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A photosensitizer prerequisite is significant absorption of biocompatible light in the visible\/near IR range, ideally between 600 and 1000\u00a0nm. We use highly accurate multiconfigurational CASSCF\/MS-CASPT2\/MM and TD-DFT methodologies to determine the absorption properties of a series of gemcitabine derivatives with the goal of red-shifting the UV absorption band toward the visible region and facilitating triplet state population. The choice of the substitutions and, thus, the rational design is based on important biochemical criteria and on derivatives whose synthesis is reported in the literature. The modifications tackled in this paper consist of: (i) substitution of the oxygen atom at O2 position with heavier atoms (O \u2192 S and O \u2192 Se) to red shift the absorption band and increase the spin\u2013orbit coupling, (ii) addition of a lipophilic chain at the N7 position to enhance transport into cancer cells and slow down gemcitabine metabolism, and (iii) attachment of aromatic systems at C5 position to enhance red shift further. Results indicate that the combination of these three chemical modifications markedly shifts the absorption spectrum toward the 500\u00a0nm region and beyond and drastically increases spin\u2013orbit coupling values, two key PDT requirements. The obtained theoretical predictions encourage biological studies to further develop this anticancer approach.<\/jats:p>","DOI":"10.1063\/5.0170949","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T11:06:53Z","timestamp":1702292813000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Electronic spectroscopy of gemcitabine and derivatives for possible dual-action photodynamic therapy applications"],"prefix":"10.1063","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-0469","authenticated-orcid":false,"given":"Abdelazim M. 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