Porphyrin–Coumarin Dyads: Investigation of Photophysical Properties and DNA Interactions

Abstract

Two new nonconjugated porphyrin-coumarin dyads with different orientations with respect to donor-acceptor entities and their zinc complexes were synthesized. Single-crystal structures of the free-base porphyrin-coumarin dyads were successfully resolved. The absorption spectra of the dyads were linear combinations of the spectra of their corresponding monomers, indicating a negligible electronic communication between the coumarin and porphyrin moieties. However, the fluorescence emission of the coumarin entity in all of the dyads was quenched significantly compared to that of pristine coumarin, and this effect was attributed to intramolecular energy transfer from the coumarin to the porphyrin. The energy transfer kinetics from the coumarin to the porphyrin was shown to be fast ( k = 1.13 × 10 s for the ortho-isomer and 5.13 × 10 s for the para-isomer in DMF) and efficient (transfer efficiency ca. 96-97%). Transient absorption studies showed that the excited state decay process (S → S*, S* → S, S → S, and S → T) of the para-isomer was faster than that of the ortho-isomer in DMF. All of the synthesized dyads were tested for their interactions with ct-DNA and photocleavage activity toward PBR322-DNA. The results revealed that all of the dyads interacted with ct-DNA via only an external groove-binding mode; the binding constants were calculated to be 3.24 × 10 (3a), 3.05 × 10 (3b), 3.04 × 10 (4a), and 4.88 × 10 (4b), and the photocleavage activity was in the order 4b < 3b < 4a < 3a. Furthermore, only the zinc complexes of the porphyrin-coumarin dyads could be absorbed by tumor cells (A549). These complexes were mainly localized in the cytoplasm, exhibited red fluorescence, and showed low cytotoxicity toward all of the tumor cell lines tested. The results showed that these zinc complexes of the porphyrin-coumarin dyads have potential applications in fluorescence imaging.

A Coumarin–Porphyrin FRET Break-Apart Probe for Heme Oxygenase-1

“…Alkylation of 6 with 7 was achieved in DMF at room temperature over 5 d with potassium carbonate as the base in a procedure adapted from Wang and Liu. 39 Complexation of 8 with FeCl 2 ·4H 2 O in chloroform/methanol (3:1) and methyl ester hydrolysis under basic conditions gave rise to the formation of complex Fe–L 1 . Ester hydrolysis after metal complexation was found to be much more effective.…”

“…Such a high efficiency supports the literature precedent of an efficient intramolecular energy transfer between coumarin donor and porphyrin acceptor fluorophores. 38 , 39 …”

“…Complex Fe–L 2 is based on the structure of HP-TPP, and the subsequent Zn-complex has been previously synthesized by Liu and co-workers. 39 In our study, the Fe complex was of greater interest, however, as Zn-porphyrins such as zinc protoporphyrin (ZnPP) are known to inhibit hHO-1 activity. 45 As the structure of Fe–L 2 differs significantly from biologically relevant Fe-PPIX, it will provide an additional insight into the structural requirements to maintain HO-1 activity.…”

“… 38 In contrast, Liu and co-workers developed a Zn–coumarin–porphyrin FRET probe based on 5-(4-hydroxyphenyl)-10,15,20-triphenyl porphyrin (HP-TPP) and monitored the binding properties to DNA. 39 …”

Synthesis and Biological Properties of Coumarin Derivatives. A Review

“…The corresponding free-base porphyrins analogues were successfully obtained in the presence of concentrated hydrochloric acid in chloroform at room temperature in good yields, Scheme 76. [103] Lately, Tekuri and co-workers [104] described the synthesis of nickel, copper and zinc complexes of coumarin-fused pyrido [2,3-b]porphyrins via one-pot reaction from 2-amino-mesotetraphenylporphyrin, aromatic aldehydes and 4-hydroxycoumarin., Scheme 77. The preliminary photophysical study of meso-tetraphenyl-porphyrin precursors showed a significant redshift in their electronic absorption and emission spectra.…”