Synthesis of New Chlorin e₆Trimethyl and Protoporphyrin IX Dimethyl Ester Derivatives and Their Photophysical and Electrochemical Characterizations

Abstract

In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin e6 trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the β-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications.

Antimicrobial Photodynamic Therapy against Endodontic Enterococcus faecalis and Candida albicans Mono and Mixed Biofilms in the Presence of Photosensitizers: A Comparative Study with Classical Endodontic Irrigants

“…This formulation is available in the dentistry market with a light source device (FotoSan ® : 630, CMS Dental A/S, Glyngore, Roslev, Denmark) (Rios et al, 2011). The cationic porphyrin TMPyP and the modified chlorophyll, Zn(II)e 6 Me, were synthetized and isolated according to the literature (Carvalho et al, 2010; Menezes et al, 2014). Their 1 H NMR and UV–vis spectra were consistent with literature data and their purity was confirmed by thin layer chromatography and 1 H NMR (data not shown).…”

The Red Color of Life Transformed – Synthetic Advances and Emerging Applications of Protoporphyrin IX in Chemical Biology

“…A combined Knoevenagel hetero Diels‐Alder reaction on the vinyl groups of Zn complex 11 [Zn(II)PPIX‐dme] with coumarin, quinolone, and naphthoquinoline derivatives was carried out in order to obtain new photosensitizer‐natural product conjugates, e.g. 33a and 33b (Scheme ) …”

β-Formyl- and β-Vinylporphyrins: Magic Building Blocks for Novel Porphyrin Derivatives

“…The extension of this hetero-Diels–Alder approach to the zinc(II) complexes of chlorin e 6 trimethyl ester and protoporphyrin-IX as dienophiles and the ortho -quinone methides 63 , 64 and the ones generated from 4-hydroxy- N -methylquinolin-2-one and 2-hydroxy-1,4-naphthoquinone and paraformaldehyde, afforded the adequate dyads 71 and 72 in excellent yields (81–91%) ( Figure 14 ) [ 139 ]. These complexes and the corresponding free-bases obtained from demetallation were isolated as mixtures of diastereomers and their abundances and characterization were determined by NMR.…”

“… Compounds obtained from the reaction of natural-type porphyrin derivatives with ortho -quinone methides [ 139 ]. …”