Synthesis of cationic water-soluble esters of chlorin e6

Two esters of chlorin e₆ have been synthesized by esterification with aminoalcohols via the formation of acid chloride using oxalyl chloride and converted to the corresponding cationic water-soluble esters of chlorin e₆. The visible absorption and circular dichroism spectra have revealed that these two cationic chlorin e₆ esters synthesized are readily soluble in water as a monomer.     

Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. II. Derivatization

Stable chlorins bearing few or no substituents have been subjected to a variety of reactions including demetalation, magnesium insertion, oxochlorin formation, and bromination followed by Suzuki coupling. The kinetics of deuteration also have been determined for two oxochlorins and a series of chlorins bearing 0, 1, 2, or 3 meso-aryl substituents.     

Sparsely substituted chlorins as core constructs in chlorophyll analogue chemistry. I. Synthesis

Five routes to stable chlorins bearing 0 or 1 meso substituents have been investigated, among which reaction of a 9-bromo-1-formyldipyrromethane and 2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin proved most effective. Application of this route afforded metallochlorins [Cu(II), Zn(II), and Pd(II)] including the chlorin lacking any β-pyrrole and meso substituents.     

Synthesis of Derivatives of Chlorin P6 Trimethyl Ester

The Vilsmeier reaction of nickel(II) chlorin P₆ trimethyl ester with 3-dimethyl-aminoacrolein yielded nickel(II) chlorin P₆ 20-(2-formylvinyl) trimethyl ester and nickel(II) chlorin P₆ 3-(1-hydroxyethyl)-3-devinyl-20-(2-formylvinyl) trimethyl ester. Also, the outgrowths of nickel(II) chlorin P₆ 20-(2-formyl) trimethyl ester and nickel(II) chlorin P₆ 3-(2-formylvinyl)-3-devinyl-20-(2-formyl) trimethyl ester were obtained by Vilsmeier reaction with dimethylformamide. By treating the derivatives of nickel(II) 20-(2-formyl)-chlorin and nickel(II) 3-(2-formylvinyl)-20-(2-formyl)-chlorin with trifluoracetic acid, the removal of the central nickel(II) ion was accomplished. The derivatives of 20-(2-formyl)-chlorin and 3-(2-formylvinyl)-20-(2-formyl)-chlorin demonstrated considerable bathochromic shift of the major absorption band in the red region of the optical spectrum.     

Beyond green with synthetic chlorophylls – Connecting structural features with spectral properties

The distinct features of chlorophylls in photosynthesis have led to the formation of numerous derivatives for applications encompassing solar energy conversion, molecular photonics, photodynamic therapy, and molecular imaging. Synthetic chlorins created de novo and bearing a geminal dimethyl group in the reduced ring have proved invaluable for fundamental studies. Four decades of research have led to accumulation of tabulated spectra for > 400 such synthetic chlorins with distinct structural frameworks (17-oxochlorins, 13¹-oxophorbines, chlorinimides) and substituents (alkyl, aryl, ethynyl, phenylethynyl, acetyl, formyl) located at specific (meso, β) positions. In this review, spectral traces (324 absorption, 247 fluorescence) are assembled along with photophysical data including the molar absorption coefficient (ε), fluorescence quantum yield (Φ_f) and singlet excited-state lifetime (τ_s). The review uses the accumulated spectral data derived from chlorins all containing a uniform molecular scaffold to (1) highlight the effects of molecular structure on spectral features, and (2) identify trends including how ε, Φ_f and τ_s vary with wavelength and other features. Use of a common geminal-dimethyl-substituted chlorin scaffold – beginning with no substituents, to one substituent at designated sites, and to 2 or more substituents – provides a systematic Aufbau approach for understanding the absorption spectra of chlorins on a path to and beyond the native chlorophylls. The review provides insights concerning the rational design of potent analogues of Nature’s preeminent red-region absorbers for potential utilization in diverse applications and is aimed at multiple audiences: those interested in spectral properties, tetrapyrrole photophysics, and the molecular design of new chromophores.     

Amino acid derivatives of pyropheophorbide-α ethers as photosensitizer: Synthesis and photodynamic activity

Ten new water-soluble amino acid conjugates of pyropheophorbide-α ethers 4a-4j were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compounds exhibited higher phototoxicity and lower dark toxicity against three kinds of tumor cell lines than BPD-MA. In particular, themost phototoxic compound 4d and 4j individually showed IC₅₀ values of 41 nmol/L and 33 nmol/L against HCT116 cell, which represented 7.8- and 9.7-fold increase of antitumor potency compared to BPD-MA, respectively, suggesting that they were promising photosensitizers for PDT applications because of their strong absorption at long wavelength (λ_max>650 nm), high phototoxicity, low dark cytotoxicity and good water-solubility.     

Controlled porphyrinogen oxidation for the selective synthesis of meso-tetraarylchlorins

Chlorins have been synthesized through the reduction of the corresponding porphyrins although theoretically they can be obtained from reduced macrocycle forms as porphyrinogens. A new method for the oxidation of meso-tetraarylporphyrinogens was developed generating a substantial amount of chlorin relatively to porphyrin. The structure of the porphyrinogen, particularly the presence of substituents on the meso-phenyl groups, is decisive for the final yield of chlorin. In the case of meso-tetrakis(2,6-dichlorophenyl)porphyrinogen, 92% of the corresponding chlorin is obtained.     

Design and photophysical properties of new RGD targeted tetraphenylchlorins and porphyrins

The synthesis, characterization, fluorescence, and singlet oxygen quantum yields of tetraphenylporphyrin and tetraphenylchlorin coupled to RGD type peptide are reported. C-terminus protected RGD derivatives were synthesized in liquid phase at the gram scale via an efficient convergent process. C-terminus unprotected RGD derivatives were synthesized on solid support. The UV-vis, fluorescence, and singlet emission spectra showed that the photophysical properties of the photosensitizers were retained in all compounds and some of them are very promising for potential PDT applications.     

A facile synthesis of cyano-chlorins related to chlorophyll from formyl (pyro)-pheophorbide-α by a tandem transformation of the aldehyde into a nitrile group

A facile synthesis for cyanochlorin related to chlorophyll from a formyl-substituted chlorin, by the oxidation ofmethyl (pyro)pheophorbide-α, was accomplished. These readily available chlorin aldehydes were assembled together with hydroxylamine hydrochloride in a tandem process to produce the corresponding chlorin nitriles inmoderate to good yields. The formation of chlorin nitrile was discussed and a possible mechanism for the corresponding cyanation reaction was tentatively proposed.     

Convenient peripheral aroyloxylation reactions of porphyrins and chlorophyll-a-based chlorins with benzoyl peroxide

A practical and efficient methodology for the formation of C–O bonds on the porphyrin/chlorin periphery was developed. The aroyloxy-substituted porphyrins and chlorins related to chlorophyll-a at the β- and meso-positions, respectively, were conveniently synthesized by the free radical substitution reaction with benzoyl peroxide and its homologs.