{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:20:49Z","timestamp":1768454449975,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSF (Chemical Research Instrument Fund)","award":["CHE0741968"],"award-info":[{"award-number":["CHE0741968"]}]},{"name":"NSF (Chemical Research Instrument Fund)","award":["S10RR025636"],"award-info":[{"award-number":["S10RR025636"]}]},{"name":"NIH Shared Instrument Grant","award":["CHE0741968"],"award-info":[{"award-number":["CHE0741968"]}]},{"name":"NIH Shared Instrument Grant","award":["S10RR025636"],"award-info":[{"award-number":["S10RR025636"]}]},{"name":"Academic Senate of UC San Diego","award":["CHE0741968"],"award-info":[{"award-number":["CHE0741968"]}]},{"name":"Academic Senate of UC San Diego","award":["S10RR025636"],"award-info":[{"award-number":["S10RR025636"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Petrosamine (1)\u2014a colored pyridoacridine alkaloid from the Belizean sponge, Petrosia sp., that is also a potent inhibitor of acetylcholine esterase (AChE)\u2014was investigated by spectroscopic and computational methods. Analysis of the petrosamine-free energy landscapes, pKa and tautomerism, revealed an accurate electronic depiction of the molecular structure of 1 as the di-keto form, with a net charge of q = +1, rather than a dication (q = +2) under ambient conditions of isolation-purification. The pronounced solvatochromism (UV-vis) reported for 1, and related analogs were investigated in detail and is best explained by charge delocalization and stabilization of the ground state (HOMO) of 1 rather than an equilibrium of competing tautomers. Refinement of the molecular structure 1 by QM methods complements published computational docking studies to define the contact points in the enzyme active site that may improve the design of new AChE inhibitors based on the pyridoacridine alkaloid molecular skeleton.<\/jats:p>","DOI":"10.3390\/md21080446","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T12:10:23Z","timestamp":1691755823000},"page":"446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Petrosamine Revisited. Experimental and Computational Investigation of Solvatochromism, Tautomerism and Free Energy Landscapes of a Pyridoacridinium Quaternary Salt"],"prefix":"10.3390","volume":"21","author":[{"given":"Christopher J.","family":"Gartshore","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive MC3568, La Jolla, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive MC3568, La Jolla, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive MC3568, La Jolla, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadeusz F.","family":"Molinski","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, 9500 Gilman Drive MC3568, La Jolla, San Diego, CA 92093, USA"},{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 9500 Gilman Drive MC3568, La Jolla, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1021\/jo00241a049","article-title":"Petrosamine, a Novel Pigment from the Marine Sponge Petrosia sp","volume":"53","author":"Molinski","year":"1988","journal-title":"J. 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