{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:11:00Z","timestamp":1791634260975,"version":"4.3.4"},"reference-count":50,"publisher":"AIP Publishing","issue":"15","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIN","award":["2022AN47CA"],"award-info":[{"award-number":["2022AN47CA"]}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,21]]},"abstract":"<jats:p>The effects of the incorporation of oxygen, sulfur, selenium, and tellurium into the porphyrin core over nitrogen have been explored using density functional theory (DFT) and its time-dependent and quadratic response implementations (TDDFT and QR-TDDFT). The aim was to investigate how substitution affects the photophysical properties of these dyes and how such modifications could make them more suitable to be proposed as heavy-atom-free agents in photodynamic therapy (PDT). The photophysical properties assessed in our investigation, relevant for the PDT mechanism, allow us to establish that chalcogens trigger beneficial bathochromic shifts enabling the achievement of more biocompatible wavelengths while enhancing spin\u2013orbit coupling and kinetic constants for intersystem crossings. Considering the higher safety profile of sulfur in biological systems and the numerous studies highlighting the role of Se-containing materials in inducing apoptosis in cancer cells with minimal side effects on normal cells, we believe that the results presented here on both the S- and Se-heterosubstitution strategies could be highly promising.<\/jats:p>","DOI":"10.1063\/5.0272734","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T10:41:51Z","timestamp":1760524911000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Evaluation of sulfur and selenium substituents to induce the heavy atom effect in metal-free porphyrins"],"prefix":"10.1063","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7288-7833","authenticated-orcid":false,"given":"Wichien","family":"Sang-aroon","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Engineering, Rajamangala University of Technology Isan 1 , KhonKaen Campus, KhonKaen 40000,","place":["Thailand"]},{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria 2 , 87036 Rende,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8832-7387","authenticated-orcid":false,"given":"Alessandra Gilda","family":"Ritacca","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria 2 , 87036 Rende,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marirosa","family":"Toscano","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria 2 , 87036 Rende,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9925-7233","authenticated-orcid":false,"given":"Marta Erminia","family":"Alberto","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria 2 , 87036 Rende,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3826-3386","authenticated-orcid":false,"given":"Nino","family":"Russo","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Tecnologie Chimiche, Universit\u00e0 della Calabria 2 , 87036 Rende,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"issue":"9","key":"2025101506413841200_c1","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1021\/acs.accounts.1c00114","article-title":"Bioinspired applications of porphyrin derivatives","volume":"54","year":"2021","journal-title":"Acc. Chem. Res."},{"key":"2025101506413841200_c2","doi-asserted-by":"publisher","first-page":"213157","DOI":"10.1016\/j.ccr.2019.213157","article-title":"Applications of porphyrins in emerging energy conversion technologies","volume":"407","year":"2020","journal-title":"Coord. Chem. Rev."},{"issue":"2","key":"2025101506413841200_c3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00214-015-1794-4","article-title":"22\u03c0-electrons [1.1.1.1.1] pentaphyrin as a new photosensitizing agent for water disinfection: Experimental and theoretical characterization","volume":"135","year":"2016","journal-title":"Theor. Chem. Acc."},{"issue":"1","key":"2025101506413841200_c4","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jphotochemrev.2011.06.001","article-title":"Current states and future views in photodynamic therapy","volume":"12","year":"2011","journal-title":"J.\u00a0Photochem. Photobiol., C"},{"issue":"4","key":"2025101506413841200_c5","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1111\/php.12716","article-title":"Type I and type II photosensitized oxidation reactions: Guidelines and mechanistic pathways","volume":"93","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"2025101506413841200_c6","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/s0010-8545(02)00034-6","article-title":"Photosensitized singlet oxygen and its applications","volume":"233\u2013234","year":"2002","journal-title":"Coord. Chem. Rev."},{"issue":"23","key":"2025101506413841200_c7","doi-asserted-by":"publisher","first-page":"6488","DOI":"10.1039\/c6cs00616g","article-title":"Overcoming the Achilles\u2019 heel of photodynamic therapy","volume":"45","year":"2016","journal-title":"Chem. Soc. Rev."},{"issue":"11","key":"2025101506413841200_c8","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1007\/s43630-021-00102-1","article-title":"Photodynamic disinfection and its role in controlling infectious diseases","volume":"20","year":"2021","journal-title":"Photochem. Photobiol. Sci."},{"key":"2025101506413841200_c9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.20517\/2394-4722.2018.83","article-title":"Photodynamic therapy in cancer treatment - An update review","volume":"5","year":"2019","journal-title":"J.\u00a0Cancer Metastasis Treat."},{"issue":"17","key":"2025101506413841200_c10","doi-asserted-by":"publisher","first-page":"4447","DOI":"10.3390\/cancers13174447","article-title":"Photodynamic therapy: A compendium of latest reviews","volume":"13","year":"2021","journal-title":"Cancers"},{"issue":"18","key":"2025101506413841200_c11","doi-asserted-by":"publisher","first-page":"4853","DOI":"10.1016\/j.bmc.2004.07.011","article-title":"Photodynamic effects of porphyrin and chlorin photosensitizers in human colon adenocarcinoma cells","volume":"12","year":"2004","journal-title":"Bioorg. Med. Chem."},{"issue":"1","key":"2025101506413841200_c12","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1021\/jm9007278","article-title":"Porphyrin\u2013cyclodextrin conjugates as a nanosystem for versatile drug delivery and multimodal cancer therapy","volume":"53","year":"2010","journal-title":"J.\u00a0Med. Chem."},{"issue":"5","key":"2025101506413841200_c13","doi-asserted-by":"publisher","first-page":"e202112236","DOI":"10.1002\/anie.202112236","article-title":"Clinical development of metal complexes as photosensitizers for photodynamic therapy of cancer","volume":"61","year":"2022","journal-title":"Angew. Chem., Int. Ed."},{"issue":"2","key":"2025101506413841200_c14","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1021\/acs.chemrev.8b00211","article-title":"Transition metal complexes and photodynamic therapy from a tumor-centered approach: Challenges, opportunities, and highlights from the development of TLD1433","volume":"119","year":"2019","journal-title":"Chem. Rev."},{"issue":"18","key":"2025101506413841200_c15","doi-asserted-by":"publisher","first-page":"8317","DOI":"10.1021\/jacs.2c02475","article-title":"Intraligand excited states turn a ruthenium oligothiophene complex into a light-triggered ubertoxin with anticancer effects in extreme hypoxia","volume":"144","year":"2022","journal-title":"J.\u00a0Am. Chem. Soc."},{"issue":"36","key":"2025101506413841200_c16","doi-asserted-by":"publisher","first-page":"9784","DOI":"10.1039\/d0sc03008b","article-title":"Breaking the barrier: An osmium photosensitizer with unprecedented hypoxic phototoxicity for real world photodynamic therapy","volume":"11","year":"2020","journal-title":"Chem. Sci."},{"issue":"22","key":"2025101506413841200_c17","doi-asserted-by":"publisher","first-page":"16341","DOI":"10.1021\/acs.inorgchem.0c02137","article-title":"Os(II) oligothienyl complexes as a hypoxia-active photosensitizer class for photodynamic therapy","volume":"59","year":"2020","journal-title":"Inorg. Chem."},{"issue":"21","key":"2025101506413841200_c18","doi-asserted-by":"publisher","first-page":"9735","DOI":"10.1021\/acs.inorgchem.3c04382","article-title":"Ru(II) oligothienyl complexes with fluorinated ligands: Photophysical, electrochemical, and photobiological properties","volume":"63","year":"2024","journal-title":"Inorg. Chem."},{"issue":"51","key":"2025101506413841200_c19","doi-asserted-by":"publisher","first-page":"21181","DOI":"10.1021\/acs.inorgchem.3c03216","article-title":"Ru(II) phenanthroline-based oligothienyl complexes as phototherapy agents","volume":"62","year":"2023","journal-title":"Inorg. Chem."},{"issue":"9","key":"2025101506413841200_c20","doi-asserted-by":"publisher","first-page":"7360","DOI":"10.1021\/jacs.4c15036","article-title":"Ruthenium(II) polypyridyl complexes containing COUBPY ligands as potent photosensitizers for the efficient phototherapy of hypoxic tumors","volume":"147","year":"2025","journal-title":"J.\u00a0Am. Chem. Soc."},{"issue":"3","key":"2025101506413841200_c21","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1039\/d1cs00609f","article-title":"Phototherapeutic anticancer strategies with first-row transition metal complexes: A critical review","volume":"51","year":"2022","journal-title":"Chem. Soc. Rev."},{"issue":"9","key":"2025101506413841200_c22","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.3390\/pharmaceutics13091332","article-title":"Photodynamic therapy review: Principles, photosensitizers, applications, and future directions","volume":"13","year":"2021","journal-title":"Pharmaceutics"},{"issue":"4","key":"2025101506413841200_c23","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.1021\/acs.chemrev.6b00371","article-title":"Chemistry of meso -aryl-substituted expanded porphyrins: Aromaticity and molecular twist","volume":"117","year":"2017","journal-title":"Chem. Rev."},{"issue":"3\u20134","key":"2025101506413841200_c24","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.ccr.2005.10.010","article-title":"Recent developments in heteroporphyrins and their analogues","volume":"250","year":"2006","journal-title":"Coord. Chem. Rev."},{"issue":"21","key":"2025101506413841200_c25","doi-asserted-by":"publisher","first-page":"5968","DOI":"10.1016\/j.bmc.2005.07.006","article-title":"Core-modified porphyrins. Part 5: Electronic effects on photophysical and biological properties in vitro","volume":"13","year":"2005","journal-title":"Bioorg. Med. Chem."},{"issue":"4","key":"2025101506413841200_c26","doi-asserted-by":"publisher","first-page":"3254","DOI":"10.1021\/acs.chemrev.6b00496","article-title":"Heteroatom-containing porphyrin analogues","volume":"117","year":"2017","journal-title":"Chem. Rev."},{"issue":"4","key":"2025101506413841200_c27","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1021\/acs.chemrev.6b00460","article-title":"Synthesis of aza-oxa-and thiaporphyrins and related compounds","volume":"117","year":"2017","journal-title":"Chem. Rev."},{"issue":"31","key":"2025101506413841200_c28","doi-asserted-by":"publisher","first-page":"5167","DOI":"10.1021\/acs.jpca.2c03950","article-title":"Chalcogen effects in the photophysical properties of dimethylamino-1,8-naphthalimide dyes revealed by DFT investigation","volume":"126","year":"2022","journal-title":"J.\u00a0Phys. Chem. A"},{"issue":"41","key":"2025101506413841200_c29","doi-asserted-by":"publisher","first-page":"11113","DOI":"10.1039\/d0sc04747c","article-title":"Thionated organic compounds as emerging heavy-atom-free photodynamic therapy agents","volume":"11","year":"2020","journal-title":"Chem. Sci."},{"issue":"26","key":"2025101506413841200_c30","doi-asserted-by":"publisher","first-page":"6701","DOI":"10.1039\/d0sc02286a","article-title":"Single-atom replacement as a general approach towards visible-light\/near-infrared heavy-atom-free photosensitizers for photodynamic therapy","volume":"11","year":"2020","journal-title":"Chem. Sci."},{"issue":"7","key":"2025101506413841200_c31","doi-asserted-by":"publisher","first-page":"3153","DOI":"10.3390\/molecules28073153","article-title":"Sulphur- and selenium-for-oxygen replacement as a strategy to obtain dual type I\/type II photosensitizers for photodynamic therapy","volume":"28","year":"2023","journal-title":"Molecules"},{"issue":"22","key":"2025101506413841200_c32","doi-asserted-by":"publisher","first-page":"224106","DOI":"10.1063\/5.0170949","article-title":"Electronic spectroscopy of gemcitabine and derivatives for possible dual-action photodynamic therapy applications","volume":"159","year":"2023","journal-title":"J.\u00a0Chem. Phys."},{"key":"2025101506413841200_c33","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1002\/jcc.27331","article-title":"Chalcogen atom effect on the intersystem crossing kinetic constant of oxygen- and sulfur disubstituted heteroporphyrins","volume":"45","year":"2024","journal-title":"J.\u00a0Comput. Chem."},{"issue":"10","key":"2025101506413841200_c34","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s00214-023-03050-4","article-title":"Heavy atom effect through chalcogen substitution in Red Nile dye: A theoretical investigation","volume":"142","year":"2023","journal-title":"Theor. Chem. Acc."},{"issue":"15","key":"2025101506413841200_c35","doi-asserted-by":"publisher","first-page":"3934","DOI":"10.1021\/ol401698n","article-title":"Synthesis of 6-Se-guanosine RNAs for structural study","volume":"15","year":"2013","journal-title":"Org. Lett."},{"issue":"7","key":"2025101506413841200_c36","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.1021\/ja909330m","article-title":"High fidelity of base pairing by 2-selenothymidine in DNA","volume":"132","year":"2010","journal-title":"J.\u00a0Am. Chem. Soc."},{"issue":"3","key":"2025101506413841200_c37","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1039\/c3cp53885k","article-title":"The DNA-forming properties of 6-selenoguanine","volume":"16","year":"2014","journal-title":"Phys. Chem. Chem. Phys."},{"issue":"7","key":"2025101506413841200_c38","doi-asserted-by":"publisher","first-page":"100111","DOI":"10.1016\/j.xcrp.2020.100111","article-title":"Selenium-containing nanomaterials for cancer treatment","volume":"1","year":"2020","journal-title":"Cell Rep. Phys. Sci."},{"key":"2025101506413841200_c39","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/bs.acr.2017.07.007","article-title":"Selenocompounds in cancer therapy: An overview","volume":"136","year":"2017","journal-title":"Adv. Cancer Res."},{"key":"2025101506413841200_c40","volume-title":"Gaussian 16, Revision C.01","year":"2016"},{"issue":"7","key":"2025101506413841200_c41","doi-asserted-by":"publisher","first-page":"5648","DOI":"10.1063\/1.464913","article-title":"Density-functional thermochemistry. III. The role of exact exchange","volume":"98","year":"1993","journal-title":"J.\u00a0Chem. Phys."},{"issue":"2","key":"2025101506413841200_c42","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1103\/physrevb.37.785","article-title":"Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density","volume":"37","year":"1988","journal-title":"Phys. Rev. B"},{"issue":"2","key":"2025101506413841200_c43","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/BF01114537","article-title":"Energy-adjusted ab\u00a0initio pseudopotentials for the second and third row transition elements","volume":"77","year":"1990","journal-title":"Theor. Chim. Acta"},{"issue":"15","key":"2025101506413841200_c44","doi-asserted-by":"publisher","first-page":"154104","DOI":"10.1063\/1.3382344","article-title":"A consistent and accurate ab\u00a0initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu","volume":"132","year":"2010","journal-title":"J.\u00a0Chem. Phys."},{"issue":"8","key":"2025101506413841200_c45","doi-asserted-by":"publisher","first-page":"2999","DOI":"10.1021\/cr9904009","article-title":"Quantum mechanical continuum solvation models","volume":"105","year":"2005","journal-title":"Chem. Rev."},{"issue":"3","key":"2025101506413841200_c46","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/wcms.1172","article-title":"The dalton quantum chemistry program system","volume":"4","year":"2014","journal-title":"Wiley Interdiscip. Rev.: Comput. Mol. Sci."},{"issue":"1\u20132","key":"2025101506413841200_c47","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0009-2614(99)00712-5","article-title":"Internal and external heavy-atom effects on phosphorescence radiative lifetimes calculated using a mean-field spin\u2013orbit Hamiltonian","volume":"310","year":"1999","journal-title":"Chem. Phys. Lett."},{"issue":"2","key":"2025101506413841200_c48","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/wcms.83","article-title":"Spin\u2013orbit coupling and intersystem crossing in molecules","volume":"2","year":"2012","journal-title":"Wiley Interdiscip. Rev.: Comput. Mol. Sci."},{"issue":"1","key":"2025101506413841200_c49","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1021\/ar50001a002","article-title":"Triplet state. Its radiative and nonradiative properties","volume":"1","year":"1968","journal-title":"Acc. Chem. Res."},{"issue":"38","key":"2025101506413841200_c50","doi-asserted-by":"publisher","first-page":"16167","DOI":"10.1039\/c3cp52698d","article-title":"Photophysical origin of the reduced photodynamic therapy activity of temocene compared to Foscan\u00ae: Insights from theory","volume":"15","year":"2013","journal-title":"Phys. Chem. Chem. Phys."}],"container-title":["The Journal of Chemical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.aip.org\/aip\/jcp\/article-pdf\/doi\/10.1063\/5.0272734\/20752787\/155102_1_5.0272734.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.aip.org\/aip\/jcp\/article-pdf\/doi\/10.1063\/5.0272734\/20752787\/155102_1_5.0272734.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T10:41:52Z","timestamp":1760524912000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.aip.org\/jcp\/article\/163\/15\/155102\/3367784\/Evaluation-of-sulfur-and-selenium-substituents-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":50,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2025,10,21]]}},"URL":"https:\/\/doi.org\/10.1063\/5.0272734","relation":{},"ISSN":["0021-9606","1089-7690"],"issn-type":[{"value":"0021-9606","type":"print"},{"value":"1089-7690","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10,21]]},"published":{"date-parts":[[2025,10,15]]},"article-number":"155102"}}