Classic highlights in porphyrin and porphyrinoid total synthesis and biosynthesis

Porphyrins feature prominently in nature, be it as enzymatic cofactors, electron and exciton shuffles, as photoactive dyes, or as signaling substances. Their involvement in the generation, storage and use of oxygen is pivotal to life, while their photochemical properties are central to the biochemical functioning of plants. When complexed to metals, porphyrins can engage in a multitude of contemporary applications ranging from solar energy generation to serving as catalysts for important chemical reactions. They are also able to function as useful theranostic agents, and as novel materials for a wide range of applications. As such, they are widely considered to be highly valuable molecules, and it almost goes without saying that synthetic organic chemistry has dramatically underpinned all the key advances made, by providing reliable access to them. In fact, strategies for the synthesis of functionalized porphyrins have now reached a state of refinement where pretty well any desired porphyrin can successfully be synthesized with the approaches that are available, including a cornucopia of related macrocycle-modified porphyrinoids. In this review, we are going to illustrate the development of this exciting field by discussing a number of classic syntheses of porphyrins. Our coverage will encompass the natural protoporphyrins and chlorophylls, while also covering general strategies for the synthesis of unsymmetrical porphyrins and chlorins. Various industrial syntheses of porphyrins will also be discussed, as will other routes of great practical importance, and avenues to key porphyrinoids with modified macrocycles. A range of selected examples of contemporary functionalization reactions will be highlighted. The various key syntheses will be described and analyzed from a traditional mechanistic organic chemistry perspective to help student readers, and those who are new to this area. The aim will be to allow readers to mechanistically appreciate and understand how many of these fascinating ring-systems are built and further functionalized

Lead Structures for Applications in Photodynamic Therapy. 6. Temoporfin Anti-Inflammatory Conjugates to Target the Tumor Microenvironment for In Vitro PDT

Due to the ongoing development of clinical photodynamic therapy (PDT), the search continues for optimized photosensitizers that can overcome some of the side effects associated with this type of treatment modality. The main protagonists being: post-treatment photosensitivity, due to only limited cellular selectivity and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory agents within the tumor microenvironment. A photosensitizer that could overcome one or both of these drawbacks would be highly attractive to those engaged in clinical PDT. Certain non-steroidal anti-inflammatory drugs (NSAIDs) when used in combination with PDT have shown to increase the cytotoxicity of the treatment modality by targeting the tumor microenvironment. Temoporfin (m-THPC), the gold standard chlorin-based photosensitizer (PS) since its discovery in the 1980’s, has successfully been conjugated to non-steroidal anti-inflammatory compounds, in an attempt to address the issue of post-treatment tumor regrowth. Using a modified Steglich esterification reaction, a library of “iPorphyrins” was successfully synthesized and evaluated for their PDT efficacy

Effects of Preparation Conditions of Poly(lactide-co-glycolide) Nanoparticles Loaded with Amphiphilic Porphyrins and Their Photoactivities

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Three porphyrins, (5,10,15,20-tetra(3-hydroxyphenyl) porphyrin, 5-hexyl-10,20-bis(3-hydroxyphenyl)porphyrin and 5-hexyl-10,15,20-tris(3-hydroxyphenyl) porphyrin), with different amphiphilicities and equal singlet oxygen quantum yields in ethanol, were encapsulated into 50: 50 poly(lactide-co-glycolide), nanoparticles prepared by the emulsion/evaporation technique. A 2(2) factorial design was utilized to evaluate the influence of the porphyrin/polymer mass ratio and the percentage of ethanol in the aqueous phase on the size and zeta potential of the nanoparticles. Increasing both the amount of ethanol and the porphyrin/polymer ratio decreases the size and increases zeta potential for the photosensitizers studied, except for 5-hexyl-10,15,20-tri(3-hydroxyphenyl) porphyrin. Entrapment efficiency depended on the individual m-hydroxyphenylporphyrin and ranged from 69 to 97%. After 1.5 h incubation with m-hydroxyphenylporphyrin-loaded nanoparticles the percentages of intracellular uptake were the same for all porphyrins since the molecules are confined in the nanoparticles, hampering the interaction of the amphiphilic photosensitizers with the cellular membrane. All encapsulated porphyrins caused the same decrease of cell viability and always localized in the perinuclear region of the cells. Results show that these m-hydroxyphenylporphyrins, although with different amphiphilicities, have equal photodynamic efficacies.14862746286Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Health Research BoardConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Synthesis and electrochemical investigation of covalently linked porphyrin dimers containing a beta-brominated subunit. Crystal structure of H-2[tripp-tpp(Br-8)]H-2

Ten meso-tetraphenylporphyrin-type heterodimers containing a partly or completely beta-brominated subunit were synthesized and characterized by UV-visible spectroscopy, cyclic voltammetry and spectroelectrochemistry, showing the presence of low electronic interactions between the two subunits. The investigated compounds are represented as M[(tripp-tpp(Br-4)]M and M[tripp-tpp(Br-8)]M (M = 2H, Zn, Ni, Co and Cu) where tripp-tpp(Br-4) is the tetraanion of 1-[5-(10,15,20-triphenylporphyrinyl)]-4-[10-(2,3,12,13-tetrabromoporphyrinyl)]-benzene and tripptpp(Br-8) is the tetraanion of 1-[5-(10,15,20-triphenylporphyrinyl)]-4-[10-(2,3,7,8,12,13,17,18-octabromoporphyrinyl)] -benzene. One of the synthesized dimers, H-2[tripp-tpp(Br-8)]H-2, was characterized by a single-crystal X-ray investigation. Copyright (C) 2003 Society of Porphyrins & Phthalocyanines

Synthesis and biological evaluation of Foscan® bile acid conjugates to target esophageal cancer cells.

Porphyrins and chlorins such as Foscan® have a natural proclivity to accumulate in cancer cells. This trait has made them good candidates for photosensitizers and as imaging agents in phototherapy. In order to improve on cellular selectivity to lower post-treatment photosensitivity bile acid porphyrin bioconjugates have been prepared and investigated in esophageal cancer cells. Bile acids which are known to selectively bind to, or be readily taken up by cancer cells were chosen as targeting moieties. Synthesis of the conjugates was achieved via selective nucleophilic monofunctionalization of 5,10,15,20-tetrahydroxyphenylporphyrins with propargyl bromide followed by Cu(I) mediated cycloaddition with bile acid azides in good yields. The compounds were readily taken up by esophageal cancer cells but showed no PDT activity