Characterization of Porphyrins, Chlorins, and Bacteriochlorins Formed via Allomerization of Bacteriochlorophylla. Synthesis of Highly Stable Bacteriopurpurinimides and Their Metal Complexes

Abstract

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.

Synthesis and Characterization of Mono-, Di-, and Tri-Poly(ethylene glycol) Chlorin e6 Conjugates for the Photokilling of Human Ovarian Cancer Cells

“…Higher solubility chlorins were easier to purify, as has been noted by others as well. 6 LCMS data indicated that 1 contained one PEG group (MS calcd for C 41 H 51 N 4 O 9 [M+H] + = 743.3651, found 743.3673), 2 contained two PEG groups (MS calcd for C 48 H 65 N 4 O 12 [M+H] + = 889.4593, found 889.4586), and 3 contained three PEG groups (MS calcd for C 55 H 79 N 4 O 15 [M+H] + = 1035.5536, found 1035.5538). LCMS provided mass identification for 1–3 but gave no information about structure.…”

Evaluation of Bacteriochlorophyll-Reconstituted Low-Density Lipoprotein Nanoparticles for Photodynamic Therapy Efficacy In Vivo

“…Bchl-CE was synthesized via a multistep procedure: Bchl was extracted from R. sphaeroides and was hydrolyzed in dilute HCl to generate the key starting material, Bchl-acid [19]. Esterification of Bchl-acid using diazomethane yielded bacteriopheophorbide a methyl ester in high yield.…”

“…Bacteriopheophorbide a (Bchl-acid, see FIGURE 2A) was synthesized from Bchl extracted from R. sphaeroides in an inert atmosphere using 1-propanol following literature methods [19]. …”

Nanotechnology for photodynamic therapy: a perspective from the Laboratory of Dr. Michael R. Hamblin in the Wellman Center for Photomedicine at Massachusetts General Hospital and Harvard Medical School

“…He also develops models for photosynthetic reaction centers [70] and deeply explores the chemistry of porphyrin-based compounds related to chlorins and bacteriochlorins [71]. Most of the PSs and tumor-imaging agents developed in his group are derived from naturally occurring chlorophyll-a and bacteriochlorophyll-a [72]. One of his compounds (HPPH) is currently in phase II human clinical trials [73], and several more are in various stages of preclinical and toxicological studies.…”