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>...

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Main Authors: José Almeida, Giampaolo Barone, Luís Cunha-Silva, Ana F. R. Cerqueira, Augusto C. Tomé, Maria Rangel, Ana M. G. Silva
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/12/2496
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author José Almeida
Giampaolo Barone
Luís Cunha-Silva
Ana F. R. Cerqueira
Augusto C. Tomé
Maria Rangel
Ana M. G. Silva
author_facet José Almeida
Giampaolo Barone
Luís Cunha-Silva
Ana F. R. Cerqueira
Augusto C. Tomé
Maria Rangel
Ana M. G. Silva
author_sort José Almeida
collection DOAJ
description 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.
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spelling doaj-art-c7a12558cfaf47b7b1de9865b4b360092025-08-20T03:16:23ZengMDPI AGMolecules1420-30492025-06-013012249610.3390/molecules30122496New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen GenerationJosé Almeida0Giampaolo Barone1Luís Cunha-Silva2Ana F. R. Cerqueira3Augusto C. Tomé4Maria Rangel5Ana M. G. Silva6LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto, PortugalDipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Viale delle Scienze, Edificio 17, 90128 Palermo, ItalyLAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, 4169-007 Porto, PortugalLAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalLAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalLAQV-REQUIMTE, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, PortugalLAQV-REQUIMTE, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, PortugalAn 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.https://www.mdpi.com/1420-3049/30/12/2496chlorinsmetallochlorinsplatinum(II) complexesmicrowave-mediated metallationoptical propertiessinglet oxygen generation
spellingShingle José Almeida
Giampaolo Barone
Luís Cunha-Silva
Ana F. R. Cerqueira
Augusto C. Tomé
Maria Rangel
Ana M. G. Silva
New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation
Molecules
chlorins
metallochlorins
platinum(II) complexes
microwave-mediated metallation
optical properties
singlet oxygen generation
title New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation
title_full New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation
title_fullStr New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation
title_full_unstemmed New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation
title_short New Conjugatable Platinum(II) Chlorins: Synthesis, Reactivity and Singlet Oxygen Generation
title_sort new conjugatable platinum ii chlorins synthesis reactivity and singlet oxygen generation
topic chlorins
metallochlorins
platinum(II) complexes
microwave-mediated metallation
optical properties
singlet oxygen generation
url https://www.mdpi.com/1420-3049/30/12/2496
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