Dihydroporphyrin synthesis: New methodology

Selective formation of trans-nitrochlorins 16-19, cyclopropylchlorins 14, 15, and 20-23, or functionalized trans-chlorins 5-13 by reaction of 2- nitro-5,10,15,20-tetraphenylporphyrin 1 with \u27active\u27 methylene compounds such as malonates or malononitrile in the presence of base has been achieved. Reaction control is accomplished via sequential Michael additions, followed by intra-molecular nucleophilic displacement of a secondary nitro group. Steric as well as thermodynamic effects have been found to govern the selectivity of product formation. Ambient temperature or bulky carbanion substituents lead to nitrochlorins and/or cyclopropylchlorins. Increased reaction temperatures, combined with sterically less encumbered carbanion substituents, favor the formation of disubstituted trans-chlorins. Nucleophilic ring-opening reactions of cyclopropyl-derivative 14 afford disubstituted trans-chlorin products 5 and 25 and provide additional mechanistic evidence for the intermediacy of the cyclopropylchlorin. Use of porphyrins with modified meso-phenyl positions illustrates the generality of this methodology and allows a novel method for the preparation of a wide range of reduced porphyrins, which may find application in fields such as the photodynamic therapy (PDT) of cancer

Regioselective syntheses and structural characterizations of 2,3-dibromo- and 2,3,7,8,12,13-hexabromo-5,10,15,20- tetraphenylporphyrins

The title dibromoporphyrins 4/5 and hexabromoporphyrins 11/12 are prepared from H2(2NO2TPP) 1 and Cu(2-NO2TPP) 8, respectively. The β-nitro group confines the 18-π-annulene system of a tetraphenylporphyrin to its N22H-N24H aromatic delocalization pathway which induces the localization of an antipodal double bond on the porphyrin periphery and enhances its susceptibility to electrophilic attack. Dibromination of H2(2- NO2TPP) 1 occurs regioselectively affording the 12,13-dibromo-2- nitroporphyrin 2 which, upon Michael addition of NaBH4 and re- aromatization of the resulting nitrochlorin 3, provides an entry to 2,3-dibromoTPP 4/5 as well as an improved route to 2,3- dicyanoporphyrins 6/7. Perbromination of Cu(2-NO2TPP) 8 and denitration of 9 gave, after demetalation, 2,3,7,8,12,13- hexabromoTPP 12. Both 4 and 12 are structurally characterized by X-ray crystallography

Dodecasubstituted metallochlorins (metallodihydroporphyrins)

Regioseleclive bromination of 2-nitro-5,10,15,20-tetra-phenylporphyrin, cyclopropa[b]chlorins, or trans-bis-(dicyanomethyl)chlorms occurs in the pyrrole subunit opposite the substituted ring; exhaustive bromination of functionalized tetraphenylchlorins provides a route to dode-casubstitued dihydroporphyrins for the first time

Functionalization of 2,3-disubstituted-2,3-dihydro-5,10,15,20- tetraphenylporphyrins

A reduced pyrrole subunit directs electrophilic functionalizations of dihydroporphyrins to the antipodal pyrrole ring by confining the chromophore 18-π-electron delocalization pathway to its N(22)H-N(24)H tautomer. The 2,3- disubstituents inhibit oxidation, this being exemplified by the synthesis of perbrominated dodecasubstituted metallochlorins. Regiospecific nitration (using N2O4) of metal-free chlorins provides access to Michael acceptors such as 12-nitro-2,3-disubstituted chlorins which are used in the preparation of highly functionalized tetraaryl-bacteriochlorins by conjugate addition of carbon-centered nucleophiles. (C) 2000 Elsevier Science Ltd

NMR studies of nonplanar porphyrins. Part 2. Effect of nonplanar conformational distortions on the porphyrin ring current

The ring currents in the sterically congested and highly nonplanar porphyrin complexes 1a and 2a have been investigated using a double-dipole model of the porphyrin ring current effect. The equivalent dipoles needed to simulate the ring current in the saddle-shaped complex 1a were indistinguishable from those previously determined for the planar or nearly planar complex 3a. A 5% decrease in the equivalent dipoles was required to reproduce the ring current shifts in the ruffled complex 2a. The extremely large nonplanar conformational distortions seen for the porphyrin macrocycles in complexes 1a and 2a thus seem to cause little decrease in the porphyrin ring currents measured by this empirical model

NMR studies of nonplanar porphyrins. Part 1. Axial ligand orientations in highly nonplanar porphyrins

The ligand orientations in the nonplanar porphyrin complexes 1a-e and 2a-e have been investigated using molecular mechanics calculations and proton NMR spectroscopy. The minimum energy structures calculated for complexes 1a-e show that the planes of the axial pyridine or imidazole ligands are orientated approximately parallel to the CoIII-Nporphyrin bonds, with the ligand ring planes being perpendicular to each other. For complexes 2a-e, the planes of the axial ligands in the calculated minimum energy structures are orientated along the porphyrin meso carbon axis and the ligand ring planes are perpendicular to each other. Thus, for both series of complexes the planes of the axial ligands are orientated parallel to cavities formed by these very nonplanar porphyrins. Proton NMR studies suggest that structures similar to those obtained from the molecular mechanics calculations are retained in solution. In some complexes, hindered rotation of the axial ligands is also observed. Complexes 1a-e and 2a-e are unusual examples of the porphyrin conformation influencing the orientations of axial ligands and, as such, may be useful as models for studying ligand orientation effects in relation to biological systems

Iturbide Palace

The applicability of matrix-assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry to the analysis of porphyrins has been examined. High resolution spectra were readily obtained with good sensitivity and a detection limit as low as 2 fmol. A mixed solvent system of toluene and ethanol (1:1 by volume) proved to be compatible with the 2,5-dihydroxybenzoic acid (DHB) matrix and solubilized most of the porphyrins examined in this study. Porphyrins which were insoluble in this solvent mixture could be dissolved in an appropriate solvent and deposited on a layer of DHB (layered MALDI). The parent ion was generally the largest peak in the spectrum, although for some metalloporphyrins the peak corresponding to (M - metal + 3H)+ was dominant. The extent of demetallation was found to depend on factors such as sample preparation, the metal ion and the laser intensity. Addition of more than one hydrogen occurred in many cases but was a minor process. Spectra of compounds ionized by different methods showed increasing fragmentation in the order MALD