Meso-carbons

The meso carbon atom should present a carbenium structure with a low TT electron density in the ground state, in the excited state this carbon possesses the carbeniate structure (C ) with a high tt electron density (119). An electron-donating group in such a position should stabilize the ground state and rise the excited state to the highest level hypsochromic shift results as a whole. 

Yamada, Y., Imamura, T., Kakiyama, H., Honda, H., Oi, S., and Fukuda, K., Characteristics of meso-carbon microbeads separated from pitch. Carbon, 1974, 12, 307 319. 

The reaction of benzyl radicals wdth several heterocyclic compounds W as more extensively studied by Waters and Watson, " - who generated benzyl radicals by decomposing di-tert-butyl peroxide in boiling toluene. The products of the reaction with acridine, 5-phenyl-acridine, 1 2- and 3 4-benzacridine, and phenazine were studied. Acridine gives a mixture of 9-benzylacridine (17%) (28) and 5,10-dibenzylacridan (18%) (29) but ho biacridan, w hereas anthracene gives a mixture of 9,10-dibenzyl-9,10-dihydroanthracene and 9,9 -dibenzyl-9,9, 10,10 -tetrahydrobianthryl. This indicates that initial addition must occur at the meso-carbon and not at the nitrogen atom. (Similar conclusions were reached on the basis of methylations discussed in Section III,C.) That this is the position of attack is further supported by the fact that the reaction of benzyl radicals with 5-... 

The conclusion that the initial attack of benzyl radicals on acridine occurs at the meso-carbon atom receives further support from the... 

This interpretation for acridine is consistent with the finding of Waters and Watson that benzyl radicals attack the meso-carbon but not nitrogen, but it is possible that methyl radicals, like benzyl radicals, also react at the nitrogen centers of phenazine (cf. Section... 

Porphyrazines (pz), or tetraazaporphyrins, are compounds that can be viewed as porphyrin variants in which the meso carbon atoms are replaced with nitrogen atoms, as Fig. 1 shows (1). This difference intrinsically gives porphyrazines discrete physiochemical properties from the porphyrins. In addition, despite their similar molecular architecture, porphyrazines are prepared by an entirely different synthetic route than porphyrins—by template cyclization of maleonitrile derivatives, as in Fig. 2, where the open circle with the A in it represents the peripheral substituent of the pz—rather than by the condensation of pyrrole and aldehyde derivatives (1). The pz synthetic route allows for the preparation of macrocycles with chemical and physical properties not readily accessible to porphyrins. In particular, procedures have been developed for the synthesis of porphyrazines with S, N, or O heteroatom peripheral functionalization of the macrocycle core (2-11). It is difficult to impossible to attach the equivalent heteroatoms to the periphery of porphyrins (12). In addition, the preparation and purification of porphyrazines that bear two different kinds of substituents is readily achievable through the directed cocyclization of two different dinitriles, Fig. 3 (4, 5, 13). 

Methyl-4-phenylcyclohexa-2,5-dienone, a molecule containing a meso carbon, shows stereoselectivity in its reaction with p-tert-butylthiophenol catalyzed by cinchonidine (eq. [17]) (63). The trans cis ratio was found to be 3 1, with the cis adduct showing an e.e. of 77% and the trans adduct an e.e. of 50%. 

The example of the thiol addition reaction to a cyclohexadienone indicates that discrimination of this type can be carried out catalytically the proximity of the meso carbon to the reaction center increases the stereoselectivity substantially. 

Levy, H. R., Talalay, P., Vennesland, B. The steric course of enzymatic reactions at meso carbon atoms application of hydrogen isotopes. In progress in stereochemistry (ed. de la Mare and Klyne), Vol. 3, p. 299—349. (London Butterworths 1962. 

However, this explanation is not sufficient to accoimt for the bipha-sic CD spectrum of human ferri-protoheme—hemopexin (with 2,4-vinyl substituents), as well as the much weaker human CO-ferro-heme-hemopexin bisignate signal compared to the rabbit congener (139), and hence other factors must be involved. Several potential effectors exist (a) exciton coupling (b) the conformers produced by a 180° rotation about the a- and y-meso-carbon axis and consequent nonisometric interactions of the as5unmetric 2,4- and 9,10-substituents (c) the aromatic tryptophan residues near the heme binding site (s) and (d) two independent binding modes or sites. 

Fig. 18. Two views of the distal helix and its relation to the heme. Each view (top and bottom) is represented as a stick model and a CPK model. Note that the distal helix approaches quite close to the heme such that backbone atoms make direct contact with the heme. The top view shows that the a-meso position is the most exposed while the remaining meso carbons are masked by the distal helix, leaving the a-meso position open for reaction. The locations of G139 and G143, which provide flexibility, are indicated.

However, in contrast to the human His25Ala HO-l heme complex, which has no detectable activity in the absence of imidazole (78), the His20Ala Hmu O rheme complex in the presence of NAD PH and NADPH-cytochrome P450 reductase was foimd to catalyze the initial meso-hydroxylation of the heme (151). The product of the reaction was Fe verdoheme, as judged by the electronic absorption spectrum and the detection of carbon monoxide as a product of the reaction. Hydrolytic conversion of the verdoheme product to biliverdin and subsequent HPLC analysis confirmed that the oxidative cleavage of the porphyrin macrocycle was specific for the a-meso-carbon. 

Such a distribution has a plausible physical basis, since the driving force for phenyl rotation into the porphyrin plane provided by the electronic excitation (the eg orbital has particularly large coefficients at the meso carbon atoms ( )) encounters steric resistance from the non-bonded interactions between the protons at the ortho positions of the phenyl groups and those on the outer pyrrole carbon atoms (20). Consequently the phenyl torsion potential in the excited states may be relatively flat. Nevertheless, the vibrational frequencies are expected to be sensitive to the torsion angle for orientation close to co-planar because of the effect of conjugation. 

It must be concluded, however, that the stages of biosynthesis at which ring contraction and the loss of the C-12 acetate carboxyl occur are still unknown. It is open to conjecture whether introduction of the remaining five methionine derived methyl groups occurs at the isobacteriochlorin level or after extrusion of the C-20 meso- carbon. It has been shown that the CD3 groups of [CD3]methionine are transferred to all seven methylated positions without loss of deuterium. 

H-5), 7.5-6.8 (unsaturated JS-H), 2.0 (NH) for (iBchl).2,14 The signal of a proton on the meso carbon attached to a pyrroline ring is located at 1 p.p.m. higher frequency than the others partly because of the increased electron density on the position and partly because of the loss of pyrrolic ring current effects. 

Corroles are stronger acids and weaker bases than porphyrins.239 They are deprotonated in dilute alkali to form aromatic anions. In acidic media, the first protonation occurs on the pyrrole nitrogen, but the second proton adds to the meso carbon causing loss of the aromaticity (Scheme 72). 

---