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.

6-Azahemiporphycene: a new member of the porphyrinoid family.

The reaction of 5,10,15-triarylcorrole with 4-amino-4H-1,2,4-triazole provides another example of corrole ring expansion to give the corresponding 6-azahemiporphycene, a novel porphyrin analogue. The facile oxidation of the corrole ring is a required step for the ring expansion and for this reason the reaction fails in the case of corroles bearing meso-phenyl groups carrying electron-withdrawing substituents. Steric requirements also limited the scope of the reaction, which is not successful in the case of 2,6-disubstituted meso-aryl corroles. The occurrence of an initial oxidation is further supported by formation of the 6-azahemiporphycene derivative when the reaction is carried out under the same conditions, using a 5- or a 10-isocorrole as starting material. (1)H NMR spectra and X-ray crystal characterization of 6-azahemiporphycene evidenced the presence of an intramolecular N-H...N hydrogen bond in the inner core of the macrocycle, while photophysical characterization confirmed the aromatic character of the novel macrocycle, showing an intense Soret-like band around 410 nm in the absorption spectrum. The fluorescence emission is very modest, and 6-azahemiporphycene showed higher photostability than the corresponding corrole species. Different metal complexes of 6-azahemiporphycene were prepared following synthetic protocols usually exploited for the preparation of metalloporphyrins, demonstrating good coordination properties for the macrocycle. Both the free-base and metal derivatives were characterized by cyclic voltammetry and spectroelectrochemistry in dichloromethane and benzonitrile. To further detail the behavior of this novel macrocycle, density functional theory (DFT) calculations were carried out on the basic structure of 6-azahemiporphycene with the aim of assessing aromaticity and tautomerism, as well as calculating its stability with respect to the 5-aza isomer.

A prospective blinded evaluation of urinary porphyrins verses the clinical severity of autism spectrum disorders.

A prospective, blinded study evaluated the relationship between autism spectrum disorder (ASD) severity measured by Childhood Autism Rating Scale (CARS) scores and urinary porphyrins among a cohort of participants (n = 26). LabCorp (CLIA-approved) tested for uroporphyrins, heptacarboxylporphyrins, hexacarboxylporphyrins, pentacarboxylporphyrins, coproporphyrin (cP) I, and cP III levels. Participants with severe ASD had significantly increased cP I, cP III, and total cP levels in comparison to participants with mild ASD. A significant correlation was observed between increasing cP levels and CARS scores. Significant correlations were also noted for comparative urinary porphyrin testing between LabCorp and the Laboratoire Philippe Auguste (ISO-approved) for total cP. Finally, total cP measured at LabCorp was found to significantly correlate with precoproporphryin (a specific porphyrin marker for mercury toxicity) measured at the Laboratoire Philippe Auguste. Since urinary porphyrin testing is clinically available, relatively inexpensive, and noninvasive, it may be used to help suggest whether heavy metal toxicity is associated with ASD.

Urinary arsenic speciation and porphyrins in C57Bl/6J mice chronically exposed to low doses of sodium arsenate.

Arsenic has been classified as a human carcinogen based on epidemiological data however the mechanism of its carcinogenicity is still unclear. Urinary biomarkers for chronic arsenic exposure would be valuable as an early warning indicator for timely interventions. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500 microg Asv/L as sodium arsenate ad libitum for 12 months. Urine was collected bimonthly for urinary arsenic methylation assay and porphyrin analysis. All detectable arsenic species showed strong linear correlation with administered dosage and the arsenic methylation patterns were similar in all three treatment groups. No significant changes of methylation patterns were observed over time for either the control or test groups. Urinary coproporphyrin III was significantly increased in the 8th month in 250 and 500 microg/L groups and remained significantly dose-related after 10 and 12 months. Coproporphyrin I also showed a significant dose-response relationship after 12 months. Our results confirm that urinary arsenic is a useful biomarker for internal dose. The alteration of porphyrin profile suggests that arsenic can affect the heme metabolism and this may occur prior to the onset of arsenic induced carcinogenesis.

Mass spectral study of meso-alkyl and meso-cycloalkyl calix(4)pyrroles under electron impact conditions.

A series of meso-cycloalkyl calix(4)pyrroles (I) and meso-dialkyl calix(4)pyrroles (II) has been studied under electron ionization (EI) mass spectral conditions. All the calix(4)pyrroles showed prominent molecular ions. The cleavage of the C--C bond linked at position 2 of the pyrrole ring (beta-cleavage) is the foremost and dominant fragmentation process. The beta-cleavage process, either through ring opening or directly, results in the loss of an alkyl radical from the molecular ion. The collision-induced dissociation (CID) spectra of I showed specific sequential expulsion of pyrrole and/or cycloalkyl rings from the molecular ion with or without hydrogen migrations, revealing more information on the structure of individual compounds than was available from the EI spectra. The isomeric cycloalkyl calix(4)pyrroles showed distinguishable CID spectra, indicating structure specificity in initial ring opening whereas, in the case of II, the EI mass spectrum contains all the structure-indicative fragment ions. The CID spectra of II resulted in a dominant [M-R]+ ion, with other characteristic ions being less abundant.

Identification of monovinyl tripropionic acid porphyrins and metabolites from faeces of patients with hereditary coproporphyria by high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

Harderoporphyrin (2-vinyl-4,6,7-tripropionic acid porphyrin) and its metabolites in faeces of patients with hereditary coproporphyria (HCP) have been separated and characterized by high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC/ESI-Q-TOFMS/MS). The metabolites identified were 2-ethyl-4,6,7-tripropionic acid porphyrin, 2-hydro-4,6,7-tripropionic acid porphyrin, 2-methoxyethyl-4,6,7-tripropionic acid porphyrin and 2-acetyl-4,6,7-tripropionic acid porphyrin. Isomers of harderoporphyrin derived from isomerization of harderoporphyrinogen were also detected.

A comparative study of manganese meso-sulfonatophenyl porphyrins: contrast-enhancing agents for tumors.

Four manganese meso-sulfonatophenyl porphyrins were prepared, characterized and investigated for their potential as tumor-specific MRI contrast-enhancing agents in mice bearing subcutaneous implants of a mammary carcinoma (SMT-F). The trisulfonated tetraphenyl porphyrin, MnTPPS3 presented the most favorable profile: bio-distribution, tumor concentration and tumor relaxivity, when compared at 24 hr postinjection. Imaging experiments revealed that a time-dependent delineation of tumor morphology occurs in response to MnTPPS3 that appears to correlate with necrotic regions of the tumor.

New developments in the regulation of heme metabolism and their implications.

Various endogenous and exogenous chemicals, such as hormones, drugs, and carcinogens and other environmental pollutants are enzymatically converted to polar metabolites as a result of their oxidative metabolism by the mixed-function oxidase system. This enzyme complex constitutes the major detoxifying system of man and utilizes the hemoprotein--cytochrome P-450--as the terminal oxidase. Recent studies with trace metals have revealed the potent ability of these elements to alter the synthesis and to enhance the degradation of heme moiety of cytochrome P-450. An important consequence of these metal actions is to greatly impair the ability of cells to oxidatively metabolize chemicals because of the heme dependence of this metabolic process. In this report the effects of exposure to trace metals on drug oxidations is reviewed within the framework of metal alterations of heme metabolism, including both its synthesis and degradation, since these newly discovered properties of metals have made it possible to define a major dimension of metal toxicity in terms of a unified cellular mechanism of action.