Design, Synthesis, and Photophysical Characterization of Water-Soluble Chlorins

• Published in: Journal of organic chemistry Vol. 73; no. 8; pp. 3145 - 3158
• Main Authors: Borbas, K. Eszter, Chandrashaker, Vanampally, Muthiah, Chinnasamy, Kee, Hooi Ling, Holten, Dewey, Lindsey, Jonathan S.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 18.04.2008; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Molecular Structure; Organic chemistry; Photochemistry; Physical Sciences; Porphyrins - chemical synthesis; Porphyrins - chemistry; Preparations and properties; Science & Technology; Solubility; Spectrophotometry; Water - chemistry; OXIDE; CORE CONSTRUCTS; PHOTOSENSITIZERS; STATE; PORPHYRINS BEARING; PART 1; CHLOROPHYLL ANALOG CHEMISTRY; FLOW-CYTOMETRY; ACID TETHERS; SPARSELY SUBSTITUTED CHLORINS; Water; Fluorescence; NMR spectrometry; Derivatization; Solubilization; Phosphorus Organic compounds; Characterization; Chemical reduction; Triplet state; Geminal compound; Optical properties; Chlorins; Water solubility; Chemical synthesis; Protection; Protecting group; Toluene; Solubility; Hydrophobic compound; Singlet state; Organic phosphonate; Buffer system; Time resolution; Absorption spectrometry; Fluorophore; Fluorescence yield; Porphyrin; Organic phosphate; Aqueous solution; Spectrophotometry; Photosensitizer; Saline solution; Room temperature; Excited state; Ultraviolet visible spectrometry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo7026728

The use of chlorins as photosensitizers or fluorophores in a range of biological applications requires facile provisions for imparting high water solubility. Two free base chlorins have been prepared wherein each chlorin bears a geminal dimethyl group in the reduced ring and a water-solubilizing unit at the chlorin 10-position. In one design (FbC1-PO 3 H 2 ), the water-solubilizing unit is a 1,5-diphosphonopent-3-yl (“swallowtail”) unit, which has previously been used to good effect with porphyrins. In the other design (FbC2-PO 3 H 2 ), the water-solubilizing unit is a 2,6-bis(phosphonomethoxy)phenyl unit. Two complementary routes were developed for preparing FbC2-PO 3 H 2 that entail introduction of the protected phosphonate moieties either in the Eastern-half precursor to the chlorin or by derivatization of an intact chlorin. Water-solubilization is achieved in the last step of each synthesis upon removal of the phosphonate protecting groups. The chlorins FbC1-PO 3 H 2 and FbC2-PO 3 H 2 are highly water-soluble (>10 mM) as shown by 1H NMR spectroscopy (D2O) and UV−vis absorption spectroscopy. The photophysical properties of the water-soluble chlorins in phosphate-buffered saline solution (pH 7.4) at room temperature were investigated using static and time-resolved absorption and fluorescence spectroscopic techniques. Each chlorin exhibits dominant absorption bands in the blue and the red region (λ = 398, 626 nm), a modest fluorescence yield (Φf ≈ 0.11), a long singlet excited-state lifetime (τ = 7.5 ns), and a high yield of intersystem crossing to give the triplet state (Φisc = 0.9). The properties of the water-soluble chlorins in aqueous media are comparable to those of hydrophobic chlorins in toluene. The high aqueous solubility combined with the attractive photophysical properties make these compounds suitable for a wide range of biomedical applications.