Highly Selective Synthesis of the Ring-B Reduced Chlorins by Ferric Chloride-Mediated Oxidation of Bacteriochlorins: Effects of the Fused Imide vs Isocyclic Ring on Photophysical and Electrochemical Properties

Abstract

The oxidation of bacteriopyropheophorbide with ferric chloride hexahydrate or its anhydrous form produced the ring-D oxidized (ring-B reduced) chlorin in >95% yield. Replacing the five-member isocyclic ring in bacteriopyropheophorbide- a with a fused six-member N-butylimide ring system made no difference in regioselective oxidation, and the corresponding ring-B reduced chlorin was isolated in almost quantitative yield. When the oxidant was replaced by 2,3-dichloro-5,6-dicyano-p-benzoquinone, which is frequently used at the oxidizing stage of the porphyrin synthesis, the ring-B oxidized (ring-D reduced) chlorins were obtained. With both ring-B reduced and ring-D reduced chlorins in hand, their photophysical and electrochemical properties were examined and compared for the first time. The ring-B reduced chlorine 20, with a fused six-member N-butylimide ring, exhibits the most red-shifted absorption band (at lambda(max) = 746 nm), the lowest fluorescence quantum yield (4.5%), and the largest quantum yield of singlet oxygen formation (67%) among the reduced ring-B and ring-D chlorins investigated in this study. Measurements of the one-electron oxidation and reduction potentials show that compound 20 is also the easiest to oxidize among the examined compounds and the third easiest to reduce. In addition, the 1.62 eV HOMO-LUMO gap of 20 is the smallest of the examined compounds, and this agrees with values calculated using the DFT method. Spectroelectrochemical measurements afforded UV-visible absorption spectra for both the radical cations and radical anions of the examined chlorins. The ring-B reduced compound 20, with a fused six-member N-butylimide ring, is regarded as the most promising candidate in this study for photodynamic therapy because it has the longest wavelength absorption and the largest quantum yield of singlet oxygen formation among the compounds investigated.

Synthesis, Spectroscopic, and in Vitro Photosensitizing Efficacy of Ketobacteriochlorins Derived from Ring-B and Ring-D Reduced Chlorins via Pinacol–Pinacolone Rearrangement

“…31 We have recently reported an efficient regioselective preparation of ring-Band ring-D reduced chlorins from bacteriochlorins. 32 We extended this approach for bacteriopyropheophorbide-a, which on treating with DDQ at room temperature produced mainly D-ring reduced chlorin 5 , whereas on treating 6 with ferric chloride (FeCl 3 ) produced ring-B reduced chlorin 7 in excellent yields (Scheme 2). Analysis of the NMR data confirmed the structures of both isomers.…”

In Vitro Cellular Uptake and Dimerization of Signal Transducer and Activator of Transcription-3 (STAT3) Identify the Photosensitizing and Imaging-Potential of Isomeric Photosensitizers Derived from Chlorophyll-a and Bacteriochlorophyll-a

“…sphaeroides. 29 The reaction sequences followed for the preparation of the desired compounds are shown in Scheme 3. In brief, two approaches were used for the preparation of the intermediate 20.…”

“…Compound 18 29 (100.0 mg, 0.17 mmol, 1.0 equiv) was dissolved in dry CH 2 Cl 2 (15 mL), and HBr gas was bubbled into the solution for 2 min. The reaction mixture was stirred for 5 min at room temperature.…”

Remarkable Regioselective Position-10 Bromination of Bacteriopyropheophorbide-a and Ring-B Reduced Pyropheophorbide-a

“…20 In this report, we present a remarkable regioselective bromination of the ring-B reduced chlorins and bacteriochlorins derived from bacteriochlorophyll- a . Although the syntheses and photophysical properties of the brominated porphyrins and synthetic bacteriochlorins have been investigated, 21 comparatively little is known about the reactivity of naturally occurring chlorins and bacteriochlorins towards halogenation and functionalization.…”

“…20,23 Both chlorins on reacting with NBS or pyridinium bromide gave the corresponding 10-bromo analogs 14 and 16 , respectively. To our surprise, no substitution was observed at position-5 adjacent to reduced ring-B.…”