Ana Filipa R. Cerqueira

An efficient protocol was developed for the microwave-mediated metallation of 5-(4-methoxycarbonylphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin (P1) with bis(benzonitrile)platinum dichloride salt and subsequent 1,3-dipolar cycloaddition of the resulting PtP1 with an azomethine ylide to give two isomeric metallochlorins: PtC1 (main isomer) and PtC3. The methyl ester group of metalloporphyrin PtP1 and metallochlorin PtC1 was successfully hydrolysed in an alkaline medium to yield the corresponding derivatives PtP2 and PtC2 in moderate-to-good yields. As a proof of concept of the reactivity of the carboxy group in PtP2 and PtC2, these compounds were conjugated with a hydroxylated derivative of indomethacin, a known potent non-steroidal anti-inflammatory, obtaining the conjugates PtP2-Ind and PtC2-Ind. The obtained platinum(II) porphyrins and chlorins were characterized by UV-Vis, NMR spectroscopy and mass spectrometry. The structure of PtP1 was also confirmed by X-ray crystallography. Singlet oxygen generation studies were carried out, as well as theoretical calculations, which demonstrated that the prepared Pt(II) complexes can be considered potential photosensitizers for PDT.

A simple and reliable methodology for the detection of paralytic shellfish toxins (PSTs) in bivalve tissues using potentiometric chemical sensors was developed. Five methods of PST extraction from mussel and oyster tissues were evaluated, including the AOAC-recommended method, which served as the reference. The main objective was to minimize the matrix effect of the extracts on the sensors’ responses and ensure efficient toxin recovery. Extraction procedures using acetic acid with heating and water yielded the highest responses from the potentiometric chemical sensors to PSTs. The highest recovery of PSTs from bivalve tissues was achieved with extraction using acetic acid and heating. Further extract purification, which is indispensable for liquid chromatography with fluorometric detection (LC-FLD) analysis, was found to be unnecessary for analysis with chemical sensors. While water extraction can also be used as a rapid and simple PST extraction method, the lower recoveries should be considered when interpreting the results. Further research is needed to identify the compounds remaining in the extracts that cause a decrease in sensor responses and to develop procedures for their elimination.

New β-amino-substituted porphyrin derivatives bearing carboxy groups were synthesized and their performance as sensitizers in dye-sensitized solar cells (DSSC) was evaluated. The new compounds were obtained in good yields (63–74%) through nucleophilic aromatic substitution reactions with 3-sulfanyl- and 4-sulfanylbenzoic acids. Although the electrochemical studies indicated suitable HOMO and LUMO energy levels for use in DSSC, the devices fabricated with these compounds revealed a low power conversion efficiency (PCE) that is primarily due to the low open-circuit voltage (V_oc) and short-circuit current density (J_sc) values.

Indomethacin is a potent non-steroidal anti-inflammatory drug (NSAID) with a strong selective inhibitor activity towards cyclooxygenase-2 (COX-2), an enzyme that is highly overexpressed in various tumour cells, being involved in tumourigenesis. Concomitantly, porphyrins have gained much attention as promising photosensitizers (PSs) for the non-invasive photodynamic therapy (PDT) of cancer. Herein, we report the design, and determine the singlet oxygen generation capacity and in vitro cellular toxicity of porphyrin– and chlorin–indomethacin conjugates (P2-Ind and C2-Ind). Both the conjugates were obtained in high yields and were characterized by ¹H, ¹⁹F and ¹³C NMR as well as by high resolution mass spectrometry. The singlet oxygen generation properties were assessed by the 1,3-diphenylisobenzofuran singlet oxygen trap method, which showed that C2 and C2-Ind are the best singlet oxygen photosensitizers. In addition, it was found that the presence of indomethacin did not influence the singlet oxygen generation of porphyrin or chlorin. Cytotoxicity studies of the conjugate in human HEp2 cells revealed that the porphyrin– and chlorin–indomethacin conjugates have similar dark cytotoxicities, while chlorin C2 was shown to be the most phototoxic. Despite having lower cellular uptake than C2-Ind after 24 hours, chlorin C2 had a broad localization in HEp2 cells while the chlorin–indomethacin conjugate C2-Ind could be detected in the form of small aggregates. DFT calculations were performed to shed light on the reaction energy involved in the formation of the indomethacin conjugates and to compare the relative stability of selected isomers in solution. Moreover, the calculated energy of their first excited triplet state structures confirmed their use as suitable photosensitizers to generate singlet oxygen for PDT.

The reaction of meso-tetrakis(pentafluorophenyl)porpholactone with azomethine ylides and nitrones affords pyrrolidine-fused and isoxazolidine-fused dihydroporpholactones that display, respectively, isobacteriochlorin- and chlorin-type UV–Vis spectra. These reactions are site-selective, yielding, respectively, 17,18- or 12,13-dihydroporpholactones. The crystal and molecular features of pyrrolidine-fused and isoxazolidine-fused dihydroporpholactones were unveiled from single-crystal X-ray diffraction studies.

Porphyrins bearing formyl or vinyl groups have been explored as starting materials to prepare new compounds with adequate features for different applications. In this review it is discussed mainly synthetic strategies based on the reaction of meso-tetraarylporphyrins bearing those groups at β-pyrrolic positions. The use of some of the obtained porphyrin derivatives for further transformations, namely via pericyclic reactions, is also highlighted.

This review covers the synthesis of coumarin–porphyrin, coumarin–phthalocyanine and coumarin–corrole conjugates and their potential applications. While coumarin–phthalocyanine conjugates were obtained almost exclusively by tetramerization of coumarin-functionalized phthalonitriles, coumarin–porphyrin and coumarin–corrole conjugates were prepared by complementary approaches: (a) direct synthesis of the tetrapyrrolic macrocycle using formylcoumarins and pyrrole or (b) by functionalization of the tetrapyrrolic macrocycle. In the last approach a range of reaction types were used, namely 1,3-dipolar cycloadditions, hetero-Diels–Alder, Sonogashira, alkylation or acylation reactions. This is clearly a more versatile approach, leading to a larger diversity of conjugates and allowing the access to conjugates bearing one to up to 16 coumarin units.