to the porphyrins. These compounds are important synthetic pigments that are typically blue or green in color. They were first investigated by Sir Patrick Linstead, and like many other porphyrin-type structures, were found to be aromatic.

In phthalocyanine 54, each pyrrole ring is fused to a benzene ring and the pyrrole units are no longer connected by methine bridges but are instead linked by nitrogen atoms (Figure 11). Analogs of phthalocyanines have also been successfully synthesized. For instance, substitution of opposite isoindole units with benzene rings gave dicarbahemiporphyrazine 55, although this structure no longer retains aromatic properties.²⁸

Figure 11 Structures of Phthalocyanine and Dicarbahemiporphyrazine

34 Applications

Synthetic porphyrins have a variety of applications, including as ligands in metal catalyzed reactions and as photosensitizers in photodynamic therapy (PDT). By changing the chromophores in porphyrin or its analogs, the macrocycle can be tuned for use in specific applications. For instance, in PDT (a treatment for cancer), the specific properties of the photosensitizer has great significance. PDT is a multistage process. Photosensitizer administration to the patient is carried out, either systemically or topically, in the absence of light. When a sufficient amount of photosensitizer appears in the diseased tissue, it is activated by exposure to light. The light dose supplies sufficient energy to stimulate the photosensitizer and transfer the energy to molecular oxygen. This results in the generation of reactive oxygen species such as singlet oxygen. The singlet oxygen thus formed is destructive, and damages the malignant tumor cells.² Porphyrins can be used as photosensitizers in PDT because they are good at absorbing light and transferring the absorbed energy to oxygen. They are excellent candidates as photosensitizers for PDT, as they tend to accumulate in malignant cells and not healthy cells.²⁹ In PDT, porphyrins or analogues that show strong absorptions in the 650-800 nm range are preferred as photosensitizers. N-confused porphyrins, carbachlorins and oxidized carbaporphyrins, for example, tend to have strong absorptions in the far red and thus can be used for this type of application.²³

Metalloporphyrins have been widely used in asymmetric catalysis, including epoxidation,³⁰ cyclopropanation,³¹ and Suzuki-Miyaura cross coupling.³² Development of metalloporphyrins as catalysts was inspired by biological studies, such as the study of the cytochrome P450 family of monooxygenases. These enzymes contain hemes (iron porphyrins) that act as cofactors, and have been found to exhibit a broad range of functions. One of the most significant functions of this class of enzymes is the elimination of foreign molecules in the body

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through biotransformation. This family of enzymes is responsible for partial metabolism of the majority of medicines consumed by humans.³³ Another example of metalloporphyrin catalysts are manganese porphyrins absorbed on a gold surface that can react with molecular oxygen from air to carry out epoxidation of cis-stilbene to cis-stilbenoxide.

Aside from catalyzing organic reactions or being used as medicinal agents, porphyrins in the modern world can also be utilized as chemosensors for nuclear waste. Expanded porphyrin analogues have been found to bind with actinides and other heavy elements better than traditional porphyrins. These expanded macrocyclic systems can also be used for the detection of hazardous metals such as uranium or plutonium that are often used as a source for nuclear energy.³⁴

Phthalocyanines, which are closely related to porphyrin macrocycles, have also been shown to have numerous applications. They are also very stable compounds. For example, one of the first phthalocyanines characterized by Linstead was stable up to 500 °C and in the presence of concentrated sulfuric acid. Thus, these macrocycles and their analogues can be used as dyes for inks, paper, and paint and have applications as lubricants and semiconductors.²

Porphyrins and phthalocyanines have also been shown to exhibit phosphorescence and fluorescence properties.²⁸ The phosphorescence and fluorescence properties of porphyrins can be quenched by molecular oxygen. Thus, another application of porphyrins and phthalocyanines is monitoring of oxygen levels used in various arenas from ecological, industrial, and medicinal standpoints. These macrocycles can therefore serve the purpose of optical sensors for molecular oxygen.²⁸ The concentration of molecular oxygen in the gas or liquid phase is proportional to the decay of phosphorescence in the porphyrin and phthalocyanine.²⁸ The most common porphyrin optical sensors are palladium(II) and platinum(II) metalloporphyrins. In addition, ruthenium(III) and iridium(III) metalloporphyrins have also exhibited high phosphorescence at room temperature

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and could possibly be used as alternative oxygen sensors in the near future.²

Carbaporphyrins

In order to gain a better understanding of the reactivity and characteristics of porphyrins, chemists began to investigate core modified porphyrins. The study of core modified porphyrins helps to reveal the effect that modification of a conjugated system has on its properties and its characteristics. Systems with a carbon atom inserted into the core of the porphyrin, the so-called carbaporphyrinoid systems, have been of particular interest. These systems have been widely investigated and have shown unique properties, such as formation of organometallic derivatives under mild conditions.³⁵ Related systems include N-confused porphyrin 56,³⁶ benzocarbaporphyrins 57,³⁵ tropiporphyrins 58,³⁷ azuliporphyrins 59³⁸ and benziporphyrin 60³⁹ (Figure 12).³⁵

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Figure 12 Monocarbaporphyrin Analogues

These porphyrin analogues can be subdivided into “true” carbaporphyrins and “modified”

carbaporphyrins. In true carbaporphyrins, at least one of the pyrrolic units is replaced with a cyclopentadiene or indene unit. In modified carbaporphyrins, a carbocyclic ring system other than a cyclopentadiene unit is used to replace a pyrrole moiety.³⁵ For instance, by replacing a pyrrolic unit within the porphyrin framework with azulene, cycloheptatriene, or benzene, new families of porphyrin-like macrocycles were produced. True carbaporphyrins such as benzocarbaporphyrin 57 are fully aromatic structures, while benziporphyrins 60 do not have aromatic character, and azuliporphyrins 59 fall midway between the two extremes.³⁵

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In benzocarbaporphyrins 57, porphyrin-like UV−vis spectra are retained and these compounds are highly diatropic, as judged by proton NMR spectroscopy. However, azuliporphyrins 59 are cross-conjugated and have considerably reduced diatropic character, while tropiporphyrins 58 have intermediary properties due to the nonplanar nature of the seven-membered ring.³⁵ In principle, if more than one nitrogen atom in the cavity is replaced with carbon atoms, this results in the formation of dicarbaporphyrins, tricarbaporphyrins and tetracarbaporphyrins (Figure 13).⁴¹

Figure 13 Mono-, Di-, Tri- and Tetracarbaporphyrins

Carbaporphyrins can easily be synthesized by the “3+1” condensation approach.¹⁶ One of the best studied classes of carbaporphyrins are the benzocarbaporphyrins. In benzocarbaporphyrins 57, one of the pyrrole units is replaced with an indene unit. These compounds are prepared by the acid catalyzed condensation of indene dialdehyde 61 with tripyrrane 62 (Scheme 17)⁴⁰. Following

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oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), carbaporphyrin 57 was isolated in > 40% yield.