Metalloporphyrins substitution

As part of the work on model heme FeNO complexes, mechanistic studies on the reversible binding of nitric oxide to metmyoglobin and water soluble Fe, Co and Fe porphyrin complexes in aqueous solution, ligand-promoted rapid NO or NO2 dissociation from Fe porphyrins, reductive nitrosylation of water-soluble iron porphyrins, activation of nitrite ions to carry out O-atom transfer by Fe porphyrins, demonstration of the role of scission of the proximal histidine-iron bond in the activation of soluble guanylyl cyclase through metalloporphyrin substitution studies, reactions of peroxynitrite with iron porphyrins, and the first observation of photoinduced nitrosyl linkage isomers of FeNO heme complexes have been reported. 

The high stability of porphyrins and metalloporphyrins is based on their aromaticity, so that porphyrins are not only most widespread in biological systems but also are found as geoporphyrins in sediments and have even been detected in interstellar space. The stability of the porphyrin ring system can be demonstrated by treatment with strong acids, which leave the macrocycle untouched. The instability of porphyrins occurs in reduction and oxidation reactions especially in the presence of light. The most common chemical reactivity of the porphyrin nucleus is electrophilic substitution which is typical for aromatic compounds. 

It was shown that dibenzothiophene oxide 17 is inert to 1-benzyl-l,4-dihydro nicotinamide (BNAH) but that, in the presence of catalytic amounts of metalloporphyrin, 17 is reduced quantitatively by BNAH. From experimental results with different catalysts [meso-tetraphenylporphinato iron(III) chloride (TPPFeCl) being the best] and a series of substituted sulfoxides, Oae and coworkers80 suggest an initial SET from BNAH to Fe1 followed by a second SET from the catalyst to the sulfoxide. The results are also consistent with an initial coordination of the substrate to Fem, thus weakening the sulfur-oxygen bond in a way reminiscent of the reduction of sulfoxides with sodium borohydride in the presence of catalytic amounts of cobalt chloride81. 

Litde is known about the stability of these porphyrins in O2 reduction, how this peripheral substitution affects O2 affinity of the metalloporphyrin, how the peripheral metal complexes perturb the energetics of various intermediates, and/or the kinetics of various steps or the mechanisms of O2 reduction by these porphyrins. At present, it remains to be seen if the strategy of coordinating metal complexes on the periphery of a metalloporphyrin can be exploited in the rational design of new ORR catalysts. 

Ligand substitution reactions of NO leading to metal-nitrosyl bond formation were first quantitatively studied for metalloporphyrins, (M(Por)), and heme proteins a few decades ago (20), and have been the subject of a recent review (20d). Despite the large volume of work, systematic mechanistic studies have been limited. As with the Rum(salen) complexes discussed above, photoexcitation of met allop or phyr in nitrosyls results in labilization of NO. In such studies, laser flash photolysis is used to labilize NO from a M(Por)(NO) precursor, and subsequent relaxation of the non-steady state system back to equilibrium (Eq. (9)) is monitored spectroscopically. 

B. Jiang, S.-W. Yang, R. Niver, and W.E. Jones, Jr., Metalloporphyrin polymers bridged with conjugated cyano-substituted stilbene units, Synth. Met., 94 205-210, 1998. 

The metalloporphyrin-initiated polymerizations are accelerated by the presence of steri-cally hindered Lewis acids [Inoue, 2000 Sugimoto and Inoue, 1999]. The Lewis acid coordinates with the oxygen of monomer to weaken the C— O bond and facilitate nucleophilic attack. The Lewis acid must be sterically hindered to prevent its reaction with the propagating center attached to the prophyrin structure. Thus, aluminm ortho-substituted phenolates such as methylaluminum bis(2,6-di-/-butyl-4-methylphenolate) accelerate the polymerization by factors of 102-103 or higher. Less sterically hindered Lewis acids, including the aluminum phenolates without ortho substituents, are much less effective. 

Much recent work has been aimed at overcoming this problem, and two approaches have been partially successful. The first is the elegant steric approach porphyrins have been substituted in a fashin that inhibits dimerization. The second approach is to attach the heme complexes to a rigid polymer chain at low concentration so as to prevent two heme complexes from approaching each other in such a manner as to lead to dimerization. By these means a reversible reaction between molecular oxygen and metalloporphyrins has been achieved. 

Porphyrins can also be sulfonated a t the peripheral positions, and copper(II) porphyrins react with thiocyanogen to give the methine-thiocyanatoporphyrin which can be hydrolyzed to the corresponding mercapto derivative. Reactions between metalloporphyrins and car- benes are known, but they tend to give mixtures of products owing to addition at methine positions as well as across peripheral double bonds. Nitrenes also react with metal-free porphyrins to give insertion products and methine-substituted derivatives. 

The most common reactions involving nucleophiles and porphyrin systems take place on the metalloporphyrin 77-cation radical (i.e. the one-electron oxidized species) rather than on the metalloporphyrin itself. One-electron oxidation can be accomplished electrochemi-cally (Section 3.07.2.4.6) or by using oxidants such as iodine, bromine, ammoniumyl salts, etc. Once formed, the 77-cation radicals (61) react with a variety of nucleophiles such as nitrite, pyridine, imidazole, cyanide, triphenylphosphine, thiocyanate, acetate, trifluoroace-tate and azide, to give the correspondingly substituted porphyrins (62) after simple acid catalyzed demetallation (79JA5953). The species produced by two-electron oxidations of metalloporphyrins (77-dications) are also potent electrophiles and react with nucleophiles to yield similar products. 

Metalloporphyrin mono- and di-anions are readily formed, most conveniently by electrochemical methods, and as would be expected they behave as strong nucleophiles. They react rapidly with proton sources or with electrophiles such as methyl iodide, and the products are usually substituted on methine carbons 5 and 15 to give derivatives such as (63), which are called porphodimethenes. 

The relative stabilities of metalloporphyrins can be compared by transmetallation reactions.18 As expected from the Zjyi ratio, monovalent metals are easily displaced by other metal ions. The order of stability is indicated as follows Cu > Zn > Cd > Hg > Pb (> Ba) > Li > Na > K. In most cases the transmetallation rate is first order both in metal ion and in metalloporphyrin, and the intermediate is considered to be the dinuclear complex [M(Por)M ] For Cu/Zn(2,4-disubstituted DPIX DME) in boiling pyridine, the substitution rate increases as the porphyrin basicity decreases, i.e. substituent = Br > CH—CH2 > CH2CH3(> Etio). 

The metal-to-porphyrin backbonding [190] increases in the series Ni(II) < Pd(II) < Pt(II) for the corresponding metalloporphyrins. It was speculated that in the same sense, due to the -donation to the porphyrin ring, electrophilic substitution might be accelerated. However, a systematic study of the relative... 

In the most important series of polymers of this type, the metallotetraphenylporphyrins, a metalloporphyrin ring bears four substituted phenylene groups X, as is shown in 7.19. The metals M in the structure are typically iron, cobalt, or nickel cations, and the substituents on the phenylene groups include -NH2, -NR2, and -OH. These polymers are generally insoluble. Some have been prepared by electro-oxidative polymerizations in the form of electroactive films on electrode surfaces.79 The cobalt-metallated polymer is of particular interest since it is an electrocatalyst for the reduction of dioxygen. Films of poly(trisbipyridine)-metal complexes also have interesting electrochemical properties, in particular electrochromism and electrical conductivity.78 The closely related polymer, poly(2-vinylpyridine), also forms metal complexes, for example with copper(II) chloride.80... 

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