Heme induces hemeoglobin synthesis Porphyrias general mechanism: ..
ABSTRACT: A mesoinic pyridylideneamide ligand (PYA) was synthetized and fully characterized and coordinated to an iridium(III) center. This ligand represents the first example of a mesoionic N-donor ligand. Structural and spectroscopic analysis revealed unique properties which were exploited in chemically driven water oxidation catalysis.
Pathophysiology of Heme Synthesis ..
Porphyrin synthesis under solvent-free conditions represents the “greening” of a traditional synthesis that normally requires large amounts of organic solvent, and has hindered industrial-scale synthesis of this useful class of molecules. We have found that the four-fold acid-catalysed condensation of aldehyde and pyrrole to yield a tetra-substituted porphyrin is possible through mechanochemical techniques, without a solvent present. This represents one of the still-rare examples of carbon-carbon bond formation by mechanochemistry. Specifically, upon grinding equimolar amounts of pyrrole and benzaldehyde in presence of an acid catalyst, cyclization takes place to give reduced porphyrin precursors (reversible), which upon oxidation form tetraphenylporphyrin (TPP). The approach has been found suitable for synthesis of a variety of meso-tetrasubstituted porphyrins. Oxidation can occur either by using an oxidizing agent in solution, to give yields comparable to those published for traditional methods of porphyrin synthesis, or through mechanochemical means resulting in a two-step mechanochemical synthesis to give slightly lower yields that are still being optimized. We are also working on “green” methods of porphyrin isolation, including entrainment sublimation, which would hopefully further reduce the need for large amounts of organic solvent. These results hold promise for the development of mechanochemical synthetic protocols for porphyrins and related classes of compounds.
Inspired by the tautomeric relationship of imidazole and N-heterocyclic carbenes, we have been intrigued about the implications of such carbenes in metalloenzymes. Enzymes are the machinery of all biological transformations, and provide inspiration for designing artificial catalysts. New insights into the mode of action of enzymes is therefore instrumental for developing more competent synthetic catalysts as well as for better understanding natural systems. In collaboration with F. Paradisi (U Nottingham), we have begun to explore carbene binding to metalloenzymes. We have been focusing on blue copper proteins such as azurin and specific mutants of azurin to investigate the possibility of carbene bonding to the copper center, and to evaluate the effect that such bonding entails. While azurin is predominantly involved in electron transfer processes through reversible copper(II) reduction and oxidation, other blue copper proteins are catalytically active in redox transformations of substrates. Hence, these enzymes provide an attractive probe to explore the relevance of carbene bonding on the catalytic performance of the enzyme.
defines the regiochemistry of porphyrin substitution is ..
INTRODUCTION: Design and synthesis of porphyrins with array of oligomers or metals substituted analogs having well-defined shapes and sizes are currently of great interesting topics to modify the photophysical properties, absorption cross-section, catalytic reactions and energy transfer reactions 1-3. In recent years, peripheral substitution, mostly at meso-positions, of platinum group metal ions has been employed in synthesizing dimeric and oligomeric type porphyrins that undergo interesting intramolecular photo processes between the porphyrin sub-units 4-7. Most examples deal with porphyrins bearing meso-pyridyl groups, since the wide coordination possibility of pyridine group allows large assemblies to be built 8.
Chem400_LabW05 | Porphyrin | Coordination Complex
Since the cyclocondensation reaction between an aldehyde and pyrrole is reversible, it was hypothesized that letting the ground pink solid stand for several days while undergoing oxidation in air was allowing the cyclized product to revert to starting material before being oxidized to the porphyrin, resulting in low yields. Therefore, in order to evaluate the success of the mechanochemical cyclocondensation reaction, the pink solid was oxidized immediately by stirring for two hours in chloroform with DDQ, followed by column chromatography to isolate the porphyrin and determine the yield. Also, in order to have better control of the mechanochemical reaction conditions, the process was automated using a Retsch MM200 mixer mill. Coupled with these modifications, the scope of the synthesis was expanded to include a series of substituted benzaldehydes. Yields from these reactions are reported in . Addition of auxiliary grinding agents during the milling process such as magnesium sulfate (to remove water), silica or sodium chloride (to alleviate “stickyness”) did not lead to an increase in yield.
Laboratory methods in porphyrin and metallo-porphyrins ..
The results show that mechanochemical condensation between an aldehyde and pyrrole to give reduced porphyrin precursors is successful for several aromatic aldehydes, producing yields similar to those reported for solution synthesis. We have also observed Soret bands resulting from reactions of several alkyl adehydes, namely butanal, pentanal, octanal, and trimethyl acetaldehyde. Characterization and determination of yield for these presumable meso-alkylsubstituted porphyrin products is ongoing, although preliminary yields are in the 10-20% range.