Porphyrin Isomers Research Articles

Metalloporphycene is an Attractive Cofactor for Hemoproteins

Abstract Porphycene, a constitutional isomer of porphyrin, is an attractive ligand, and its metal complexes have been investigated as alternative metal cofactors for hemoproteins such as myoglobin. Iron, cobalt and manganese complexes of porphycene are smoothly inserted into apomyoglobin after removal of native heme b, resulting in stable reconstituted proteins. Myoglobin reconstituted with iron porphycene exhibits extremely high O2 affinity compared to native myoglobin (nMb). In addition, the reconstituted protein also shows catalytic activity toward one-electron oxidation of phenol derivatives and sulfoxidation of thioanisole, although the natural function of nMb is O2 storage. Furthermore, myoglobin reconstituted with manganese porphycene can promote H2O2-dependent hydroxylation of inert alkane species as seen with cytochrome P450s. Myoglobin reconstituted with iron porphycene can act as a catalyst for abiological reactions such as cyclopropanation with ethyl diazoacetate. These results clearly indicate that replacement of heme with metalloporphycenes can dramatically alter the function of hemoproteins.

Doubly N-confused and ring-contracted [24]hexaphyrin Pd-complexes as stable antiaromatic N-confused expanded porphyrins

As isomers of the regular porphyrins, N-confused porphyrins have attracted extensive attention of chemists because of their unique chemical structures, chemical reactivities, and physical properties, which result in their promising applications in the fields of catalytic chemistry, biochemistry and material science. Typically, N-confused porphyrins are synthesized via acid catalyzed condensation and following oxidation during which lactams are often formed as the byproducts. Here we report doubly N-confused and ring-contracted [24]hexaphyrin(1.1.0.1.1.0) mono- and bis-Pd-complexes as stable antiaromatic N-confused expanded porphyrins, which are synthesized through Pd-catalyzed Suzuki-Miyaura coupling of 1,14-dibromotripyrrin. These macrocycles show a paratropic ring currents, an ill-defined Soret band, a red-shifted weak absorption tail, and a small HOMO-LUMO gap. NBS bromination of the bis Pd-complex give its mono- and dibromides regioselectively, which are effectively used to synthesize a [24]hexaphyrin dimer and a NiII porphyrin-[24]hexaphyrin-NiII porphyrin triad, respectively.

Coupling between tautomerism and radiationless deactivation in porphycenes

Abstract Quantum yields of fluorescence of porphycenes – porphyrin isomers – can vary by orders of magnitude, even for very similar derivatives, such as meso-dimethyl- vs. meso-tetramethylporphycene. In weakly emitting porphycenes the fluorescence intensity strongly depends on viscosity and can be recovered by placing a molecule in a rigid environment. We postulate that the efficient nonradiative deactivation is due to the quantum effect, delocalization of the inner protons. The delocalization, which increases with the strength of intramolecular hydrogen bonds may induce structural changes that lead to distortion from planarity and, as a result, efficient S0 ← S1 internal conversion. The effect seems to be general, as indicated by good correlation between the quantum yield of fluorescence and the distance between H-bonded nitrogen atoms, the latter being a reliable measure of hydrogen bonding strength. Based on the available photophysical and X-ray data, such correlation was found so far for over 20 differently substituted porphycenes.

Review on N-confused porphyrin

We all know how vital porphyrin is to our body, from binding haemoglobin and iron to carrying oxygen to our organs and tissues. Recently, there has been a discovery about a new isomer of porphyrin called N-confused porphyrin. Its chemistry is very different and exciting. From there, scientists have explored many corners of this confusion chemistry, from doubly confused coordination to its supramolecular architecture, it has an identical backbone structure as porphyrin (1,1,1,1). NCP, on the other hand, has an additional pyrrolic moiety called a "confused pyrrole" that is linked to the surrounding meso-carbons at the α and β-positions. The position of pyrrolic N-H and β-CH are shifted as a result of this unusual linkage. Resulting, NCP contains an NNNC core and an outward-pointing N atom. When a metal is co-ordinated in the core, a kind of organometallic complex having a carbon-metal bond is formed. On the other hand, the peripheral nitrogen atom serves as a H-bonding donor/acceptor and a metal coordination site.

Energy Relaxation of Porphycene in Atomic and Molecular Cryogenic Matrices

The kinetics of relaxation of high-lying electronic states of porphycene (porphyrin isomer) embedded in different cryogenic matrices were studied using picosecond time-resolved fluorescence (TRF) and transient absorption (TA) techniques. The molecule was excited into the Soret band, i.e., with a large energy excess compared to that of the lowest (Q) excited state. The TRF and TA time profiles obtained for porphycene embedded in argon and methane matrices were remarkably different: the overall relaxation in argon occurred in 64 ps, whereas the corresponding value for methane matrix was 18 ps. Analysis of the evolution over time of different spectral ranges of TRF spectra indicates the multidimensional character of relaxation kinetics.

Phosphorescence and Photophysical Parameters of Porphycene in Cryogenic Matrices

Matrix isolation studies were carried out for porphycene, an isomer of porphyrin, embedded in solid nitrogen and xenon. The external heavy atom effect resulted in nearly a 100% population of the triplet state and in the appearance of phosphorescence, with the origin located at 10163 cm−1. This energy is much lower than that corresponding to the T1 position in porphyrin. This difference could be explained by postulating that the orbital origin corresponds in both isomers to the second excited singlet state, which lies much closer to S1 in porphycene. Most of the vibrational frequencies observed in the phosphorescence spectrum correspond to totally symmetric modes, but several ones were assigned to the out-of-plane Bg vibrations. These bands are not observed in fluorescence, which suggests their possible role in vibronic-spin-orbit coupling.

EP018: Late-onset congenital erythropoietic porphyria associated with myeloid malignancy

Congenital erythropoietic porphyria (CEP, OMIM #263700) is a rare disorder of heme biosynthesis characterized biochemically by elevated excretion of type I porphyrin isomers in urine and feces. The disorder is caused by decreased uroporphyrinogen III synthase (UROS) activity, leading to an overproduction of the dead-end metabolites uro- and coproporphyrinogen I, primarily in the bone marrow, and the subsequent deposition of type I porphyrin isomers in tissues.

Porphyrin induced structural destabilization of a parallel DNA G-quadruplex in human MRP1 gene promoter.

Porphyrins are among the first ligands that have been tested for their quadruplex binding and stabilization potential. We report the differential interaction of the positional cationic porphyrin isomers TMPyP3 and TMPyP4 with a parallel G-quadruplex (GQ) formed by 33-mer (TP) regulatory sequence present in the promoter region of the human multidrug resistance protein 1 (MRP1) transporter gene. This GQ element encompasses the three evolutionary conserved SP1 transcription factor binding sites. Taking into account that SP1 binds to a non-canonical GQ motif with higher affinity than to a canonical duplex DNA consensus motif, it is suggestive that GQ distortion by cationic porphyrin will have important implications in the regulation of MRP1 expression. Herein, we employed biophysical analysis using circular dichroism, visible absorption, UV-thermal melting and steady-state fluorescence spectroscopy, reporting destabilization of MRP1 GQ by cationic porphyrins. Results suggest that TMPyP4 and TMPyP3 interact with GQ with a binding affinity of 106 to 107 M-1 . Thermodynamic analysis indicated a significant decrease in melting temperature of GQ (ΔTm of 15.5°C-23.5°C), in the presence of 2 times excess of porphyrins. This study provides the biophysical evidence indicating the destabilisation of a parallel DNA G-quadruplex by cationic porphyrins.

Hydrogen Bond Engineering Visualized by Picometer-Level Distortion of Planar Porphyrin Isomers.

Directly investigating hydrogen bond (HB) dynamics in molecular materials is a challenging task. Here, we report a set of porphyrin isomers, porphycenes, that visualize slight changes on the order of picometers in the intramolecular HB dynamics. Intramolecular HBs of porphycenes were regulated by the systematic modification at meso positions with methyl (Me), cyclopentyl (Cy5), and cyclohexyl (Cy6) moieties. Notably, the quantum yields varied from 35 to 0.04% in chloroform, depending on a slight distortion in the porphycene framework. SC-XRD, XPS, and NMR clearly revealed that the Me and Cy6 moieties increased the nonradiative deactivation by strengthening the intramolecular NH···N HBs whereas Cy5 retained their photoluminescence properties. This is the first example of how the distortion of planar porphyrinoids at the picometer level along with the strength of the intramolecular NH···N HBs can drastically affect their optical properties. The results revealed new avenues of HB engineering based on porphyrinoids.

Exploring manganese pyridylporphyrin isomers for cyclohexane oxidation: First‐generation catalysts are better than third‐generation ones

AbstractManganese porphyrins are widely studied as catalysts for oxidation reactions of different organic substrates. In this work, we evaluate the catalytic activity of manganese complexes derived from meso‐tetrakis(2‐, 3‐, or 4‐pyridyl) porphyrin isomers, [Mn(TXPyP)]Cl (X = 2, 3, or 4), and the respective β‐octabrominated counter‐parts, [Mn(Br8TXPyP)], for oxidation of cyclohexane by PhI(OAc)2. At first, we describe the synthesis and characterization of a new third‐generation manganese porphyrin, [Mn(Br8T4PyP)]. It presented a more positive value of half‐wave potential (−0.287 V vs. Fc+/Fc) and a lower solubility in organic solvents among the isomers. In general, the third‐generation catalysts [Mn(Br8TXPyP)] showed lower catalytic activity than those of the first‐generation [Mn(TXPyP)]Cl in all systems studied. In addition, the use of water or imidazole as cocatalysts did not increase the yield or selectivity of the systems. Finally, when evaluating the use of the classic oxidant PhIO, there was a decrease in yield for all systems, indicating that PhI(OAc)2 is a good substitute for this oxidant in catalytic systems.

Neo-Porphyrinoids: New Members of the Porphyrinoid Family.

The four pyrrole rings and four meso carbons of tetrapyrrolic porphyrins can be arranged in different ways and the resulting porphyrin isomers exhibit very distinct electronic properties. The extensive research carried out on the porphyrins over the years has revealed that porphyrin can have several possible isomers and some of these have been identified and synthesized. Among the porphyrin isomers synthesized so far, porphycene and N-confused porphyrins have been investigated extensively whereas the other porphyrin isomers such as hemiporphycene, corrphycene and isoporphycene remain underdeveloped because of synthetic difficulties and their inherently unstable nature. Neoporphyrinoids are new members of the porphyrinoid family that were discovered serendipitously in 2011. Neoporphyrinoids are structural analogues of porphyrinoids with a confused pyrrole nitrogen linked to a meso carbon or the adjacent pyrrole carbon. Thus, neoporphyrinoids have an unusual structure in which pyrrole N is a part of a porphyrinoid framework and the lone pair of electrons on nitrogen participate in macrocyclic conjugation. It's been a decade since the discovery and different types of neoporphyrinoids, including regular, contracted and expanded neoporphyrinoids, have been synthesized by rational synthetic methodologies and their spectral, structural, aromatic and coordination properties have been studied. There is huge scope to develop different synthetic routes to produce new types of stable neoporphyrinoids to study their properties and potential applications. This article presents a brief overview of the synthesis, structure and properties of the neoporphyrinoids reported in this decade.

Substituent screening effect on single-molecule photostability: comparison of three differently substituted porphycenes

Photobleaching of single molecules has been studied using confocal fluorescence microscopy for porphycene, a porphyrin isomer, and its two derivatives. Fourfold substitution of porphycene with bulky tert-butyl groups leads to the enhancement of photostability, even though the spectral, photophysical, and redox parameters remain similar. We attribute this effect to the increase of the efficiency of physical quenching of the chromophore triplet state by oxygen, compared with the yield of chemical reaction that leads to photobleaching. Analysis of the observed photon fluxes from single emitters embedded in a polymer film shows that the experiment based on fluorescence is biased towards detection of molecules which have oxygen—the triplet quencher—in their vicinity. The distribution of the measured photodegradation quantum yields is very heterogeneous, suggesting that physical and chemical quenching rates exhibit different distance and orientation dependences.

Controlling Emissive Properties by Intramolecular Hydrogen Bonds: Alkyl and Aryl meso-Substituted Porphycenes.

Porphycene, a porphyrin isomer, is an efficient fluorophore. However, four-fold meso substitution with alkyl groups decreases the fluorescence quantum yield by orders of magnitude. For aryl substituents, this effect is small. To explain this difference, we have synthesized and studied a mixed aryl-alkyl-substituted compound, 9,20-diphenyl-10,19-dimethylporphycene, as well as the 9,20-diphenyl and 9,20-dimethyl derivatives. Analysis of the structural, spectroscopic, and photophysical data of the six porphycenes, combined with quantum chemical calculations, shows a clear correlation between the strength of the intramolecular NH⋅⋅⋅N hydrogen bonds and the efficiency of the radiationless depopulation of the lowest-excited singlet state. This result led us to propose a model in which the delocalization of the inner protons in the cavity of the macrocycle is responsible for the nonradiative deactivation channel. The applicability of the model is confirmed by the literature data for other alkyl- or aryl-substituted porphycenes. The finding of a correlation between structural and emissive characteristics enables a rational design of porphycenes with desired photophysical properties.

Iron chelation rescues hemolytic anemia and skin photosensitivity in congenital erythropoietic porphyria

AbstractCongenital erythropoietic porphyria (CEP) is an inborn error of heme synthesis resulting from uroporphyrinogen III synthase (UROS) deficiency and the accumulation of nonphysiological porphyrin isomer I metabolites. Clinical features are heterogeneous among patients with CEP but usually combine skin photosensitivity and chronic hemolytic anemia, the severity of which is related to porphyrin overload. Therapeutic options include symptomatic strategies only and are unsatisfactory. One promising approach to treating CEP is to reduce the erythroid production of porphyrins through substrate reduction therapy by inhibiting 5-aminolevulinate synthase 2 (ALAS2), the first and rate-limiting enzyme in the heme biosynthetic pathway. We efficiently reduced porphyrin accumulation after RNA interference–mediated downregulation of ALAS2 in human erythroid cellular models of CEP disease. Taking advantage of the physiological iron-dependent posttranscriptional regulation of ALAS2, we evaluated whether iron chelation with deferiprone could decrease ALAS2 expression and subsequent porphyrin production in vitro and in vivo in a CEP murine model. Treatment with deferiprone of UROS-deficient erythroid cell lines and peripheral blood CD34+-derived erythroid cultures from a patient with CEP inhibited iron-dependent protein ALAS2 and iron-responsive element–binding protein 2 expression and reduced porphyrin production. Furthermore, porphyrin accumulation progressively decreased in red blood cells and urine, and skin photosensitivity in CEP mice treated with deferiprone (1 or 3 mg/mL in drinking water) for 26 weeks was reversed. Hemolysis and iron overload improved upon iron chelation with full correction of anemia in CEP mice treated at the highest dose of deferiprone. Our findings highlight, in both mouse and human models, the therapeutic potential of iron restriction to modulate the phenotype in CEP.

3,6,13,16-Tetrasubstituted Porphycene: The Missing Link in Porphycene Chemistry.

We have introduced the first 3,6,13,16-tetrasubstituted porphycene as its tetramethoxy analogue. This substitution pattern is one of the most general patterns yet missing in this isomeric porphyrin chemistry. This porphycene exhibits intense fluorescence along with the ability to coordinate with divalent metal ions; in particular, it forms the first stable Zn(II) complex among the tetrasubstituted porphycenes. Notably, the molecular structure of Zn1•Py displays supramolecular chirality.

Cover Feature: A Mechanistic Dichotomy in Two‐Electron Reduction of Dioxygen Catalyzed by N,N’‐Dimethylated Porphyrin Isomers (Chem. Eur. J. 46/2020)

Selective two-electron reduction of O2 to H2O2 has been achieved by nonplanar N,N’-dimethylated porphyrin isomers as organocatalysts, showing the highest TON among homogeneous metal-free catalysts. Hydrogen bonding between pyrrolic protons of reduced porphyrinoids and O2 plays an important role to control the reaction mechanism in catalytic O2 reduction. The cover art describes different mechanisms of the O2 reduction by the two isomers on the background showing shining Mt. Tsukuba in the sunset. More information can be found in the Full Paper by T. Kojima et al. on page 10480.

A Mechanistic Dichotomy in Two‐Electron Reduction of Dioxygen Catalyzed by N,N’‐Dimethylated Porphyrin Isomers

Selective two-electron reduction of dioxygen (O2 ) to hydrogen peroxide (H2 O2 ) has been achieved by two saddle-distorted N,N'-dimethylated porphyrin isomers, an N21,N'22-dimethylated porphyrin (anti-Me2 P) and an N21,N'23-dimethylated porphyrin (syn-Me2 P) as catalysts and ferrocene derivatives as electron donors in the presence of protic acids in acetonitrile. The higher catalytic performance in an oxygen reduction reaction (ORR) was achieved by anti-Me2 P with higher turnover number (TON=250 for 30 min) than that by syn-Me2 P (TON=218 for 60 min). The reactive intermediates in the catalytic ORR were confirmed to be the corresponding isophlorins (anti-Me2 Iph or syn-Me2 Iph) by spectroscopic measurements. The rate-determining step in the catalytic ORRs was concluded to be proton-coupled electron-transfer reduction of O2 with isophlorins based on kinetic analysis. The ORR rate by anti-Me2 Iph was accelerated by external protons, judging from the dependence of the observed initial rates on acid concentrations. In contrast, no acceleration of the ORR rate with syn-Me2 Iph by external protons was observed. The different mechanisms in the O2 reduction by the two isomers should be derived from that of the arrangement of hydrogen bonding of a O2 with inner NH protons of the isophlorins.

Rectangular Holes in Porphyrin Isomers Act As Mono- and Binucleating Ligands: Stereochemistry of Mono- and Diboron Porphycenes and Their Protonation Behaviors.

The first boron complexes of porphycenes, structural isomers of porphyrin, are reported. They are synthesized in good yields by reacting the free-base porphycene ligands with BF3·Et2O through a microwave-assisted method. Depending on the substituent group of porphycenes, two different coordination structures, mono- and diboron porphycenes, are obtained simultaneously. The single crystal structures and DFT calculations suggest that the boron atom of the monoboron porphycene is favorably coordinated on the dipyrroethene site, and the regioisomer of diboron porphycene is of cisoid stereochemistry, which is more stable than transoid. We also investigate the protonation behavior of boron porphycene complexes. Diboron porphycene does not undergo protonation, whereas monoboron porphycene undergoes protonation at the nonboron coordinating pyrroline site, resulting in a red shift in both absorption and emission spectra. Protonation and deprotonation of monoboron porphycene can be reversibly triggered using acids and bases.

A study on the aromaticity and magnetic properties of N-confused porphyrins

In this paper, topological resonance energy (TRE) methods were used to describe the global aromaticity of nitrogen confused porphyrin (NCP) isomers. The TRE results show that all NCP isomers exhibit lower aromaticity than the normal porphyrins, and their aromaticity decreases as the number of confused pyrrole rings in the molecule increases. In the NCPs, global aromaticity decreases as the distance between the nitrogen atoms increases. The bond resonance energy (BRE) and circuit resonance energy (CRE) indices were applied to study local aromaticity and conjugated pathways. Both the BRE and CRE indices revealed that individual pyrrolic subunits maintain their strong aromatic character and are the main source of global aromaticity. Ring currents (RC) were analysed using the Hückel–London model. RC results revealed that the macrocyclic electron conjugation pathway is the main source of diatropicity. As the number of confused pyrrole rings in the molecule increases, its diatropicity gradually decreases. In the confused pyrrole rings of the NCP isomers, the diatropic RC passing through the β-positions is always weaker than that passing through the inner sections. This is unrelated to the location of the protonated or non-protonated nitrogen atom at the periphery of the molecule and must be ascribed to the unique properties of the confused pyrrole rings.

Matrix isolation studies of vibrational structure of hemiporphycene

Parent, unsubstituted free base hemiporphycene, a constitutional isomer of porphyrin, was synthesized only a few years ago, and the detailed characterization of vibrational structure is lacking. We studied vibrations of hemiporphycene using site-selected fluorescence and IR measurements in low temperature argon and nitrogen matrices, combined with recording Raman spectra of polycrystalline samples. Temperature dependence of IR and Raman spectra was also investigated. The spectra were analysed with the help of DFT calculations of vibrational energies and transition intensities. Most of the bands observed in the 600-1600 cm−1 range could be reliably assigned. Moreover, it was possible to photoconvert the lowest energy trans1 tautomer, the only species present at low temperatures, into a higher energy trans2 form. However, this process is not efficient and strongly depends on the chromophore microenvironment.