{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:12:25Z","timestamp":1789564345390,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"EU FP7 Marie Curie grant","doi-asserted-by":"publisher","award":["PCIG12-GA-2012-334525"],"award-info":[{"award-number":["PCIG12-GA-2012-334525"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"King\u2019s College London","award":["PCIG12-GA-2012-334525"],"award-info":[{"award-number":["PCIG12-GA-2012-334525"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Benzenesulfonamides are a class of molecules of extreme interest in the biochemical field because many of them are active against a variety of diseases. In this work, the pharmacophoric group benzensulfonamide, its derivatives para-toluensulfonamide and ortho-toluensulfonamide, and the bioactive molecule sulfanilamide, were investigated using rotational spectroscopy to determine their conformations and the influence of different substituents on their structures. For all species, the hyperfine structure due to the 14N atom was analyzed, and this provided crucial information for the unambiguous identification of the observed conformation of all molecules. In addition, for ortho-toluensulfonamide, the vibration\u2013rotation hyperfine structure related to the methyl torsion was analyzed, and the methyl group rotation barrier was determined. For benzensulfonamide, partial rS and r0 structures were established from the experimental rotational constants of the parent and two deuterated isotopic species. In all compounds except ortho-toluensulfonamide, the amino group of the sulfonamide group lies perpendicular to the benzene plane with the aminic hydrogens eclipsing the oxygen atoms. In ortho-toluensulfonamide, where weak attractive interactions occur between the nitrogen lone pair and the methyl hydrogen atoms, the amino group lies in a gauche orientation, retaining the eclipsed configuration with respect to the SO2 frame. A comparison of the geometrical arrangements found in the PDB database allowed us to understand that the bioactive conformations are different from those found in isolated conditions. The conformations within the receptor are reached with an energy cost, which is balanced by the interactions established in the receptor.<\/jats:p>","DOI":"10.3390\/molecules27092820","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T22:20:06Z","timestamp":1651184406000},"page":"2820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Shapes of Sulfonamides: A Rotational Spectroscopy Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Annalisa","family":"Vigorito","sequence":"first","affiliation":[{"name":"Dipartimento di Chimica \u201cG. Ciamician\u201d dell\u2019Universit\u00e0, via Selmi 2, I-40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-2098","authenticated-orcid":false,"given":"Camilla","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cG. Ciamician\u201d dell\u2019Universit\u00e0, via Selmi 2, I-40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2644-0023","authenticated-orcid":false,"given":"Assimo","family":"Maris","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cG. Ciamician\u201d dell\u2019Universit\u00e0, via Selmi 2, I-40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-8010","authenticated-orcid":false,"given":"Donatella","family":"Loru","sequence":"additional","affiliation":[{"name":"Department of Chemistry, King\u2019s College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Chemistry, King\u2019s College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Eugenia","family":"Sanz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, King\u2019s College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0410-5833","authenticated-orcid":false,"given":"Sonia","family":"Melandri","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica \u201cG. Ciamician\u201d dell\u2019Universit\u00e0, via Selmi 2, I-40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"ref_1","unstructured":"(2022, April 09). Available online: www.c4xdiscovery.com."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/bs.pmch.2015.10.003","article-title":"Measurement, Interpretation and Use of Free Ligand Solution Conformations in Drug Discovery","volume":"55","author":"Blundell","year":"2016","journal-title":"Prog. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nsb0697-490","article-title":"Crystal Structure of the Anti-Bacterial Sulfonamide Drug Target Dihydropteroate Synthase","volume":"4","author":"Achari","year":"1997","journal-title":"Nat. Struct. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1021\/cr050262p","article-title":"Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein\u2212Ligand Binding","volume":"108","author":"Krishnamurthy","year":"2008","journal-title":"Chem. Rev."},{"key":"ref_5","first-page":"3327","article-title":"Carbonic Anhydrase Inhibitors. Inhibition of the Zinc and Cobalt \u03b3-Class Enzyme from the Archaeon Methanosarcina Thermophila with Anions","volume":"14","author":"Innocenti","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4236\/jbnb.2011.22018","article-title":"Al Synthesis, Structure Analysis and Antibacterial Activity of New Potent Sulfonamide Derivatives","volume":"02","author":"Alsughayer","year":"2011","journal-title":"J. Biomater. Nanobiotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"925","DOI":"10.2174\/0929867033457647","article-title":"Anticancer and Antiviral Sulfonamides","volume":"10","author":"Scozzafava","year":"2003","journal-title":"Curr. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1021\/jm030912m","article-title":"Unexpected Nanomolar Inhibition of Carbonic Anhydrase by COX-2-Selective Celecoxib: New Pharmacological Opportunities Due to Related Binding Site Recognition","volume":"47","author":"Weber","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1080\/00268979100102661","article-title":"Microwave Spectrum and Ab Initio Calculations of Ethylbenzene: Potential Energy Surface of the Ethyl Group Torsion","volume":"74","author":"Caminati","year":"1991","journal-title":"Mol. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0022-2860(86)80166-1","article-title":"Microwave Spectrum of Anisole","volume":"144","author":"Onda","year":"1986","journal-title":"J. Mol. Struct."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/1439-7641(20010316)2:3<172::AID-CPHC172>3.0.CO;2-V","article-title":"Intramolecular Hydrogen Bonds and Conformational Properties of Benzylamine","volume":"2","author":"Melandri","year":"2001","journal-title":"ChemPhysChem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6913","DOI":"10.1021\/jp102903p","article-title":"Rotational Spectrum, Tunneling Motions, and Potential Barriers of Benzyl Alcohol","volume":"114","author":"Utzat","year":"2010","journal-title":"J. Phys. Chem. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1021\/jp076969s","article-title":"Multitechnique Investigation of Conformational Features of Small Molecules: The Case of Methyl Phenyl Sulfoxide","volume":"112","author":"Celebre","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/cphc.201500234","article-title":"Detection of Significant Aprotic Solvent Effects on the Conformational Distribution of Methyl 4-Nitrophenyl Sulfoxide: From Gas-Phase Rotational to Liquid-Crystal NMR Spectroscopy","volume":"16","author":"Celebre","year":"2015","journal-title":"ChemPhysChem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/0009-2614(95)00810-Q","article-title":"Free Jet Absorption Millimeter Wave Spectrum of Benzene Sulphonyl Chloride","volume":"243","author":"Caminati","year":"1995","journal-title":"Chem. Phys. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1021\/jo0524270","article-title":"Molecular Structure and Conformations of Benzenesulfonamide: Gas Electron Diffraction and Quantum Chemical Calculations","volume":"71","author":"Petrov","year":"2006","journal-title":"J. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1021\/jp710532z","article-title":"Molecular Structure and Conformations of Para-Methylbenzene Sulfonamide and Ortho-Methylbenzene Sulfonamide: Gas Electron Diffraction and Quantum Chemical Calculations Study","volume":"112","author":"Petrov","year":"2008","journal-title":"J. Phys. Chem. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1021\/jp311789f","article-title":"Conformational Landscape, Photochemistry, and Infrared Spectra of Sulfanilamide","volume":"117","author":"Borba","year":"2013","journal-title":"J. Phys. Chem. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14625","DOI":"10.1039\/C7CP01464C","article-title":"Laser Desorption Single-Conformation UV and IR Spectroscopy of the Sulfonamide Drug Sulfanilamide, the Sulfanilamide-Water Complex, and the Sulfanilamide Dimer","volume":"19","author":"Uhlemann","year":"2017","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_20","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., and Barone, V. (2022, April 09). Gaussian 16, Revision C.01. Available online: https:\/\/gaussian.com\/relnotes\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0022-2852(91)90393-O","article-title":"The Fitting and Prediction of Vibration-Rotation Spectra with Spin Interactions","volume":"148","author":"Pickett","year":"1991","journal-title":"J. Mol. Spectrosc."},{"key":"ref_22","unstructured":"Durig, J.R. (1977). Vibrational Spectra and Structure, Elsevier."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1119\/1.1933338","article-title":"Determination of Molecular Structure from Microwave Spectroscopic Data","volume":"21","author":"Kraitchman","year":"1953","journal-title":"Am. J. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1063\/1.1744602","article-title":"Determination of Molecular Structures from Ground State Rotational Constants","volume":"29","author":"Costain","year":"1958","journal-title":"J. Chem. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jms.2009.10.005","article-title":"A new torsion\u2013rotation fitting program for molecules with a sixfold barrier: Application to the microwave spectrum of toluene","volume":"259","author":"Ilyushin","year":"2010","journal-title":"J. Mol. Spectrosc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/cphc.202000591","article-title":"Large Amplitude Torsions in Nitrotoluene Isomers Studied by Rotational Spectroscopy and Quantum Chemistry Calculations","volume":"21","author":"Roucou","year":"2020","journal-title":"ChemPhysChem"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1515\/zna-1996-0807","article-title":"The Microwave Spectrum of Trans-2,3-Dimethyloxirane in Torsional Excited States","volume":"51","author":"Hartwig","year":"1996","journal-title":"Z. Naturforsch.-Sect. A J. Phys. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1063\/1.1674352","article-title":"Microwave Spectrum, Barrier to Internal Rotation, and Torsion\u2013Vibration Interaction in Ortho-Fluoro Toluene","volume":"53","author":"Susskind","year":"1970","journal-title":"J. Chem. Phys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1006\/jmsp.2002.8600","article-title":"Structural and Torsional Properties of O-Cresol and o-Cresol-OD as Obtained from Microwave Spectroscopy and Ab Initio Calculations","volume":"215","author":"Welzel","year":"2002","journal-title":"J. Mol. Spectrosc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S0022-2852(03)00125-5","article-title":"Internal Rotation and Chlorine Nuclear Quadrupole Coupling of O-Chlorotoluene Studied by Microwave Spectroscopy and Ab Initio Calculations","volume":"220","author":"Gerhard","year":"2003","journal-title":"J. Mol. Spectrosc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0022-2860(94)08516-K","article-title":"A Microwave Free Jet Absorption Spectrometer and Its First Applications","volume":"352\u2013353","author":"Melandri","year":"1995","journal-title":"J. Mol. Struct."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13712","DOI":"10.1021\/jp4078097","article-title":"Keto-Enol Tautomerism and Conformational Landscape of 1,3-Cyclohexanedione from Its Free Jet Millimeter-Wave Absorption Spectrum","volume":"117","author":"Calabrese","year":"2013","journal-title":"J. Phys. Chem. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11674","DOI":"10.1021\/acs.jpca.5b08426","article-title":"The Millimetre Wave Spectrum of the Weakly Bound Complex CH2=CHCN\u00b7H2O: Structure, Dynamics and Implications for Astronomical Search","volume":"119","author":"Calabrese","year":"2015","journal-title":"J. Phys. Chem. A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"053103","DOI":"10.1063\/1.2919120","article-title":"A Broadband Fourier Transform Microwave Spectrometer Based on Chirped Pulse Excitation","volume":"79","author":"Brown","year":"2008","journal-title":"Rev. Sci. Instrum."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"74311","DOI":"10.1063\/1.4961018","article-title":"Structure of Fenchone by Broadband Rotational Spectroscopy","volume":"145","author":"Loru","year":"2016","journal-title":"J. Chem. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jms.2017.03.007","article-title":"Ethanol dimer: Observation of three new conformers by broadband rotational spectroscopy","volume":"335","author":"Loru","year":"2017","journal-title":"J. Mol. Spectrosc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jms.2017.01.005","article-title":"High-J rotational spectrum in |m| \u2264 3 torsional states","volume":"339","author":"Ilyushin","year":"2017","journal-title":"J. Mol. Spectrosc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/ci7002494","article-title":"Small Molecule Conformational Preferences Derived from Crystal Structure Data. A Medicinal Chemistry Focused Analysis","volume":"48","author":"Brameld","year":"2008","journal-title":"J. Chem. Inf. Model."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/9\/2820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:03:35Z","timestamp":1760137415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/9\/2820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["molecules27092820"],"URL":"https:\/\/doi.org\/10.3390\/molecules27092820","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,28]]}}}