{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:16:27Z","timestamp":1787735787307,"version":"build-2784847793"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"JST","doi-asserted-by":"publisher","award":["JPMJAX21KA"],"award-info":[{"award-number":["JPMJAX21KA"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"JST","doi-asserted-by":"publisher","award":["20H00336"],"award-info":[{"award-number":["20H00336"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Japan Ministry of Education, Culture, Sports Science and Technology (MEXT)","doi-asserted-by":"publisher","award":["JPMJAX21KA"],"award-info":[{"award-number":["JPMJAX21KA"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Japan Ministry of Education, Culture, Sports Science and Technology (MEXT)","doi-asserted-by":"publisher","award":["20H00336"],"award-info":[{"award-number":["20H00336"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>The efficient synthesis of amino acid Schiff base copper(II) complexes using a microfluidic device was successfully achieved. Schiff bases and their complexes are remarkable compounds due to their high biological activity and catalytic function. Conventionally, products are synthesized under reaction conditions of 40 \u00b0C for 4 h using a beaker-based method. However, in this paper, we propose using a microfluidic channel to enable quasi-instantaneous synthesis at room temperature (23 \u00b0C). The products were characterized using UV\u2013Vis, FT\u2013IR, and MS spectroscopy. The efficient generation of compounds using microfluidic channels has the potential to significantly contribute to the efficiency of drug discovery and material development due to high reactivity.<\/jats:p>","DOI":"10.3390\/mi14040890","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T04:48:11Z","timestamp":1682052491000},"page":"890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Efficient Synthesis of a Schiff Base Copper(II) Complex Using a Microfluidic Device"],"prefix":"10.3390","volume":"14","author":[{"given":"Masashi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-4912","authenticated-orcid":false,"given":"Takashiro","family":"Akitsu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1221-2874","authenticated-orcid":false,"given":"Masahiro","family":"Furuya","sequence":"additional","affiliation":[{"name":"Cooperative Major in Nuclear Energy, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1, Okubo, Shinjuku-ku, Tokyo 169-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsushi","family":"Sekiguchi","sequence":"additional","affiliation":[{"name":"Research Organization for Nano & Life Innovation, Waseda University, 513 Tsurumakicho, Shinjuku-ku, Tokyo 162-0041, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Shoji","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Tanii","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1900-4848","authenticated-orcid":false,"given":"Daiki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Research Organization for Nano & Life Innovation, Waseda University, 513 Tsurumakicho, Shinjuku-ku, Tokyo 162-0041, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1080\/07391102.2017.1287006","article-title":"Cobalt (II) complex with novel unsymmetrical tetradentate Schiff base (ON) ligand: In vitro cytotoxicity studies of complex, interaction with DNA\/protein, molecular docking studies, and antibacterial activity","volume":"36","author":"Chiniforoshan","year":"2018","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.poly.2017.11.041","article-title":"Syntheses of Zn(II) and Cu(II) Schiff base complexes using N,O donor Schiff base ligand: Crystal structure, DNA binding, DNA cleavage, docking and DFT study","volume":"141","author":"Ghorai","year":"2018","journal-title":"Polyhedron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.saa.2010.12.056","article-title":"A novel bioactive tyramine derived Schiff base and its transition metal complexes as selective DNA binding agents","volume":"78","author":"Raman","year":"2011","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gacit\u00faa, M., Carre\u00f1o, A., Morales-Guevara, R., P\u00e1ez-Hern\u00e1ndez, D., Mart\u00ednez-Araya, J.I., Araya, E., Preite, M., Otero, C., Rivera-Zald\u00edvar, M.M., and Silva, A. (2022). Physicochemical and Theoretical Characterization of a New Small Non-Metal Schiff Base with a Differential Antimicrobial Effect against Gram-Positive Bacteria. Mol. Sci., 23.","DOI":"10.3390\/ijms23052553"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.bmcl.2015.01.010","article-title":"Schiff\u2019s bases of quinazolinone derivatives: Synthesis and SAR studies of a novel series of potential anti-inflammatory and antioxidants","volume":"25","author":"Rakesh","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1016\/j.ejmech.2010.03.036","article-title":"Synthesis, spectral characterization and antimicrobial evaluation of Schiff base Cu (II), Ni (II) and Co (II) complexes","volume":"45","author":"Kumar","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jare.2010.05.004","article-title":"Schiff bases: A short review of their antimicrobial activities","volume":"2","author":"Modolo","year":"2011","journal-title":"J. Adv. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/13543776.2017.1252752","article-title":"Schiff bases in medicinal chemistry: A patent review (2010\u20132015)","volume":"27","author":"Hameed","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7482","DOI":"10.1016\/j.bmc.2006.07.015","article-title":"Synthesis and biological activity of Schiff and Mannich bases bearing 2,4-dichloro-5-fluorophenyl moiety","volume":"14","author":"Karthikeyan","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1016\/j.ejmech.2010.07.058","article-title":"Synthesis, antiviral activity and cytotoxicity evaluation of Schiff bases of some 2-phenyl quinazoline-4(3)H-ones","volume":"45","author":"Kumar","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.ccr.2007.09.005","article-title":"Catalytic activities of Schiff base transition metal complexes","volume":"252","author":"Gupta","year":"2008","journal-title":"Coord. Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccr.2015.11.010","article-title":"Schiff base-derived homogeneous and heterogeneous palladium catalysts for the Suzuki\u2013Miyaura reaction","volume":"311","author":"Das","year":"2016","journal-title":"Coord. Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6403","DOI":"10.1016\/j.tetlet.2010.09.109","article-title":"Effective oxidation of alcohols by Iron(III)-Schiff base-triphenylphosphine complexes","volume":"51","author":"Rani","year":"2010","journal-title":"Tetrahedron Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.saa.2012.09.085","article-title":"Synthesis, spectral characterization and antioxidant activity studies of a bidentate Schiff base, 5-methyl thiophene-2-carboxaldehyde-carbohydrazone and its Cd(II), Cu(II), Ni(II) and Zn(II) complexes","volume":"101","author":"Harinath","year":"2013","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.saa.2013.03.061","article-title":"Design, characterization, teratogenicity testing, antibacterial, antifungal and DNA interaction of few high spin Fe(II) Schiff base amino acid complexes","volume":"111","author":"Nassr","year":"2013","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s13738-014-0557-9","article-title":"Tailoring, physicochemical characterization, antibacterial and DNA binding mode studies of Cu(II) Schiff bases amino acid bioactive agents incorporating 5-bromo-2-hydroxybenzaldehyde","volume":"12","author":"Nassr","year":"2015","journal-title":"J. Iran. Chem. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Onami, Y., Koya, R., Kawasaki, T., Aizawa, H., Nakagame, R., Miyagawa, Y., Haraguchi, T., Akitsu, T., Tsukiyama, K., and Palafox, M.A. (2019). Investigation by DFT Methods of the Damage of Human Serum Albumin Including Amino Acid Derivative Schiff Base Zn(II) Complexes by IR-FEL Irradiation. Mol. Sci., 20.","DOI":"10.3390\/ijms20112846"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1007\/s11172-017-1981-7","article-title":"Photo-induced reduction of Cr6+ by the hybrid systems \u201cCuII complex with Schiff base and TiO2\u201d: Dependence on irradiation wavelength","volume":"66","author":"Yoshida","year":"2017","journal-title":"Russ. Chem. Bull."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/(SICI)1098-1136(199709)21:1<92::AID-GLIA10>3.0.CO;2-W","article-title":"Brain metabolism of branched-chain amino acids","volume":"21","author":"Yudkoff","year":"1997","journal-title":"Glia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.3389\/fendo.2013.00102","article-title":"Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA","volume":"4","author":"Schousboe","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.biopha.2018.08.051","article-title":"Acute toxic effects of ruthenium (II)\/amino acid\/diphosphine complexes on Swiss mice and zebrafish embryos","volume":"107","author":"Cardoso","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s00775-017-1483-y","article-title":"Anticancer activity of novel amino acid derivative of palladium complex with phendione ligand against of human colon cancer cell line","volume":"22","author":"Farhangian","year":"2017","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_23","first-page":"119","article-title":"A review on versatile applications of transition metal complexes incorporating Schiff bases","volume":"4","author":"Mohamed","year":"2015","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6202","DOI":"10.1038\/s41467-020-19926-z","article-title":"A droplet microfluidic platform for high-throughput photochemical reaction discovery","volume":"11","author":"Sun","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrd.2017.232","article-title":"Automating drug discovery","volume":"17","author":"Schneider","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7468","DOI":"10.1021\/acs.chemrev.0c01289","article-title":"Microfluidics for Drug Development: From Synthesis to Evaluation","volume":"121","author":"Liu","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nature05062","article-title":"Control and detection of chemical reactions in microfluidic systems","volume":"442","author":"Demello","year":"2006","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41570-021-00343-9","article-title":"Reconfigurable microfluidics","volume":"6","author":"Paratore","year":"2022","journal-title":"Nat. Rev. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16708","DOI":"10.1039\/C9NR06817A","article-title":"Self-assembly of colloids based on microfluidics","volume":"11","author":"Wang","year":"2019","journal-title":"Nanoscale"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.1002\/smll.201500527","article-title":"Continuous Microfluidic Self-Assembly of Hybrid Janus-Like Vesicular Motors: Autonomous Propulsion and Controlled Release","volume":"11","author":"Wang","year":"2015","journal-title":"Small"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0006-3495(01)76003-1","article-title":"Theoretical Analysis of Molecular Diffusion in Pressure-Driven Laminar Flow in Microfluidic Channels","volume":"80","author":"Kamholz","year":"2001","journal-title":"Biophys. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3270","DOI":"10.1021\/ac702469u","article-title":"Enzymatic Reactions in Microfluidic Devices:\u2009 Michaelis\u2212Menten Kinetics","volume":"80","author":"Ristenpart","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/ange.200390172","article-title":"A Microfluidic System for Controlling Reaction Networks in Time","volume":"115","author":"Song","year":"2003","journal-title":"Angew. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1021\/ac102472a","article-title":"Enzyme Kinetic Measurements Using a Droplet-Based Microfluidic System with a Concentration Gradient","volume":"83","author":"Bui","year":"2011","journal-title":"Anal. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.cej.2017.10.085","article-title":"Enhanced enzymatic reaction by aqueous two-phase systems using parallel-laminar flow in a double Y-branched microfluidic device","volume":"355","author":"Meng","year":"2018","journal-title":"Chem. Eng. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1021\/ol3005529","article-title":"Application of Microflow Conditions to Visible Light Photoredox Catalysis","volume":"14","author":"Neumann","year":"2012","journal-title":"Org. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shao, F., Hsieh, K., Zhang, P., Kaushik, A.M., and Wang, T.H. (2021, January 20\u201324). A Tubing-Free Sample-to-Droplet Interface Enables Facile Sample Loading of Droplet Microfluidics Device Toward High-Throughput Screening. Proceedings of the 2021 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers), Orlando, FL, USA.","DOI":"10.1109\/Transducers50396.2021.9495609"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1039\/b921695b","article-title":"Microfluidic cell culture systems for drug research","volume":"10","author":"Wu","year":"2010","journal-title":"Lab Chip"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.chempr.2017.01.009","article-title":"Small but Perfectly Formed? Successes, Challenges, and Opportunities for Microfluidics in the Chemical and Biological Sciences","volume":"2","author":"Chiu","year":"2017","journal-title":"Chem"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29966","DOI":"10.1039\/C7RA04494A","article-title":"Concentration gradient generation methods based on microfluidic systems","volume":"7","author":"Wang","year":"2017","journal-title":"RSC Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1039\/C5LC00045A","article-title":"Mixing with herringbone-inspired microstructures: Overcoming the diffusion limit in co-laminar microfluidic devices","volume":"15","author":"Marschewski","year":"2015","journal-title":"Lab Chip"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"094001","DOI":"10.1088\/0960-1317\/25\/9\/094001","article-title":"Mixing in microfluidic devices and enhancement methods","volume":"25","author":"Ward","year":"2015","journal-title":"J. Micromech. Microeng."}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/14\/4\/890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:31Z","timestamp":1760124031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/14\/4\/890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["mi14040890"],"URL":"https:\/\/doi.org\/10.3390\/mi14040890","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}