{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:45:59Z","timestamp":1785422759332,"version":"3.56.0"},"reference-count":75,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["101184899"],"award-info":[{"award-number":["101184899"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["101184899"],"award-info":[{"award-number":["101184899"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This investigation focused on isoniazid (INH)\u2014saccharin (SAC) salts. One hydrate and one anhydrous INH-SAC salt form were synthesized and characterized spectroscopically by Raman and infrared spectroscopy. Solvent (methanol, acetone, acetonitrile)-assisted synthesis in the presence of water, or in water, resulted in production of the monohydrated form of the salt (MH: (INH+H)+\/(SAC\u2013H)\u2212.H2O). The anhydrous form (A: (INH+H)+\/(SAC\u2013H)\u2212) was obtained using the same synthesis method but in the absence of water or, together with the hydrate, in the presence of traces of water. Differential scanning calorimetry studies revealed that the hydrate can be converted into the anhydrous form of the salt upon heating, with the latter melting at a Tm (onset) of 131.7 \u00b1 0.5 \u00b0C. Melting was followed by a reaction between isoniazid and saccharin leading to saccharin ring opening and formation of a new covalent hydrazide\u2013amide derivative, via nucleophilic acyl substitution at the saccharin carbonyl. The newly formed adduct, 2-[2-(pyridine-4-carbonyl)hydrazine-1-carbonyl] benzene-1-sulfonamide, melts at Tm (onset) = 204.4 \u00b1 0.5 \u00b0C. The crystal structures of the hydrate and of the anhydrous form were determined by single-crystal X-ray diffraction, and the dominant intermolecular interactions in the crystalline INH-SAC salts were evaluated using Hirshfeld surface analysis. To complement the experimental results, density functional theory (DFT) calculations were performed both on relevant isolated structural units and on the two salts, employing fully periodic DFT methods.<\/jats:p>","DOI":"10.3390\/molecules31122187","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T08:19:52Z","timestamp":1782202792000},"page":"2187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Isoniazid\u2013Saccharin Salts: Synthesis, Structural Aspects, Thermal Properties and Spectroscopic Characterization"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6343-161X","authenticated-orcid":false,"given":"Rezvan","family":"Mohammadi","sequence":"first","affiliation":[{"name":"Spectroscopy@IKU, IKU-SPECTRA Molecular Sciences and Spectroscopy Applied Research Center, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"},{"name":"Department of Physics, Faculty of Sciences and Letters, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayberk","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Spectroscopy@IKU, IKU-SPECTRA Molecular Sciences and Spectroscopy Applied Research Center, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"},{"name":"Department of Physics, Science Faculty, Istanbul University, Vezneciler, Istanbul 34118, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-4236","authenticated-orcid":false,"given":"Nihal","family":"Sarier","sequence":"additional","affiliation":[{"name":"Spectroscopy@IKU, IKU-SPECTRA Molecular Sciences and Spectroscopy Applied Research Center, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"},{"name":"Department of Civil Engineering, Faculty of Engineering, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-7395","authenticated-orcid":false,"given":"Jos\u00e9 Ant\u00f3nio","family":"Paix\u00e3o","sequence":"additional","affiliation":[{"name":"CFisUC, Department of Physics, University of Coimbra, 3004-516 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-5050","authenticated-orcid":false,"given":"Gulce","family":"Ogruc Ildiz","sequence":"additional","affiliation":[{"name":"Spectroscopy@IKU, IKU-SPECTRA Molecular Sciences and Spectroscopy Applied Research Center, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"},{"name":"Department of Physics, Faculty of Sciences and Letters, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-6854","authenticated-orcid":false,"given":"Rui","family":"Fausto","sequence":"additional","affiliation":[{"name":"Spectroscopy@IKU, IKU-SPECTRA Molecular Sciences and Spectroscopy Applied Research Center, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"},{"name":"Department of Physics, Faculty of Sciences and Letters, Istanbul Kultur University, Atakoy Campus, Bakirkoy, Istanbul 34156, T\u00fcrkiye"},{"name":"CQC\u2013IMS, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14233\/ajomc.2022.AJOMC-P373","article-title":"Isoniazid: An Exploratory Review","volume":"7","author":"Saini","year":"2022","journal-title":"Asian J. Org. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e041022209552","DOI":"10.2174\/1871526522666221004152324","article-title":"Isoniazid Derivatives as Anti-tubercular Agents: From Structural Design to Clinical Investigations","volume":"23","author":"Rishanlang","year":"2023","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.52768\/3068-8035\/1002","article-title":"With a Word of Caution in Geriatric Population","volume":"1","author":"Bhat","year":"2025","journal-title":"Ann. Gerontol. Geriatr. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3390\/ph5070690","article-title":"Chemotherapeutic Interventions Against Tuberculosis","volume":"5","author":"Shakya","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.bmcl.2015.01.050","article-title":"A Novel Molecule with Notable Activity Against Multi-Drug Resistant Tuberculosis","volume":"25","author":"Nair","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Singh, R., Kumar, P., and Tahlan, K. (2020). Drugs Against Mycobacterium Tuberculosis, in Drug Discovery Targeting Drug-Resistant Bacteria, Academic Press. Chapter 6.","DOI":"10.1016\/B978-0-12-818480-6.00006-0"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5588\/ijtld.16.0716","article-title":"Isoniazid-Resistant Tuberculosis: A Cause for Concern?","volume":"21","author":"Stagg","year":"2017","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lu, Y., Wang, L., Duanmu, H., Chanyasulkit, C., Strong, A.J., and Zhang, H. (2017). Preventive Therapy Against Tuberculosis. Handbook of Global Tuberculosis Control, Springer.","DOI":"10.1007\/978-1-4939-6667-7"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1549","DOI":"10.1016\/S2214-109X(22)00408-9","article-title":"Isoniazid Prophylaxis: Highly Effective But Underutilised to Prevent Tuberculosis in People Living with HIV","volume":"10","author":"Vojnov","year":"2022","journal-title":"Lancet Glob. Health"},{"key":"ref_10","unstructured":"Walker, A., Agarwal, A., and Jain, Y. (2023). Isoniazid for Preventing TB in HIV-Positive People in Infectious Diseases and Neglected Tropical Diseases, Oxford University Press. Chapter 23."},{"key":"ref_11","first-page":"41","article-title":"Inhibition by Isoniazid of Synthesis of Mycolic Acids in Mycobacterium tuberculosis","volume":"63","author":"Winder","year":"1970","journal-title":"Microbiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"197","DOI":"10.2174\/1389201023378328","article-title":"Drugs that Inhibit Mycolic Acid Biosynthesis in Mycobacterium tuberculosis","volume":"3","author":"Schroeder","year":"2002","journal-title":"Curr. Pharm. Biotech."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vilch\u00e8ze, C. (2020). Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs. Appl. Sci., 10.","DOI":"10.3390\/app10072278"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0041-3879(53)80038-3","article-title":"Isoniazid in the Treatment of Pulmonary Tuberculosis","volume":"34","author":"Collins","year":"1953","journal-title":"Tubercle"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.58395\/pipd.v50i1.83","article-title":"Current Approaches to Control of Isoniazid-Resistant Tuberculosis","volume":"50","author":"Milanov","year":"2022","journal-title":"Probl. Infect. Parasit. Dis."},{"key":"ref_16","first-page":"4606","article-title":"Management of Isoniazid Monoresistant Tuberculosis","volume":"8","author":"Yandhi","year":"2024","journal-title":"Biosci. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1080\/10837450500299982","article-title":"Drug-Drug Interaction Studies on First-Line Anti Tuberculosis Drugs","volume":"10","author":"Bhutani","year":"2005","journal-title":"Pharm. Dev. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/j.2055-2335.2005.tb00333.x","article-title":"Extemporaneous Isoniazid Mixture: Stability Implications","volume":"35","author":"Haywood","year":"2005","journal-title":"J. Pharm. Pract. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.jpba.2005.05.015","article-title":"Mechanistic Explanation to the Catalysis by Pyrazinamide and Ethambutol of Reaction Between Rifampicin and Isoniazid in Anti-TB FDCs","volume":"39","author":"Bhutani","year":"2005","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1081\/DDC-120021772","article-title":"Behavior of Decomposition of Rifampicin in the Presence of Isoniazid in the pH Range 1\u20133","volume":"29","author":"Sankar","year":"2003","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1081\/DDC-120039184","article-title":"An Explanation for the Physical Instability of a Marketed Fixed Dose Combination (FDC) Formulation Containing Isoniazid and Ethambutol and Proposed Solutions","volume":"30","author":"Bhutani","year":"2004","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"129388","DOI":"10.1016\/j.molstruc.2020.129388","article-title":"Isoniazid-Gentisic Acid Cocrystallization: Solubility, Stability, Dissolution Rate, Antioxidant and Flowability Properties Studies","volume":"1226","author":"Mashhadi","year":"2021","journal-title":"J. Mol. Struct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121924","DOI":"10.1016\/j.ijpharm.2022.121924","article-title":"Cocrystals of Tuberculosis Antibiotics: Challenges and Missed Opportunities","volume":"623","author":"Salem","year":"2022","journal-title":"Int. J. Pharm. Sci."},{"key":"ref_24","unstructured":"Inan, N.I., Syeitkhajy, A., Yilmaz, A., Sarier, N., Ildiz, G.O., and Fausto, R. (Photochem. Spectrosc., 2026). Synthesis, Structure, Vibrational Spectra and Thermal Analysis of Isoniazid-Succinic Acid Cocrystal, Photochem. Spectrosc., in press."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.12775\/JEHS.2020.10.04.011","article-title":"What Do We Know About Sugar Substitutes","volume":"10","author":"Majewski","year":"2020","journal-title":"J. Educ. Health Sport"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6","DOI":"10.29328\/journal.niogb.1001021","article-title":"Navigating Weight Management with Stevia: Insights into Glycemic Control","volume":"8","author":"Kharat","year":"2024","journal-title":"New Insights Obes. Gene. Beyond."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Begum, R.F., Nirenjen, S., Rushendran, R., Manisha, M., Pavithra, N., Sridevi, S., and Singh, S.A. (2025). Exploring the Impact of Artificial Sweeteners on Diabetes Management and Glycemic Control. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1587690"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.22159\/ijap.2024v16i1.48829","article-title":"Preparation and Solid-State Characterization of Ketoprofen-Succinic Acid-Saccharin Cocrystal with Improved Solubility","volume":"16","author":"Imanto","year":"2024","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3897\/pharmacia.70.e98177","article-title":"Carvedilol Solubility Enhancement by Multicomponent Crystallization with Coformers of Benzoic Acid, Isonicotinamide, and Saccharin","volume":"70","author":"Sopyan","year":"2023","journal-title":"Pharmacia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1006\/rtph.2002.1542","article-title":"Aspartame: Review of Safety","volume":"35","author":"Butchko","year":"2002","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_31","first-page":"225","article-title":"Artificial Sweeteners: Safe or Unsafe?","volume":"65","author":"Khan","year":"2015","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.56501\/intjcommunitydent.v10i1.41","article-title":"Artificial Sweeteners: A Review","volume":"10","author":"Patel","year":"2022","journal-title":"Int. J. Community Dent."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"102356","DOI":"10.1016\/j.rechem.2025.102356","article-title":"Environmental and Health Impacts of Selected Artificial Sweeteners: Effectiveness of Treatment Methods and Innovative Approaches for Mitigation","volume":"16","author":"Sawma","year":"2025","journal-title":"Results Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Syeitkhajy, A., Yilmaz, A., Sarier, N., Ildiz, G.O., and Fausto, R. (J. Mol. Struct., 2026). Picolinamide-Saccharin Cocrystal: Synthesis, Structure, Vibrational Spectra and Thermal Behavior, J. Mol. Struct., preprint.","DOI":"10.2139\/ssrn.6512211"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/BF00549096","article-title":"Bonded-Atom Fragments for Describing Molecular Charge Densities","volume":"44","author":"Hirshfeld","year":"1977","journal-title":"Theor. Chim. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0009-2614(97)00100-0","article-title":"A Novel Definition of a Molecule in a Crystal","volume":"267","author":"Spackman","year":"1977","journal-title":"Chem. Phys. Lett."},{"key":"ref_37","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 Cryst. B"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1039\/B818330A","article-title":"Hirshfeld Surface Analysis","volume":"11","author":"Spackman","year":"2009","journal-title":"CrystEngComm"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1039\/b704980c","article-title":"Towards Quantitative Analysis of Intermolecular Interactions with Hirshfeld Surfaces","volume":"7","author":"McKinnon","year":"2007","journal-title":"Chem. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1039\/B203191B","article-title":"Fingerprinting Intermolecular Interactions in Molecular Crystals","volume":"4","author":"Spackman","year":"2002","journal-title":"CrystEngComm"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.molstruc.2006.12.056","article-title":"Vibrational structure of Free and Hydrogen Bonded Complexes of Isoniazid: FT-IR, FT-Raman and DFT Study","volume":"834\u2013836","author":"Akalin","year":"2007","journal-title":"J. Mol. Struct."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9220","DOI":"10.1021\/jp9037914","article-title":"Molecular Structure, Infrared Spectra, and Photochemistry of Isoniazid under Cryogenic Conditions","volume":"113","author":"Borba","year":"2009","journal-title":"J. Phys. Chem. A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1039\/c000473a","article-title":"One-pot Covalent and Supramolecular Synthesis of Pharmaceutical Co-Crystals Using the API Isoniazid: A Potential Supramolecular Reagent","volume":"12","author":"Lemmerer","year":"2010","journal-title":"CrystEngComm"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1039\/C1CE06310C","article-title":"Covalent Assistance to Supramolecular Synthesis: Modifying the Drug Functionality of the Antituberculosis API Isoniazid in situ During Co-Crystallization with GRAS and API Compounds","volume":"14","author":"Lemmerer","year":"2012","journal-title":"CrystEngComm"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"o1944","DOI":"10.1107\/S1600536805016600","article-title":"Saccharin, Redetermined at 120 K: A Three-Dimensional Hydrogen-Bonded Framework","volume":"E61","author":"Wardell","year":"2005","journal-title":"Acta Cryst. E"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1080\/14786440109462720","article-title":"On Lines and Planes of Closest Fit to Systems of Points in Space","volume":"2","author":"Pearson","year":"1901","journal-title":"Phil. Mag."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1037\/h0071325","article-title":"Analysis of a Complex of Statistical Variables into Principal Components","volume":"24","author":"Hotelling","year":"1933","journal-title":"J. Educ. Psychol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1037\/h0070888","article-title":"Analysis of a Complex of Statistical Variables into Principal Components","volume":"24","author":"Hotelling","year":"1933","journal-title":"J. Educ. Psychol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/biomet\/28.3-4.321","article-title":"Relations Between Two Sets of Variates","volume":"28","author":"Hotelling","year":"1936","journal-title":"Biometrika"},{"key":"ref_50","unstructured":"El-Baz, A.S., and Mahmoud, A. (2021). Blood Serum Infrared Spectra Based Chemometric Models for Auxiliary Diagnosis of Autism Spectrum Disorder. Neural Engineer Techniques for Autism Spectrum Disorder, Elsevier Science. Chapter 10."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"(OriginPro, 2021). OriginPro, Version 2021 (64-bit), 9.8.0.200.","DOI":"10.25291\/VR\/64-VR-200"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ngilirabanga, J.B., Aucamp, M., Pires Rosa, P., and Samsodien, H. (2020). Mechanochemical Synthesis and Physicochemical Characterization of Isoniazid and Pyrazinamide Co-crystals with Glutaric Acid. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.595908"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1080\/10408347.2017.1281098","article-title":"Isoniazid: A Review of Characteristics, Properties and Analytical Methods","volume":"47","author":"Fernandes","year":"2017","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10973-009-0084-6","article-title":"Thermal Studies of Isoniazid and Mixtures with Rifampicin","volume":"97","author":"Freire","year":"2009","journal-title":"J. Therm. Anal. Calorim."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/00268970512331316175","article-title":"Saccharin: A Combined Experimental and Computational Thermochemical Investigation of a Sweetener and Sulfonamide","volume":"103","author":"Matos","year":"2005","journal-title":"Mol. Phys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1007\/s11095-007-9394-1","article-title":"Indomethacin-Saccharin Cocrystal: Design, Synthesis and Preliminary Pharmaceutical Characterization","volume":"25","author":"Basavoju","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_57","first-page":"4652\u22124667","article-title":"Uncovering Cocrystal Formation and Competition Mechanism of Polyhydroxy Natural Products: Cases of Quercetin, Hesperidin, Resveratrol, and Curcumin","volume":"24","author":"Li","year":"2024","journal-title":"Cryst. Growth Des."},{"key":"ref_58","unstructured":"(2023). APEX6: Software Suite for Crystallographic Data Collection and Reduction, Bruker AXS Inc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053273314026370","article-title":"SHELXT-Integrated Space-Group and Crystal-Structure Determination","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Cryst. A Found. Crystallogr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal Structure Refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Cryst. C Cryst. Struct. Commun."},{"key":"ref_61","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_62","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1107\/S1600576719014092","article-title":"Mercury 4.0: From Visualization to Analysis, Design and Prediction","volume":"53","author":"Macrae","year":"2020","journal-title":"J. Appl. Crystallogr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1107\/S1600576715014685","article-title":"Profex: A Graphical User Interface for the Rietveld Refinement Program BGMN","volume":"48","author":"Kleeberg","year":"2015","journal-title":"J. Appl. Crystallogr."},{"key":"ref_64","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., and Nakatsuji, H. (Gaussian 16, 2016). Gaussian 16, Revision A.03."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","article-title":"Development of the Colle\u2013Salvetti Correlation-Energy Formula into a Functional of the Electron Density","volume":"37","author":"Lee","year":"1988","journal-title":"Phys. Rev. B"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1103\/PhysRevA.38.3098","article-title":"Density-Functional Exchange-Energy Approximation with Correct Asymptotic Behavior","volume":"38","author":"Becke","year":"1988","journal-title":"Phys. Rev. A"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1063\/1.464913","article-title":"Density-Functional Thermochemistry. III. The Role of Exact Exchange","volume":"98","author":"Becke","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5639","DOI":"10.1063\/1.438980","article-title":"Contracted Gaussian Basis Sets for Molecular Calculations. I. Second-Row Atoms, Z = 11\u201318","volume":"72","author":"McLean","year":"1980","journal-title":"J. Chem. Phys."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1063\/1.438955","article-title":"Self-Consistent Molecular Orbital Methods. XX. A Basis Set for Correlated Wave Functions","volume":"72","author":"Krishnan","year":"1980","journal-title":"J. Chem. Phys."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1021\/ja00523a008","article-title":"Self-Consistent Molecular Orbital Methods. XXI. Small Split-Valence Basis Sets for First-Row and Second-Row Atoms","volume":"102","author":"Binkley","year":"1980","journal-title":"J. Am. Chem. Soc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1360","DOI":"10.1002\/wcms.1360","article-title":"Quantum-Mechanical Condensed Matter Simulations with CRYSTAL17","volume":"8","author":"Dovesi","year":"2018","journal-title":"WIREs Comput. Mol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1063\/1.1677527","article-title":"Self-Consistent Molecular Orbital Methods. XII. Further Extensions of Gaussian-Type Basis Sets for Use in Molecular Orbital Studies of Organic Molecules","volume":"56","author":"Hehre","year":"1972","journal-title":"J. Chem. Phys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF00533485","article-title":"The Influence of Polarization Functions on Molecular Orbital Hydrogenation Energies","volume":"28","author":"Hariharan","year":"1973","journal-title":"Theor. Chim. Acta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1002\/jcc.21759","article-title":"Effect of the Damping Function in Dispersion-Corrected Density Functional Theory","volume":"32","author":"Grimme","year":"2011","journal-title":"J. Comput. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1107\/S1600576721002910","article-title":"CrystalExplorer: A program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals","volume":"54","author":"Spackman","year":"2021","journal-title":"Appl. Cryst."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/12\/2187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:42:11Z","timestamp":1782535331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/12\/2187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":75,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["molecules31122187"],"URL":"https:\/\/doi.org\/10.3390\/molecules31122187","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]}}}