{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T21:22:10Z","timestamp":1773350530362,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["21H05006"],"award-info":[{"award-number":["21H05006"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>A taste sensor with lipid\/polymer membranes is attracting attention as a method to evaluate taste objectively. However, due to the characteristic of detecting taste by changes in membrane potential, taste sensors cannot measure non-charged bitter substances. Many foods and medicines contain non-charged bitter substances, and it is necessary to quantify these tastes with sensors. Therefore, we have been developing taste sensors to detect bitter tastes caused by non-charged substances such as caffeine. In previous studies, a sensor for detecting bitterness caused by caffeine and theobromine, theophylline, was developed, using a membrane modified with hydroxybenzoic acid (HBA) as the sensing part. The sensor was designed to form intramolecular hydrogen bonds (H-bonds) between the hydroxy group and carboxy group of HBA and to successively cause the intermolecular H-bonds between HBA and caffeine molecules to be measured. However, whether this sensing principle is correct or not cannot be confirmed from the results of taste sensor measurements. Therefore, in this study, we explored the interaction between HBA and caffeine by 1H-nuclear magnetic resonance spectroscopy (NMR). By the 1H NMR detection, we confirmed that both the substances interact with each other. Furthermore, the nuclear Overhauser effect (NOE) of intermolecular spatial conformation in solution was measured, by which 2,6-dihydroxybenzoic acid (2,6-DHBA) preferably interacted with caffeine via the H-bonding and stacking configuration between aromatic rings. Identifying the binding form of 2,6-DHBA to caffeine was estimated to predict how the two substances interact.<\/jats:p>","DOI":"10.3390\/s22072592","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:45:51Z","timestamp":1648590351000},"page":"2592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Identification of the Principle of Taste Sensors to Detect Non-Charged Bitter Substances by 1H-NMR Measurement"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6640-353X","authenticated-orcid":false,"given":"Misaki","family":"Ishida","sequence":"first","affiliation":[{"name":"Graduate School of Information Science and Electrical Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"}]},{"given":"Haruna","family":"Ide","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"}]},{"given":"Keishiro","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"}]},{"given":"Zeyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Graduate School of Information Science and Electrical Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"}]},{"given":"Toshiro","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"},{"name":"Research and Development Center for Five-Sense Devices, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"}]},{"given":"Kiyoshi","family":"Toko","sequence":"additional","affiliation":[{"name":"Research and Development Center for Five-Sense Devices, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"},{"name":"Institute for Advanced Study, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ref_1","unstructured":"Flavio, M.S., and Maria, L.B.A.R. (2021). A First Taste to Electronic Tongues. Electronic Tongues, IOP."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2116\/analsci.19R008","article-title":"Taste Sensor: Electronic Tongue with Lipid Membranes","volume":"36","author":"Wu","year":"2020","journal-title":"Anal. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Toko, K., Tahara, Y., Habara, M., Kobayashi, Y., and Ikezaki, H. (2016). Taste Sensor: Electronic Tongue with Global Selectivity. Essentials of Machine Olfaction and Taste, Wiley.","DOI":"10.1002\/9781118768495.ch4"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.microc.2013.04.018","article-title":"Development and Application of an Electronic Tongue for Detection and Monitoring of Nitrate, Nitrite and Ammonium Levels in Waters","volume":"110","author":"Pividori","year":"2013","journal-title":"Microchem. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1109\/JSEN.2013.2263125","article-title":"Electronic Tongues\u2014A Review","volume":"13","author":"Tahara","year":"2013","journal-title":"IEEE Sens. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jpba.2011.02.002","article-title":"A Comparative Study on Two Electronic Tongues for Pharmaceutical Formulation Development","volume":"55","author":"Woertz","year":"2011","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1039\/b705107g","article-title":"Sensor Arrays for Liquid Sensing\u2014Electronic Tongue Systems","volume":"132","author":"Ciosek","year":"2007","journal-title":"Analyst"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0925-4005(99)00508-0","article-title":"Taste Sensor","volume":"64","author":"Toko","year":"2000","journal-title":"Sens. Actuators B Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"128228","DOI":"10.1016\/j.foodchem.2020.128228","article-title":"Bitterness Compounds in Coffee Brew Measured by Analytical Instruments and Taste Sensing System","volume":"342","author":"Fujimoto","year":"2021","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"127784","DOI":"10.1016\/j.snb.2020.127784","article-title":"Quantification of Bitterness of Coffee in the Presence of High-Potency Sweeteners Using Taste Sensors","volume":"309","author":"Wu","year":"2020","journal-title":"Sens. Actuators B Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yoshimatsu, J., Toko, K., Tahara, Y., Ishida, M., Habara, M., Ikezaki, H., Kojima, H., Ikegami, S., Yoshida, M., and Uchida, T. (2020). Development of Taste Sensor to Detect Non-Charged Bitter Substances. Sensors, 20.","DOI":"10.3390\/s20123455"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Ishida, M., Onodera, T., and Toko, K. (2022). Effect of Hydroxybenzoic Acids on Caffeine Detection Using Taste Sensor with Lipid\/polymer Membranes. Sensors, 22.","DOI":"10.3390\/s22041607"},{"key":"ref_13","first-page":"171","article-title":"Development of Caffeine Detection Using Taste Sensor with Lipid\/Polymer Membranes","volume":"20","author":"Shen","year":"2008","journal-title":"Sens. Mater."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Emwas, A.H., Roy, R., McKay, R.T., Tenori, L., Saccenti, E., Nagana Gowda, G.A., Raftery, D., Alahmari, F., Jaremko, L., and Jaremko, M. (2019). NMR spectroscopy for metabolomics research. Metabolites, 9.","DOI":"10.3390\/metabo9070123"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.2116\/analsci.20P163","article-title":"Ligand-aided 1H Nuclear Magnetic Resonance Spectroscopy for Non-destructive Estimation of Sulfate Content in Sulfated Saccharides","volume":"36","author":"Bak","year":"2020","journal-title":"Anal. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1021\/ol026373h","article-title":"Tripodal Nitro-Imidazolium Receptor for Anion Binding Driven by (C-H) + X-Hydrogen Bonds","volume":"4","author":"Ihm","year":"2002","journal-title":"Org. Lett."},{"key":"ref_17","first-page":"370","article-title":"Selection of Coherence-Transfer Pathways in NMR Pulse Experiments","volume":"58","author":"Bodenhausen","year":"1984","journal-title":"J. Magn. Reson."},{"key":"ref_18","first-page":"286","article-title":"A 2D Nuclear Overhauser Experiment with Pure Absorption Phase in Four Quadrants","volume":"48","author":"States","year":"1982","journal-title":"J. Magn. Reson."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4546","DOI":"10.1063\/1.438208","article-title":"Investigation of Exchange Processes by Two-Dimensional NMR Spectroscopy","volume":"71","author":"Jeener","year":"1979","journal-title":"J. Chem. Phys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/jps.21824","article-title":"Effect of Position Isomerism on the Formation and Physicochemical Properties of Pharmaceutical Co-crystals","volume":"99","author":"Liao","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1021\/cg801178m","article-title":"Cocrystals of Caffeine and Hydroxybenzoic Acids Composed of Multiple Supramolecular Heterosynthons: Screening via Solution-Mediated Phase Transformation and Structural Characterization","volume":"9","author":"Henry","year":"2009","journal-title":"Cryst. Growth Des."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/22\/7\/2592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:45:09Z","timestamp":1760136309000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/22\/7\/2592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,28]]},"references-count":21,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["s22072592"],"URL":"https:\/\/doi.org\/10.3390\/s22072592","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,28]]}}}