{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T14:45:20Z","timestamp":1764859520037,"version":"build-2065373602"},"reference-count":102,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T00:00:00Z","timestamp":1671840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of new congeners, 1-[2-(1-adamantyl)ethyl]-1H-benzimidazole (AB) and 1-[2-(1-adamantyl)ethyl]-4,5,6,7-tetrahalogeno-1H-benzimidazole (Hal=Cl, Br, I; tClAB, tBrAB, tIAB), have been synthesized and studied. These novel multi-target ligands combine a benzimidazole ring known to show antitumor activity and an adamantyl moiety showing anti-influenza activity. Their crystal structures were determined by X-ray, while intermolecular interactions were studied using topological Bader\u2019s Quantum Theory of Atoms in Molecules, Hirshfeld Surfaces, CLP and PIXEL approaches. The newly synthesized compounds crystallize within two different space groups, P-1 (AB and tIAB) and P21\/c (tClAB and tBrAB). A number of intramolecular hydrogen bonds, C\u2212H\u22efHal (Hal=Cl, Br, I), were found in all halogen-containing congeners studied, but the intermolecular C\u2212H\u22efN hydrogen bond was detected only in AB and tIAB, while C\u2212Hal\u22ef\u03c0 only in tClAB and tBrAB. The interplay between C\u2212H\u22efN and C\u2212H\u22efHal hydrogen bonds and a shift from the strong (C\u2212H\u22efCl) to the very weak (C\u2212H\u22efI) attractive interactions upon Hal exchange, supplemented with Hal\u22efHal overlapping, determines the differences in the symmetry of crystalline packing and is crucial from the biological point of view. The hypothesis about the potential dual inhibitor role of the newly synthesized congeners was verified using molecular docking and the congeners were found to be pharmaceutically attractive as Human Casein Kinase 2, CK2, inhibitors, Membrane Matrix 2 Protein, M2, blockers and Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, inhibitors. The addition of adamantyl moiety seems to broaden and modify the therapeutic indices of the 4,5,6,7-tetrahalogeno-1H-benzimidazoles.<\/jats:p>","DOI":"10.3390\/molecules28010147","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T02:53:11Z","timestamp":1672109591000},"page":"147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis and Crystal Structure of Adamantylated 4,5,6,7-Tetrahalogeno-1H-benzimidazoles Novel Multi-Target Ligands (Potential CK2, M2 and SARS-CoV-2 Inhibitors); X-ray\/DFT\/QTAIM\/Hirshfeld Surfaces\/Molecular Docking Study"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9147-4484","authenticated-orcid":false,"given":"Jolanta Natalia","family":"Latosi\u0144ska","sequence":"first","affiliation":[{"name":"Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Pozna\u0144skiego 2, 61-614 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Latosi\u0144ska","sequence":"additional","affiliation":[{"name":"Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Pozna\u0144skiego 2, 61-614 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Orzeszko","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Warsaw University of Life Sciences, 159C Nowoursynowska St., 02-787 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Krzysztof","family":"Maurin","sequence":"additional","affiliation":[{"name":"National Medicines Institute, Che\u0142mska 30\/34, 00-750 Warsaw, Poland"},{"name":"National Centre for Nuclear Research, Andrzeja So\u0142tana 7, 05-400 Otwock-\u015awierk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.drudis.2006.11.008","article-title":"Multi-target therapeutics: When the whole is greater than the sum of the parts","volume":"12","author":"Zimmermann","year":"2007","journal-title":"Drug Discov. 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