{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:07:52Z","timestamp":1789348072613,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:p>\n                    In this study, we present a comprehensive structural analysis of four distinct chemical libraries: FDA\u2010approved drugs, blood\u2010brain barrier (BBB) permeable agents, natural products (UNPDA), and human metabolites. Our multidimensional profiling reveals fundamental divergences in molecular architecture. While synthetic drugs (FDA) and CNS\u2010active agents (BBB) follow continuous, Gaussian\u2010like distributions for carbon hybridization, natural products exhibit biosynthetic quantization, discrete, high\u2010intensity abundance spikes at C19 and C30, corresponding to steroid and triterpene scaffolds. Stereochemical analysis identifies a chirality\u2010structure lock in natural products, where stereoisomer density peaks significantly at these same integers (Avg. 3.53 isomers\/mol), a complexity feature absent in the diffuse distribution of synthetic libraries. Topologically, we identify hyper\u2010globularity as a distinct signature for CNS permeability. Radial distribution function (RDF) analysis demonstrates that BBB agents possess a highly compressed aliphatic core, packing 93.2% of their sp\n                    <jats:sup>3<\/jats:sup>\n                    mass within a 3 \u00c5 radius, compared to 84.4% for general FDA therapeutics. Furthermore, elemental profiling reveals a heteroatom gap: synthetic drugs exhibit a high electronegative atom\u2010to\u2010carbon ratio (0.43), whereas BBB agents (0.33) converge with the lipophilic profile of natural products (0.32), suggesting that CNS penetration requires a biomimetic reduction in polarity. These findings establish new quantitative metrics for designing neuro\u2010compatible and biomimetic pharmacophores.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70462","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:26:31Z","timestamp":1787880391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Topological and Spatial Analysis of FDA\u2010Approved Drugs, Blood\u2010Brain Barrier Permeants, Natural Products, and Metabolites"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9300-4147","authenticated-orcid":false,"given":"Vijay H.","family":"Masand","sequence":"first","affiliation":[{"name":"Department of Chemistry Vidya Bharati Mahavidyalaya  Amravati Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami A.","family":"Al\u2010Hussain","sequence":"additional","affiliation":[{"name":"Chemistry Department College of Science Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1781-0236","authenticated-orcid":false,"given":"Mohammed Sharique Ahmed","family":"Quadri","sequence":"additional","affiliation":[{"name":"Department of Basic medical sciences College of Medicine Almaarefa University  Dariyah Saudi Arabia"},{"name":"Research Center Deanship of Scientific Research and Post\u2010Graduate Studies Almaarefa University  Dariyah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6518-6131","authenticated-orcid":false,"given":"Abdul","family":"Samad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Tishk International University  Erbil Kurdistan Region Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-9202","authenticated-orcid":false,"given":"Magdi E. 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