New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation

An efficient protocol was developed for the microwave-mediated metallation of 5-(4-methoxycarbonylphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin (<b>P1</b>) with bis(benzonitrile)platinum dichloride salt and subsequent 1,3-dipolar cycloaddition of the resulting <b>PtP1</b> with an azomethine ylide to give two isomeric metallochlorins: <b>PtC1</b> (main isomer) and <b>PtC3</b>. The methyl ester group of metalloporphyrin <b>PtP1</b> and metallochlorin <b>PtC1</b> was successfully hydrolysed in an alkaline medium to yield the corresponding derivatives <b>PtP2</b> and <b>PtC2</b> in moderate-to-good yields. As a proof of concept of the reactivity of the carboxy group in <b>PtP2</b> and <b>PtC2</b>, these compounds were conjugated with a hydroxylated derivative of indomethacin, a known potent non-steroidal anti-inflammatory, obtaining the conjugates <b>PtP2</b>-<b>Ind</b> and <b>PtC2</b>-<b>Ind</b>. The obtained platinum(II) porphyrins and chlorins were characterized by UV-Vis, NMR spectroscopy and mass spectrometry. The structure of <b>PtP1</b> 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.