Porphyrins iron-57 insertion

Iron Insertion into Free-base Porphyrins... 

Condensatfon of 57 with trans-urocanic acid chloride (62) furnished the chelated porphyrin In this case the imidazole was attached at the C-4 rather than the more common N-1 position to allow deprotonation to the imidazolate. After iron insertion and deprotonation addition of Cu(acac)2 yielded the p-imidazolato binuclear complex 64 (Scheme 24), a potential model for the [Cu5 /Cyta ] center of cytochrome oxidase. 

Since the S-protected pentanoic acid derivatives were more difficult to obtain, the bromoalkyl chain was first attached to the porphyrin to give 85 and the thio group introduced by treatment with either TrS K or AcS K. Deacetylation (MeOH/NHj) or detritylation (Hg /H2S) gave the free thiol. However, after iron insertion, visible spectra indicated that the alkyl chain was too flexible to hold the mercaptan at the metal site the spectra, in toluene, were similar to those of square planar four-coordinate iron(II) species. The introduction of CO does lead to the formation of sw-coordinate low-spin Fe"-CO complexes. 

Scheme The mixed metal compound with iron inserted into the porphyrin... 

Momenteau s route to doubly-strapped porphyrins was easily adapted to produce compounds in which an axial base was incorporated into one of the straps Condensation of tetra(o-hydroxyphenyl)porphyrin (250) (mbcture of four isomers) with one equivalent of 1,12-dibromododecane gave a mixture of two singly-linked porphyrins, depending on whether adjacent (255), or opposite (254) meso-phenyl groups were linked. This mixture was reacted with 3,5-bis(3-bromopropyl)pyridine 256 and the desired cross trans-linked isomer 257 isolated by preparative tic (5% overall yield) (Scheme 77). A similar porphyrin 259 was prepared from a,p,a,p-tetra(o-aminophenyl)porphyrin (142) in this case the straps were tied to the porphyrin skeleton by amide linkages (Scheme 78). Following iron insertion and reduction, visible absorption and H-NMR spectra of both compounds were consistent with a five-coordinate high spin (S = 2) iron(II) complex. 

Next, we discuss insertion of iron to synthesize binuclear high-spin iron(III) (5 = )-molybdenum compounds. Iron insertion into the porphyrin core is more complicated and requires strict exclusion of HCl from the reaction mixture and product complexes to avoid the acid hydrolysis of the catecholato ligand from the molybdenyl group. The p-oxo dimer generated during purification is cleaved by aqueous NaCl in a biphasic reaction. 

Attempts to isolate an iron-inserting enzyme are hampered by the relative ease of nonenzymic iron incorporation into porphyrins under appropriate conditions. Extracts of erythrocytes (148-161) or of mitochondria (168) are found to form heme from ferrous iron and PROTO. However if PROTO is solubilized, i.e., not colloidal and if ferrous iron is kept reduced and is not tightly tied up by buffers, amines, etc., then heme formation readily occurs in the absence of any enzyme. Possibly kinetics and specificity tests will help to isolate the enzymic process. Some steps along these lines have been reported (163). 

Reaction of free-base porphyrin compounds with iton(II) salts in an appropriate solvent results in loss of the two N—H protons and insertion of iron into the tetradentate porphyrin dianion ligand. Five-coordinate iton(III) porphyrin complexes (hemins), which usually have the anion of the iton(II) salt for the fifth or axial ligand, ate isolated if the reaction is carried out in the presence of air. Iron(II) porphyrin complexes (hemes) can be isolated if the reaction and workup is conducted under rigorously anaerobic conditions. Typically, however, iton(II) complexes are obtained from iton(III) porphyrin complexes by reduction with dithionite, thiolate, borohydtide, chromous ion, or other reducing agents. 

One-electron oxidation of the vinylidene complex transforms it from an Fe=C axially symmetric Fe(ll) carbene to an Fe(lll) complex where the vinylidene carbon bridges between iron and a pyrrole nitrogen. Cobalt and nickel porphyrin carbene complexes adopt this latter structure, with the carbene fragment formally inserted into the metal-nitrogen bond. The difference between the two types of metalloporphyrin carbene, and the conversion of one type to the other by oxidation in the case of iron, has been considered in a theoretical study. The comparison is especially interesting for the iron(ll) and cobalt(lll) carbene complexes Fe(Por)CR2 and Co(Por)(CR2) which both contain metal centers yet adopt... 

Iron porphyrins containing vinyl ligands have also been prepared by hydromet-allation of alkynes with Fe(TPP)CI and NaBH4 in toluene/methanol. Reactions with hex-2-yne and hex-3-yne are shown in Scheme 4. with the former giving two isomers. Insertion of an alkyne into an Fe(III) hydride intermediate, Fe(TPP)H, formed from Fe(TPP)Cl with NaBH4, has been proposed for these reactions. " In superficially similar chemistry, Fe(TPP)CI (present in 10 mol%) catalyzes the reduction of alkenes and alkynes with 200 mol% NaBH4 in anaerobic benzene/ethanol. For example, styrene is reduced to 2,3-diphenylbutane and ethylbenzene. Addition of a radical trap decreases the yield of the coupled product, 2,3-diphenylbutane. Both Fe(lll) and Fe(II) alkyls, Fe(TPP)CH(Me)Ph and [Fe(TPP)CH(Me)Ph] , were propo.sed as intermediates, but were not observed directly. ... 

Alkyliron(lll) porphyrin complexes are air. sensitive, and when exposed to oxygen under ambient conditions the products are the very stable iron(IIl) /t-oxo dimers, [Fe(Por)]20. A more careful investigation revealed that the reaction of the alkyl complexes with oxygen proceeds via insertion of O2 into the Fe—C bond. " When a solution of Fe(Por)R (R = Me, Et, i-Pr) is exposed to O2 at —70 C, the characteristic H NMR spectrum of the low spin iron alkyl complex disappears and is replaced by a new, high spin species. The same species can be generated from the reaction of an alkyl hydroperoxide with Fe(Por)OH, and is formulated as... 

Iron(II) alkyl anions fFe(Por)R (R = Me, t-Bu) do not insert CO directly, but do upon one-electron oxidation to Fe(Por)R to give the acyl species Fe(Por)C(0)R, which can in turn be reduced to the iron(II) acyl Fe(Por)C(0)R]. This process competes with homolysis of Fe(Por)R, and the resulting iron(II) porphyrin is stabilized by formation of the carbonyl complex Fe(Por)(CO). Benzyl and phenyl iron(III) complexes do not insert CO, with the former undergoing decomposition and the latter forming a six-coordinate adduct, [Fe(Por)(Ph)(CO) upon reduction to iron(ll). The failure of Fe(Por)Ph to insert CO was attributed to the stronger Fe—C bond in the aryl complexes. The electrochemistry of the iron(lll) acyl complexes Fe(Por)C(0)R was investigated as part of this study, and showed two reversible reductions (to Fe(ll) and Fe(l) acyl complexes, formally) and one irreversible oxidation process."" ... 

Up to this point, the biosynthesis steps are identical for both chlorophyll and haem, bnt depending on which metal is inserted in the center of the porphyrin, the pathway branches to form one or another. The insertion of iron is followed by... 

Unusual iron-porphyrin vinylidene complexes were obtained from DDT [l,l-bis(4-chlorophenyl)-2,2,2-tricMoroethane] and Fe(tpp) [tpp = meso-tetraphenylporphinato (2-)] in the presence ofa reducing agent [10a, 264]. The derived N,N -vinylene-bridged porphyrin reacts with metal carbonyls [Fe3(CO)i2, Ru3(CO)i2] to break one or both N—C bonds with insertion of the vinylidene into an M—N bond. While the iron complex was formed in 90% yield, the reaction with Ru3(CO)i2 afforded three products, the vinylidene being formed in only 40% yield [265]. 

Insertion of metals into the porphyrin and chlorin ring occurs with variable ease (and difficulty) commonly employed metals such as zinc(II), copper(II) and nickel(II) are simply chelated using the corresponding metal acetate in methanol, but others such as mag-nesium(II) and iron(III) require specialized conditions. Since a full description of the best method for any particular case is outside the scope of this Chapter, readers are advised to consult recent reviews (B-75MI30703, B-75MI30704). 

Iron is usually inserted into porphyrins by heating them with an Fe" salt in a solvent.14,17 The systems most commonly used are FeCl2/DMF, FeS04/py-AcOH, Fe(OAc)2/HOAc and FeBr2/ base/C6H6-THF. Fe(acac)2 may also serve as a metal carrier. Fe(CO)s is used to metallate sterically hindered porphyrins.62... 

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