Ln(III) complexes of macrocyclic ligands are used in medicinal chemistry, for example as contrast agents in MRI or radiopharmaceutical compounds, and in diagnostics using fluorescence imaging. This paper is devoted to a spectroscopic study of Ln(III) ternary complexes consisting of macrocyclic heptadentate DO3A and bidentate 3-isoquinolinate (IQCA) ligands. IQCA serves as an efficient antenna ligand, leading to a higher quantum yield and Stokes shift (250-350 nm for Eu, Tb, Sm, Dy in VIS region, 550-650 nm for Yb, Nd in NIR region). The shielding-quenching effect of NAD(P)H on the luminescence of the Ln(III) ternary complexes was investigated in detail and this phenomenon was utilized for the analytical determination of this compound. This general approach was verified through an enzymatic reaction during which the course of ethanol transformation catalyzed by alcohol-dehydrogenase (ADH) was followed by luminescence spectroscopy. This method can be utilized for selective and sensitive determination of ethanol concentration and/or ADH enzyme activity. This new analytical method can also be used for other enzyme systems coupled with NAD(P)H/NAD(P)+ redox pairs.

Department of Chemistry Faculty of Science Masaryk University Kamenice 5 625 00 Brno Czech Republic

Zobrazit více v PubMed

Bűnzli J.C., Piguet C. Taking advantage of luminescent lanthanide ions. Chem. Soc. Rev. 2005;34:1048–1077. doi: 10.1039/b406082m. PubMed DOI

Bűnzli J.C. Lanthanide Luminescence for Biomedical Analyses and Imaging. Chem. Rev. 2010;110:2729–2755. doi: 10.1021/cr900362e. PubMed DOI

Bűnzli J.C., Eliseeva S.V. Lanthanide NIR luminescence for telecommunications, bioanalyses and solar energy conversion. J. Rare Earths. 2010;28:824–832. doi: 10.1016/S1002-0721(09)60208-8. DOI

Bűnzli J.C. On the design of highly luminescent lanthanide complexes. Coord. Chem. Rev. 2015;293–294:19–47. doi: 10.1016/j.ccr.2014.10.013. DOI

Sigel A.S.H., Pyle A.M., Sigel A., Sigel H. The Lanthanides and Their Interrelations with Biosystems. In: Sigel A., Sigel H., editors. Metal Ions in Biological Systems. Volume 40 Marcel Dekker; New York, NY, USA: 2003.

Shuvaev S., Starck M., Parker D. Responsive, water-soluble Europium(III) luminescent probes. Chem. Eur. J. 2017;23:9974–9989. doi: 10.1002/chem.201700567. PubMed DOI

New E., Parker D., Smith D.G., Walton J.W. Development of responsive lanthanide probes for cellular applications. Curr. Opin. Chem. Biol. 2010;14:238–246. doi: 10.1016/j.cbpa.2009.10.003. PubMed DOI

Montgomery C.P., Murray B.S., New E.J., Pal R., Parker D. Cell-Penetrating Metal Complex Optical Probes: Targeted and Responsive Systems Based on Lanthanide Luminescence. Acc. Chem. Res. 2009;42:925–937. doi: 10.1021/ar800174z. PubMed DOI

Mathieu E., Sipos A., Demeyere E., Phipps D., Sakaveli D., Borbas K.E. Lanthanide-based tools for the investigation of cellular environments. Chem. Commun. 2018;54:10021–10035. doi: 10.1039/C8CC05271A. PubMed DOI

Thibon A., Pierre V.C. Principles of responsive lanthanide-based luminescent probes for cellular imaging. Anal. Bioanal. Chem. 2009;394:107–120. doi: 10.1007/s00216-009-2683-2. PubMed DOI

Hefern M.C., Matosziuk L.M., Meade T.J. Lanthanide probes for bioresponsive imaging. Chem. Rev. 2014;114:4496–4539. doi: 10.1021/cr400477t. PubMed DOI PMC

Hewit S.H., Butler S.J. Application of lanthanide luminescence in probing enzyme activity. Chem. Commun. 2018;54:6635–6647. doi: 10.1039/C8CC02824A. PubMed DOI

Zwier J.M., Bazin H., Lamarque L., Mathis G. Luminescent lanthanide cryptates: From the bench to the bedside. Inorg. Chem. 2014;53:1854–1866. doi: 10.1021/ic402234k. PubMed DOI

Kovacs D., Lu X., Meszaros L.S., Ott M., Andres J., Borbas K.E. Photophysics of Coumarin and Carbostyril-Sensitized Luminescent Lanthanide Complexes: Implications for Complex Design in Multiplex Detection. J. Am. Chem. Soc. 2017;139:5756–5767. doi: 10.1021/jacs.6b11274. PubMed DOI

Pershagen E., Borbas K.E. Multiplex Detection of Enzymatic Activity with Responsive Lanthanide-Based Luminescent Probes. Angew. Chem. Int. Ed. 2015;54:1787–1790. doi: 10.1002/anie.201408560. PubMed DOI

Pershagen E., Nordholm J., Borbas K.E. Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation. J. Am. Chem. Soc. 2012;134:9832–9835. doi: 10.1021/ja3004045. PubMed DOI

Gunnlaugsson T., Leonard J.P. Responsive lanthanide luminescent cyclen complexes: From switching/sensing to supramolecular architectures. Chem. Commun. 2005:3114–3131. doi: 10.1039/b418196d. PubMed DOI

Stasiuk G.J., Long N.J. The ubiquitous DOTA and its derivatives: The impact of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid on biomedical imaging. Chem. Commun. 2013;49:2732–2746. doi: 10.1039/c3cc38507h. PubMed DOI

Brücher E., Baranyai Z., Tircsó G. The future of biomedical imaging: Synthesis and chemical properties of the DTPA and DOTA derivative ligands and their complexes. In: Braddock M., editor. Biomedical Imaging: The Chemistry of Labels, Probes, and Contrast Agents. Royal Society of Chemistry; Cambridge, UK: 2012. pp. 208–260. Chapter 5.2.

Táborský P., Svobodová I., Lubal P., Hnatejko Z., Lis S., Hermann P. Formation and dissociation kinetics of Eu(III) complexes with H5do3ap and similar dota-like ligands. Polyhedron. 2007;26:4119–4130. doi: 10.1016/j.poly.2007.05.014. DOI

Mamedov I., Táborský P., Lubal P., Laurent S., Elst L.V., Mayer H.A., Logothetis N.K., Angelovski G. Relaxometric, Thermodynamic and Kinetic Studies of Lanthanide(III) Complexes of DO3A-Based Propylphosphonates. Eur. J. Inorg. Chem. 2009:3298–3306. doi: 10.1002/ejic.200900149. DOI

Campello M.P.C., Lacerda S., Santos I.C., Pereira G.A., Geraldes C.F.G.C., Kotek J., Hermann P., Vaněk J., Lubal P., Kubíček V., et al. Lanthanide(III) Complexes of 4,10-Bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (trans-H6do2a2p) in Solution and in the Solid State: Structural Studies Along the Series. Chem. Eur. J. 2010;16:8446–8465. doi: 10.1002/chem.201000320. PubMed DOI

Vaněk J., Lubal P., Ševčíková R., Polášek M., Hermann P. Mono(pyridine-N-oxide) analog of DOTA as a suitable organic reagent for a sensitive and selective fluorimetric determination of Ln(III) ions. J. Lumin. 2012;132:2030–2035. doi: 10.1016/j.jlumin.2012.03.018. DOI

Smrčka F., Lubal P. The time-resolved fluorescence study of kinetics and thermodynamics of Eu(III) and Tb(III) complexes with the DO2A macrocyclic ligand. New J. Chem. 2018;42:7993–8000. doi: 10.1039/C8NJ00255J. DOI

Försterová M., Jandurová Z., Marques F., Gano L., Lubal P., Vaněk J., Hermann P., Santos I. Chemical and biological evaluation of 153Sm and 166Ho complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid monoethylester) (H4dotpOEt) J. Inorg. Biochem. 2008;102:1531–1540. doi: 10.1016/j.jinorgbio.2008.02.002. PubMed DOI

Merbach A.E., Helm L., Tóth E. The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging. Willey; Hoboken, NJ, USA: 2013.

Hermann P., Kotek J., Kubíček V., Lukeš I. Gadolinium(III) complexes as MRI contrast agents: Ligand design and properties of the complexes. Dalton Trans. 2008;23:3027–3047. doi: 10.1039/b719704g. PubMed DOI

Vaněk J., Lubal P., Hermann P., Anzenbacher P., Jr. Luminescent Sensor for Carbonate Ion Based on Lanthanide(III) Complexes of 1,4,7,10-Tetraazacyclododecane-1,4,7-Triacetic Acid (DO3A) J. Fluoresc. 2013;23:57–69. doi: 10.1007/s10895-012-1116-3. PubMed DOI

Vaněk J., Smrčka F., Lubal P., Třísková I., Trnková L. Dual carbonate sensor based on Eu(III) complex of DO3A ligand. Mon. Chem. 2016;147:925–934. doi: 10.1007/s00706-016-1722-x. DOI

Smrčka F., Lubal P., Šídlo M. The urea biosensor based on luminescence of Eu(III) ternary complex of DO3A ligand. Mon. Chem. 2017;148:1945–1952. doi: 10.1007/s00706-017-2043-4. DOI

Stryer L. Biochemistry. Freeman; New York, NY, USA: 1988.

Banerjee R. Redox Biochemistry. Willey; Hoboken, NJ, USA: 2008.

Blinova K., Carroll S., Bose S., Smirnov A.V., Harvey J.J., Knutson J.R., Balaban R.S. Distribution of mitochondrial NADH fluorescence lifetimes: Steady-state kinetics of matrix NADH interactions. Biochemistry. 2005;44:2585–2594. doi: 10.1021/bi0485124. PubMed DOI

Blacker T.S., Berecz T., Duchen M.R., Szabadkai G. Assessment of Cellular Redox State Using NAD(P)H Fluorescence Intensity and Lifetime. Bio-Protoc. 2017;7:e2105. doi: 10.21769/BioProtoc.2105. PubMed DOI PMC

Sharma A., Quantrill N.S.M. Measurement of ethanol using fluorescence quenching. Spectrochim. Acta A. 1994;50:1161–1177. doi: 10.1016/0584-8539(94)80038-3. DOI

Lee S.-L., Shih H.-T., Chi Y.-C., Li Y.-P., Yin S.-J. Oxidation of methanol, ethylene glycol, and isopropanol with human alcohol dehydrogenases and the inhibition by ethanol and 4-methylpyrazole. Chem-Biol. Interact. 2011;191:26–31. doi: 10.1016/j.cbi.2010.12.005. PubMed DOI

Sharma A., Arnold M.A. Fluorescence quenching of thionine by reduced nicotinamide adenine-dinucleotide. Spectrochim. Acta A. 1992;48:647–651. doi: 10.1016/0584-8539(92)80209-F. DOI

Sharma A. Photolytic oxidation of reduced nicotinamide adenine-dinucleotide. Spectrochim. Acta A. 1992;48:893–897. doi: 10.1016/0584-8539(92)80086-C. DOI

Kudoa H., Sawai M., Suzuki Y., Wang X., Gessei T., Takahashi D., Arakawa T., Mitsubayashi K. Fiber-optic bio-sniffer (biochemical gas sensor) for high-selective monitoring of ethanol vapor using 335nm UV-LED. Sens. Actuators B. 2010;147:676–680. doi: 10.1016/j.snb.2010.03.066. DOI

Iitani K., Chien P.-J., Suzuki T., Toma K., Arakawa T., Iwasaki Y., Mitsubayashi K. Improved Sensitivity of Acetaldehyde Biosensor by Detecting ADH Reverse Reaction-Mediated NADH Fluoro-Quenching for Wine Evaluation. ACS Sens. 2017;2:940–946. doi: 10.1021/acssensors.7b00184. PubMed DOI

Thungon P.D., Kakoti A., Ngashangva L., Goswami P. Advances in developing rapid, reliable and portable detection systems for alcohol. Biosens. Bioelectr. 2017;97:83–99. doi: 10.1016/j.bios.2017.05.041. PubMed DOI

Martins A.F., Eliseeva S.V., Carvalho H.F., Teixeira J.M.C., Paula C.T.B., Hermann P., Platas-Iglesias C., Petoud S., Tóth E., Geraldes C.F.G.C. A Bis(pyridine N-oxide) Analogue of DOTA: Relaxometric Properties of the Gd-III Complex and Efficient Sensitization of Visible and NIR-Emitting Lanthanide(III) Cations Including Pr(III) and Ho(III) Chem. Eur. J. 2014;20:14834–14845. doi: 10.1002/chem.201403856. PubMed DOI

Hashami Z., Martins A.F., Funk A.M., Jordan V.C., Petoud S., Eliseeva S.V., Kovacs Z. Lanthanide DO3A-Tropolone Complexes: Efficient Dual MR/NIR Imaging Probes in Aqueous Medium. Eur. J. Inorg. Chem. 2017:4965–4968. doi: 10.1002/ejic.201701003. PubMed DOI PMC

Peterson K.L., Margherio M.J., Doan P., Wilke K.T., Pierre V.C. Basis for Sensitive and Selective Time-Delayed Luminescence of Hydroxyl Radical by Lanthanide Complexes. Inorg. Chem. 2013;52:9390–9398. doi: 10.1021/ic4009569. PubMed DOI PMC

Supkowski R.M., de Horrocks W.W., Jr. Lanthanide Ions of Electron Transfer in Proteins. In: Sigel A., Sigel H., editors. Metal Ions in Biological Systems. Volume 40 Marcel Dekker; New York, NY, USA: 2003. PubMed

Krausková L., Procházková J., Klásková M., Filipová L., Chaloupková R., Malý S., Damborský J., Heger D. Suppression of protein inactivation during freezing by minimizing pH changes using ionic cryoprotectants. Int. J. Pharm. 2016;509:41–49. doi: 10.1016/j.ijpharm.2016.05.031. PubMed DOI