{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T18:56:07Z","timestamp":1774292167220,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre in Poland","award":["UMO-2017\/25\/B\/NZ3\/00251"],"award-info":[{"award-number":["UMO-2017\/25\/B\/NZ3\/00251"]}]},{"name":"National Science Centre in Poland","award":["UMO-2017\/24\/C\/NZ1\/00366"],"award-info":[{"award-number":["UMO-2017\/24\/C\/NZ1\/00366"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The results of structural studies on a series of halogen-substituted derivatives of 2-deoxy-D-glucose (2-DG) are reported. 2-DG is an inhibitor of glycolysis, a metabolic pathway crucial for cancer cell proliferation and viral replication in host cells, and interferes with D-glucose and D-mannose metabolism. Thus, 2-DG and its derivatives are considered as potential anticancer and antiviral drugs. X-ray crystallography shows that a halogen atom present at the C2 position in the pyranose ring does not significantly affect its conformation. However, it has a noticeable effect on the crystal structure. Fluorine derivatives exist as a dense 3D framework isostructural with the parent compound, while Cl- and I-derivatives form layered structures. Analysis of the Hirshfeld surface shows formation of hydrogen bonds involving the halogen, yet no indication for the existence of halogen bonds. Density functional theory (DFT) periodic calculations of cohesive and interaction energies (at the B3LYP level of theory) have supported these findings. NMR studies in the solution show that most of the compounds do not display significant differences in their anomeric equilibria, and that pyranose ring puckering is similar to the crystalline state. For 2-deoxy-2-fluoro-D-glucose (2-FG), electrostatic interaction energies between the ligand and protein for several existing structures of pyranose 2-oxidase were also computed. These interactions mostly involve acidic residues of the protein; single amino-acid substitutions have only a minor impact on binding. These studies provide a better understanding of the structural chemistry of halogen-substituted carbohydrates as well as their intermolecular interactions with proteins determining their distinct biological activity.<\/jats:p>","DOI":"10.3390\/ijms22073720","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T10:34:09Z","timestamp":1617359649000},"page":"3720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Experimental and Computational Studies on Structure and Energetic Properties of Halogen Derivatives of 2-Deoxy-D-Glucose"],"prefix":"10.3390","volume":"22","author":[{"given":"Marcin","family":"Ziemniak","sequence":"first","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-7923","authenticated-orcid":false,"given":"Anna","family":"Zawadzka-Kazimierczuk","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Pawl\u0119dzio","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-7041","authenticated-orcid":false,"given":"Maura","family":"Malinska","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"So\u0142tyka","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetics and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian","family":"Trzybi\u0144ski","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2319-4525","authenticated-orcid":false,"given":"Wiktor","family":"Ko\u017ami\u0144ski","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanis\u0142aw","family":"Skora","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafa\u0142","family":"Zieli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabela","family":"Fokt","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldemar","family":"Priebe","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0277-294X","authenticated-orcid":false,"given":"Krzysztof","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-8860","authenticated-orcid":false,"given":"Beata","family":"Paj\u0105k","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetics and Molecular Biology, Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pajak, B., Siwiak, E., So\u0142tyka, M., Priebe, A., Zieli\u0144ski, I.R., Fokt, I., Ziemniak, M., Ja\u015bkiewicz, A., Borowski, R., and Domoradzki, T. (2019). 2-Deoxy-D-glucose and its analogs: From diagnostic to therapeutic agents. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010234"},{"key":"ref_2","unstructured":"Phelps, M.E. (2004). PET: Molecular Imaging and its Biological Applications, Springer."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1053\/j.seminoncol.2019.07.001","article-title":"PET\/CT in radiation oncology","volume":"46","author":"Fonti","year":"2019","journal-title":"Semin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1016\/j.tet.2010.03.001","article-title":"Preparation and reactions of iodo sugars","volume":"66","author":"Marzabadi","year":"2010","journal-title":"Tetrahedron"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1016\/j.carres.2009.06.016","article-title":"D-Glucose and D-mannose-based antimetabolites. Part 2. Facile synthesis of 2-deoxy-2-halo-D-glucoses and -D-mannoses","volume":"344","author":"Fokt","year":"2009","journal-title":"Carbohydr. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s00280-006-0207-8","article-title":"Efficacy of 2-halogen substituted D-glucose analogs in blocking glycolysis and killing \u201chypoxic tumor cells\u201d","volume":"58","author":"Lampidis","year":"2006","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_7","first-page":"460","article-title":"Cancer metabolism as a therapeutic target","volume":"27","author":"Batra","year":"2013","journal-title":"Oncology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"166016","DOI":"10.1016\/j.bbadis.2020.166016","article-title":"Cancer cell metabolism: Rewiring the mitochondrial hub","volume":"1867","author":"Oliveira","year":"2021","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114213","DOI":"10.1016\/j.bcp.2020.114213","article-title":"Cellular toxicity of the metabolic inhibitor 2-deoxyglucose and associated resistance mechanisms","volume":"182","author":"Laussel","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/1476-4598-8-122","article-title":"2-deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated upregulation of TRAIL-R2","volume":"8","author":"Liu","year":"2009","journal-title":"Mol. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s10585-011-9417-5","article-title":"Glycolysis inhibition by 2-deoxy-D-glucose reverts the metastatic phenotype in vitro and in vivo","volume":"28","author":"Sottnik","year":"2011","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.mehy.2007.08.021","article-title":"2-deoxy-D-glucose as a potential drug against fusogenic viruses including HIV","volume":"70","author":"Parris","year":"2008","journal-title":"Med. Hypotheses"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41586-020-2332-7","article-title":"Proteomics of SARS-CoV-2-infected host cells reveals therapy targets","volume":"583","author":"Bojkova","year":"2020","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Balkrishna, A., Thakur, P., Singh, S., Dev, S., Jain, V., Varshney, A., and Sharma, R. (2021). Computional screening approaches for investigating potential activity of phytoligands against SARS-CoV-2. Res. Square.","DOI":"10.36069\/JoLS\/20210302"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Niccoli, S., Boreham, D.R., Phenix, C.P., and Lees, S.J. (2017). Non-radioactive 2-deoxy-2-fluoro-D-glucose inhibits glucose uptake in xenograft tumours and sensitizes HeLa cells to doxorubicin in vitro. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187584"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1167\/iovs.11-8265","article-title":"Retinoblastoma treatment: Utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-D-glucose (2-FG), to target the chemoresistant hypoxic regions in LH9BETA)T(AG) retinal tumors","volume":"53","author":"Decatur","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"o496","DOI":"10.1107\/S0108270110034001","article-title":"Co-crystals of 3-deoxy-3-fluoro-\u03b1-D-glucopyranose and 3-deoxy-\u03b2-D-glucopyranose","volume":"66","author":"Zhang","year":"2010","journal-title":"Acta Crystallogr. C Cryst. Struct. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4721","DOI":"10.1038\/s41467-018-06901-y","article-title":"A Chiron approach towards the stereoselective synthesis of polyfluorinated carbohydrates","volume":"9","author":"Denavit","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.carres.2011.04.007","article-title":"The conformation of tetrafluorinated methyl galactoside anomers: Crystallographic and NMR studies","volume":"346","author":"Linclau","year":"2011","journal-title":"Carbohydrate Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13499","DOI":"10.1002\/chem.202002825","article-title":"Addressing the structural complexity of fluorinated glucose analogues: Insight into lipophilicities and solvation effects","volume":"26","author":"Johnson","year":"2020","journal-title":"Chem. Eur. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.addr.2003.10.010","article-title":"Polymorphism in generic drug product development","volume":"56","author":"Snider","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18759","DOI":"10.3390\/molecules201018759","article-title":"Polymorph impact on the bioavailability and stability of poorly soluble drugs","volume":"20","author":"Censi","year":"2015","journal-title":"Molecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1039\/C4CC09074H","article-title":"Energy frameworks: Insights into interaction anisotropy and the mechanical properties of molecular crystals","volume":"51","author":"Turner","year":"2015","journal-title":"Chem. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1021\/cr990112c","article-title":"Chemical applications of the X-ray charge-density analysis","volume":"101","author":"Koritsanszky","year":"2001","journal-title":"Chem. Rev."},{"key":"ref_25","first-page":"1150","article-title":"Crystal structure, interaction energies and experimental electron density of the popular drug ketoprofen","volume":"1","author":"Makal","year":"2018","journal-title":"IUCrJ"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13065-014-0068-x","article-title":"Charge density analysis for crystal engineering","volume":"8","author":"Krawczuk","year":"2014","journal-title":"Chem. Cent. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/0889311X.2013.785538","article-title":"Modern charge density studies: The entanglement of experimental and theory","volume":"19","author":"Macchi","year":"2013","journal-title":"Crystallogr. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.1039\/D0CE00525H","article-title":"Influence of halogen size on the supramolecular and energy landscape of the THF solvates of the halogen derivatives of dianthranilide","volume":"22","author":"Bieszczad","year":"2020","journal-title":"CrystEngComm"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1021\/ja00839a011","article-title":"A general definition of ring puckering coordinates","volume":"97","author":"Cremer","year":"1975","journal-title":"J. Am. Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0008-6215(00)80666-7","article-title":"The crystal structure of 2-deoxy-D-arabino-hexopyranose at -150\u00b0","volume":"97","author":"Maluszynska","year":"1981","journal-title":"Carbohydrate Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1039\/B711844A","article-title":"Understanding organofluorine chemistry. An introduction to the C-F bond","volume":"37","year":"2008","journal-title":"Chem. Soc. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5822","DOI":"10.1021\/acs.jmedchem.7b01788","article-title":"Fluorine and fluorinated motifs in the design and application of bioisosteres for drug design","volume":"61","author":"Meanwell","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"o2615","DOI":"10.1107\/S1600536811035264","article-title":"2-deoxy-D-arabino-hexopyranose","volume":"67","author":"Hess","year":"2011","journal-title":"Acta Crystallogr. Sect. E Struct. Rep. Online"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.carres.2013.02.005","article-title":"Perspective on the primary and three-dimensional structures of carbohydrates","volume":"378","author":"Widmalm","year":"2013","journal-title":"Carbohydr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kirby, A.J. (1983). The Anomeric Effect and Related Stereoelectronic Effects at Oxygen, Springer.","DOI":"10.1007\/978-3-642-68676-4"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Miljkovic, M. (2009). Carbohydrates, Springer.","DOI":"10.1007\/978-0-387-92265-2"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1021\/ja00081a037","article-title":"The origin of the anomeric effect: Conformational analysis of 2-methoxy-1,3-dimethylhexahydropyrimidine","volume":"116","author":"Perrin","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1021\/ja01160a021","article-title":"The shape of pyranoside rings","volume":"72","author":"Reeves","year":"1950","journal-title":"J. Am. Chem. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1021\/jo01021a030","article-title":"Conformational and configurational studies on some acetylated aldopyranosyl halides","volume":"30","author":"Horton","year":"1965","journal-title":"J. Org. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/mrc.1260270608","article-title":"Relationship between proton-proton NMP coupling constants and subsituent electronegativities. IV\u2014An extended Karplus equation accounting for interactions between substituents and its application to coupling constant data calculated by the Extended Huckel method","volume":"27","author":"Donders","year":"1989","journal-title":"Magn. Reson. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1107\/S2052252515011239","article-title":"Sub-atomic resolution X-ray crystallography and neutron crystallography: Promise, challenges and potential","volume":"2","author":"Blakeley","year":"2015","journal-title":"IUCrJ"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1021\/jo010985i","article-title":"Hydroxymethyl group conformation in saccharides: Structural dependencies of 2JHH, 3JHH, and 1JCH spin-spin coupling constants","volume":"67","author":"Stenutz","year":"2002","journal-title":"J. Org. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1021\/cr000115l","article-title":"Oxidative mechanisms involved in lignin degradation by white-rot fungi","volume":"101","author":"Teunissen","year":"2001","journal-title":"Chem. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1128\/AEM.67.8.3636-3644.2001","article-title":"Purification and characterization of pyranose oxidase from white rot fungus Trametes multicolor","volume":"67","author":"Leitner","year":"2001","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35104","DOI":"10.1074\/jbc.M604718200","article-title":"Structural basis for substrate binding and regioselective oxidation of monosac-charides at C3 by pyranose 2-oxidase","volume":"281","author":"Kujawa","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1111\/j.1742-4658.2010.07705.x","article-title":"Importance of the gating segment in the substrate-recognition loop of pyranose 2-oxidase","volume":"277","author":"Spadiut","year":"2010","journal-title":"FEBS J."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tan, T.C., Spadiut, O., Gandini, R., Haltrich, D., and Divne, C. (2014). Structural basis for binding of fluorinated glucose and galactose to Trametes multicolor pyranose 2-oxidase variants with improved galactose conversion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086736"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1107\/S0108767395007367","article-title":"The analytical calculation of absorption in multifaceted crystals","volume":"51","author":"Clark","year":"1995","journal-title":"Acta Crystallogr. A"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"Crystal structure refinement with SHELXL","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr. A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1107\/S090744490804362X","article-title":"Structure validation in chemical crystallography","volume":"65","author":"Spek","year":"2009","journal-title":"Acta Crystallogr. D Biol Crystallogr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1107\/S0021889808042726","article-title":"OLEX2: A complete structure solution, refinement and analysis program","volume":"42","author":"Dolomanov","year":"2009","journal-title":"J. Appl. Crystallogr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1107\/S0021889807067908","article-title":"New features for the visualization and investigation of crystal structures","volume":"41","author":"Macrae","year":"2008","journal-title":"J. Appl. Crystallogr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/qua.24658","article-title":"CRYSTAL14: A program for the ab initio investigation of crystalline solids","volume":"114","author":"Dovesi","year":"2014","journal-title":"Int. J. Quantum Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/jcc.10205","article-title":"Chemical information from the source function","volume":"24","author":"Gatti","year":"2003","journal-title":"J. Comput. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/jcc.23153","article-title":"Consistent gaussian basis sets of Triple-Zeta valence with polarization quality for solid-state calculations","volume":"34","author":"Peintinger","year":"2013","journal-title":"J. Comput. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1002\/jcc.25195","article-title":"Consistent gaussian basis sets of double- and triple-zeta valence with polarization quality of the fifth period for solid-state calculations","volume":"39","author":"Laun","year":"2018","journal-title":"J. Comput. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1002\/jcc.20078","article-title":"Accurate description of van der Waals complexes by density functional theory including empirical corrections","volume":"25","author":"Grimme","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1002\/jcc.20495","article-title":"Semiempirical GGA-type density functional constructed with a long-range dispersion correction","volume":"27","author":"Grimme","year":"2006","journal-title":"J. Comput. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1080\/00268977000101561","article-title":"The calculation of small molecular interactions by the differences of separate total energies","volume":"19","author":"Boys","year":"1970","journal-title":"Mol. Phys."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1039\/B818330A","article-title":"Hishfeld surface analysis","volume":"11","author":"Spackman","year":"2009","journal-title":"Cryst. Eng. Comm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1107\/S0108768104020300","article-title":"Novel tools for visualizing and exploring intermolecular interactions in molecular crystals","volume":"60","author":"McKinnon","year":"2004","journal-title":"Acta Crystallogr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1107\/S2052252514003327","article-title":"The enrichment ration of atomic contacts in crystals, an indicator derived the Hirshfeld surface analysis","volume":"1","author":"Jelsch","year":"2014","journal-title":"IUCrJ"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1107\/S0108767311042176","article-title":"New version of the theoretical databank of transferable aspherical pseudoatoms, UBDB2011\u2014Towards nucleic acid modelling","volume":"68","author":"Jarzembska","year":"2012","journal-title":"Acta Crystallogr. Sect. A"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.cplett.2004.04.097","article-title":"Combination of the exact potential and multipole methods (EP\/MM) for evaluation of intermolecular electrostatic interaction energies with pseudoatom representation of molecular electron densities","volume":"391","author":"Volkov","year":"2004","journal-title":"Chem. Phys. Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1107\/S0567739478001886","article-title":"Testing aspherical atom refinements on small-molecule data sets","volume":"34","author":"Hansen","year":"1978","journal-title":"Acta Crystallogr. Sect. A"},{"key":"ref_67","unstructured":"Volkov, A., Macchi, P., Farrugia, L.J., Gatti, C., Mallinson, P., Richter, T., and Koritsanszky, T. (2006). XD2016\u2014A Computer Program Package for Multipole Refinement, Topological Analysis of Charge Densities and Evaluation of Intermolecular Energies from Experimental and Theoretical Structure Factors, University at Buffalo\u2014The State University of New York."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/pro.3235","article-title":"UCSF ChimeraX: Meeting modern challenges in visualization and analysis","volume":"27","author":"Goddard","year":"2018","journal-title":"Protein Sci."},{"key":"ref_69","unstructured":"Goddard, T.D., and Kneller, D.G. (2008). SPARKY 3, University of California."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/mrc.1260321107","article-title":"Empirical group electronegativities for vicinal NMR proton\u2014Proton couplings along a C-C bond: Solvent effects and reparameterization of the Haasnoot equation","volume":"32","author":"Altona","year":"1994","journal-title":"Magn. Reson. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/mrc.1260270609","article-title":"Relationship between proton-proton NMR coupling constants and substituent electronegativities. V\u2020\u2014Empirical substituent constants deduced from ethanes and propane","volume":"27","author":"Altona","year":"1989","journal-title":"Magn. Reson. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3720\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:11:07Z","timestamp":1760364667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/7\/3720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,2]]},"references-count":72,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22073720"],"URL":"https:\/\/doi.org\/10.3390\/ijms22073720","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,2]]}}}