Allomerization of bacteriochlorophyll a (Bchl a) was studied under various reaction conditions. Bchl a on stirring with KOH/propanol produced an "unstable bacteriochlorin", which decomposed in acidic conditions to give a complex mixture containing bacteriopurpurin a as a principal component. The yields of other compounds varied and were found to be dependent on reaction condition. The structures of the isolated porphyrins, chlorins, and bacteriochlorins, related to Bchl a, were assigned on the basis of 1D, 2D NMR (ROESY), and mass spectroscopy analyses. The presence of fused anhydride rings in porphyrin, chlorin, and bacterichlorin systems showed a significant influence on their optical properties. Compared to bacteriochlorophyll a and bacteriopheophytin, the related structurally modified analogues, e.g., the bacteriopurpurin a, 13(1)/15(1)-N-alkyl isoimide, and the imide analogues were found to be more stable with a significant difference in spectroscopic properties. Bacteriochlorins containing anhydride, imide, or isoimide cyclic rings demonstrated a significant bathochromic shift of their Q bands in their electronic absorption spectra. Under basic conditions the formation of the 12-hydroxymethyl, 12-formyl, and 12-methylene analogues as byproducts from the 12-methyl-bacteriopurpurin-N-hexylimide could be due to subsequent oxidation of the vinylogous enolate intermediates. To investigate the effect of the central metal in the electronic spectra, the stable bacteriopurpurin-18-N-hexylimide was converted to a series of metal complexes [Zn(II), Cd(II), and Pd(II)] by following the direct or transmetalation approaches. Compared to the free-base analogue, these complexes showed a remarkable shift in their electronic absorption spectra.

Diazomethane reacts regioselectively with peripheral vinyl substituents of pyropheophorbide a and purpurin-18 N-methylimide to produce corresponding 1′-pyrazolinyl-substituted derivatives as a main product. Similarly, treatment of protoporphyrin IX gave a mixture of mono- and di-substituted pyrazolinyl analogs, which were isolated as individual products. Thermolytic decomposition of the pyrazolinyl derivatives produced cyclopropyl-substituted chlorins and porphyrins. 1,3-Dipolar cycloaddition mechanisms of the formation of 1′-pyrazolinyl derivatives are discussed.

Condensation of 132-oxopyropheophorbide a 1 with various aromatic diamines under acid-catalyzed conditions afforded a series of novel chlorins with fused quinoxaline or benzimidazole polyaromatic ring systems. This methodology was extended for the preparation of laterally bridged pyropheophorbide a dimers. Reaction of 1 with 1,2,4,5-benzenetetramine produced a bis-quinoxaline-bridged symmetrical chlorin dimer 16 and an unsymmetrical benzimidazole/pyrazine bridged analog 17. Spectroscopic data of novel conjugated dimers show a significant perturbation of the extended bis-chlorin π-system in a coplanar arrangement. The excited state properties of some novel chlorin derivatives 4–6, 14, and dimers 16 and 17, which contain two laterally bridged pheophorbides have been examined. Compounds 4–6, 16 and 17 are weakly fluorescent (φf=0.08–0.16) with singlet state lifetimes ranging from 2–5ns. These compounds show high intersystem crossing efficiencies (φT=0.39–0.58). A close match was observed between the quantum yields for singlet oxygen generated and their triplet quantum yields. The excited state of 14 undergoes deactivation mainly through a non-radiative route with fluorescence and triplet state quantum yields being negligible.The monomeric and dimeric structures of annulated chlorins show a characteristic vinylogous-type enolization of the 12-methyl group adjacent to the fused ring systems. The crystallographic and the modeling studies of these novel chlorins indicated a rigid construction of condensed aromatic heterocycles in a planar arrangement.

[formula: see text] A novel approach for the preparation of symmetrical (chlorin-chlorin), and unsymmetrical (chlorin-porphyrin) dimers joined with carbon-carbon linkages as models to study the "intramolecular" charge transfer is discussed.

A novel approach for porphyrin modification is provided by ring-enlargement reactions. Treatment of dioxochlorins (see scheme) and tetraoxobacteriochlorins with diazomethane results in formation of the corresponding mono- and di(oxopyri)porphyrins.

Condensation of 132-oxopyropheophorbide a with benzene-1,2,4,5-tetramine produced a bis-quinoxaline-bridged symmetrical chlorin dimer and an unsymmetrical benzimidazole/pyrazine bridged analog. Spectroscopic data of the novel conjugated dimers show a significant perturbation of the extended bis-chlorin π-system in a coplanar arrangement.

Reaction of 13(2)-oxopyropheophorbide a with CH2N2 produced three isomeric methoxyverdinochlorins via expansion of the cyclopentanedione ring E; these long-wavelength absorbing verdinochlorins represent the first example of verdins with a reduced pyrrolic ring system, and their structural assignments have been made on the basis of H-1 NMR studies; a mechanism of verdinochlorin formation is discussed.

Treatment of pyropheophorbide a with aqueous LiOH–THF gave the corresponding enolate, which on in situ oxidation produced the corresponding 132-oxo derivative in 79% yield; prolonged autoxidation gave purpurin-18 and purpurin-5 as major products and a mechanism for the formation of 12-formyl derivative from 132-oxopyropheophorbide a under unusual enolization is discussed; the electronic absorption spectroscopy data of the enolic intermediates showed a considerable perturbation in the π-systems of the macrocycle.

The synthesis, photophysical characteristics, in viva photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phototoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-alpha, have long-wavelength absorptions in the range lambda(max) = 734-758 nm. Preferential migration of ethyl over methyl substituents among ketobacteriochlorins obtained in the pinacol-pinacolone rearrangements of vic-dihydroxybacteriochlorins was confirmed by NOE studies. The bacteriochlorins show relatively law fluorescence quantum yields. Among all the bacteriochlorins the triplet states were quenched by ground state molecular oxygen in a relatively similar manner, yielding comparable singlet oxygen quantum yields. In preliminary in viva studies (DBA/2 mice, transplanted with SMT/F tumors), ketobacteriochlorins were found to be more photodynamically active than the related vic-dihydroxy analogues. Replacement of the methyl ester functionalities with di-tert-butylaspartic acids enhanced the in vivo efficacy. Site specific human serum albumin (BSA) binding studies indicated a direct correlation between the ability of the compound to bind to the diazepam binding site (albumin site II) and the in viva photosensitizing efficacy.

A new class of stable bacteriochlorins, namely benzobacteriopurpurin bearing two exo-cyclic rings was synthesized by way of Diels-Alder cycloaddition of 8-vinyl-mesopurpurin-18 methyl ester with tetracyanoethylene (TCNE) and dimethyl acetylenedicarboxylate (DMAD). These novel bacteriochlorins have long wavelength absorptions in the range of 760 to 795 nm.

Efficient syntheses and mechanisms of the formation of some some novel porphyrins and chlorins with cyclic anhydride, imide and isoimide rings bearing various N-substituents as possible target-specific photosensitizers for photodynamic therapy are presented. Porphyrins with such cyclic ring systems are named as ''emeraldins'' due to their intense green color. This class of compounds show a unique reverse etio- type absorption spectra. (C) 1997 Published by Elsevier Science Ltd.

Syntheses and spectroscopic properties of pyropheophorbide-porphyrin dimers and a bis-pyropheophorbide-porphyrin trimer are described. Fluorescence spectroscopic data of the oligomers reveal that the macrocycles in the systems are only weakly coupled. © 1997 Elsevier Science Ltd.

New methods for conversion of unstable bacteriochlorophyll-a present in Rb. sphaeroides into stable bacteriochlorins are presented. Cyclic imide derivatives from related cyclic isoimide or amide analogs are obtained by intramolecular base catalyzed cyclization. Most of the new bacteriochlorins have long wavelength absorptions in the range of 796–822 nm. In preliminary screening, the isoimide analogs have shown promising in vivo photosensitizing activity for the treament of cancer by photodynamic therapy.

A first regioselective synthesis of bacteriochlorin by hydroxylation of metallated chlorin with OsO4 is discussed. This is the first example for the preparation of metallobacteriochlorin. This methodology can also be used for the preparation of unsymmetrical isobacteriochlorins by introducing electron-withdawing substituent(s) at the adjacent position(s) of the reduced ring. The Zn(II) vic-dihydroxybacteriochlorin obtained from 2-formyl-purpurin methyl ester showed long wavelength absorption at 828 nm which seems to be associated with electronic interactions of the substituents with the π-system of the macrocycle.

Syntheses and comparative in vivo photosensitizing efficacy of a series of chlorophyll-a derivatives with (1-heptyloxyethyl) substituents at various positions are discussed. Compared with Photofrin®, the n-heptyl ether analogues showed better in vivo sensitizing activity (DBA/2 mice transplanted with SMT/F tumors) as well as reduced skin phototoxicity. The Vilsmeier formylation of copper(II) methyl mesopyropheophorbide-a 11 did not produce the expected meso-formyl derivative 12, but instead gave the α,β-unsaturated chloroformyl analogue 13 as the major product.