Study on the Development of a Cyclohexane Based Tripodal Molecular Device as "OFF-ON-OFF" pH Sensor and Fluorescent Iron Sensor

Author(s): Vijay Dangi, Minati Baral*, B.K. Kanungo

Journal Name: Current Analytical Chemistry

Volume 16 , Issue 5 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Background: Iron is an essential transition metal which is indispensable for life processes like oxygen transport and metabolism, electron transfer etc. However, misregulated iron is responsible for disease like anemia, hemochromatosis, Alzheimer’s and Parkinson’s disease. In order to encounter these diseases, a better understanding is needed of its role in misregulation. Fluorescent iron sensors could help provide this information. The new chemosensor developed by linking a cyclohexane unit with three 8-hydroxyquinoline provides selective detection of iron in numerous biological and environmental samples.

Methods: The Uv-visible and fluorescence spectroscopy in combination with pH measurements will mainly be used for the study. Theoretical studies at DFT level will be used to validate the method and explain the theory behind the experiments.

Results: The study of electronic spectra of the chelator, HQCC, reveals the appearance of a band at 262 nm along with a weak band at 335 nm due to π- π* and n- π* transitions respectively. Upon excitation with 335 nm, the ligand fluoresces at 388 nm wavelength. The intensity of the emission was affected in presence of metal ions, with maximum deviation for Fe(III). Selectivity studies showed that Fe(III) is more selective as compared to the biologically relevant metal ions viz., Al(III), Fe(III), Cr(III), Co(II), Fe(II), Ni(II), Zn(II), Cu(II), Mn(II) and Pb(II). pH dependent studies implied that the fluorescence intensity was highest at pH ~8.0, whereas maximum quenching for iron-HQCC system was observed at pH 7.4. The binding studies from the B-H plot confirms the formation of 1:1 complex with association constant of 5.95 × 106. The results obtained from experiments were in agreement with that obtained from the DFT and TD-DFT studies.

Conclusion: A novel tripodal chelator based on 8-hydroxyquinoline and symmetric cyclohexane scaffold was successfully developed. In addition to the excellence of the ligand to be employed as a promising sensitive fluorescent probe for easy detection of Fe3+ions at the physiological pH with very low concentration (7.5 x 10-5 molL-1), the new ligand can be used as an OFF-ON-OFF pH sensor. Fe(III) encapsulation along with 1:1 ML-complexation formation have been established. Theoretical studies confirm a d-PET mechanism for the fluorescence quenching. DFT studies revealed that the neutral form of the ligand is less reactive than its protonated or the deprotonated form.

Keywords: DFT, OFF-ON-OFF, PET, sensor, tripodal, ZINDO.

Liu, X.; Theil, E.C. Ferritins: dynamic management of biological iron and oxygen chemistry. Acc. Chem. Res., 2005, 38, 167-175.
Gray, H.B.; Winkler, J.R. Electron transfer in proteins. Annu. Rev. Biochem., 1996, 65, 537-561.
Kaplan, C.D.; Kaplan, J. Iron acquisition and transcriptional regulation. Chem. Rev., 2009, 109, 4536-4552.
Praveen, L.; Reddy, M.L.P.; Luxmi Varma, R. Dansyl-styrylquinoline conjugate as divalent iron sensor. Tetrahedron Lett., 2010, 51, 6626-6629.
Grabchev, I.; Chovelon, J.M.; Qian, X. A copolymer of 4-N,N-dimethylaminoethylene-N-allyl-1,8-naphthalimide with methylmethacrylate as a selective fluorescent chemosensor in homogeneous systems for metal cations. J. Photochem. Photobiol. Chem., 2003, 158, 37-43.
Kikkeri, R.; Traboulsi, H.; Humbert, N. Toward iron sensors: bioinspired tripods based on fluorescent phenol-oxazoline coordination sites. Inorg. Chem., 2007, 46, 2485-2497.
Vairaperumal, T.; Kasi, P. An acyclic, dansyl based colorimetric and fluorescent chemosensor for Hg(II) via twisted intramolecular charge transfer (TICT). Anal. Chim. Acta, 2012, 751, 171-175.
Wang, H.; Lin, J.; Huang, W.; Wei, W. Fluorescence “turn-on” metal ion sensors based on switching of intramolecular charge transfer of donor-acceptor systems. Sens. Actuators B Chem., 2010, 150, 798-805.
Chen, Y.; Sun, Z-H.; Song, B-E.; Liu, Y. Naphthylthiourea-modified permethylcyclodextrin as a highly sensitive and selective “turn-on” fluorescent chemosensor for Hg2+ in water and living cells. Org. Biomol. Chem., 2011, 9, 5530-5534.
Chung, S.K.; Tseng, Y.R.; Chen, C.Y.; Sun, S.S. A selective colorimetric Hg2+ probe featuring a styryl dithiaazacrown containing platinum (II) terpyridine complex through modulation of the relative strength of ICT and MLCT transitions. Inorg. Chem., 2011, 50, 2711-2713.
Pandey, S.; Azam, A.; Pandey, S.; Chawla, H.M. Novel dansyl-appended calix[4]arene frameworks: fluorescence properties and mercury sensing. Org. Biomol. Chem., 2009, 7, 269-279.
Liu, B.; Zeng, F.; Wu, G.; Wu, S. A FRET-based ratiometric sensor for mercury ions in water with multi-layered silica nanoparticles as the scaffold. Chem. Commun. (Camb.), 2011, 47, 8913-8915.
Praveen, L.; Suresh, C.H.; Reddy, M.L.P.; Luxmi Varma, R. Molecular fluorescent probe for Zn2+ based on 2-(2-nitrostyryl)-8-methoxyquinoline. Tetrahedron Lett., 2011, 52, 4730-4733.
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Chesseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Peterson, G.A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.P.; Izmaylov, A.F.; Bloino, J.; Zheng, G.; Sonnenberg, J.L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J.A.; Peralta, J.E., Jr; Ogliaro, F.; Bearpark, M.; Heyd, J.J.; Brothers, E.; Kudin, K.N.; Staroverov, V.N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J.C.; Iyengar, S.S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J.M.; Klene, M.; Knox, J.E.; Cross, J.B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.E.; Yazyev, O.; Austin, A.J.; Cammi, R.; Pomelli, C.; Ochterski, J.W.; Martin, R.L.; Morokuma, K.; Zakrzewski, V.G.; Voth, G.A.; Salvador, P.; Dannenberg, J.J.; Dapprich, S.; Daniels, A.D.; Farkas, O.; Foresman, J.B.; Ortiz, J.V.; Cioslowski, J.; Fox, D.J. Gaussian 09; Revision A.I. Gaussian Inc: Wallingford, CT, 2009.
Becke, A.D. Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev., 1998, 38, 3098-3100.
Benesi, H.A.; Hildebrand, J.H. A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. J. Am. Chem. Soc., 1949, 71, 2703-2707.
Kumar, P.; Kumar, V.; Gupta, R. Arene-based fluorescent probes for the selective detection of iron. RSC Advances, 2015, 5, 97874-97882.
Buemi, G.; Zuccarello, F.; Venuvanalingam, P.; Ramalingam, M. Ab initio study of tautomerism and hydrogen bonding of β-carbonylamine in the gas phase and in water solution. Theor. Chem. Acc., 2000, 104, 226-234.
Sheikhshoaie, I.; Fabian, W.M.F. Theoretical insights into material properties of Schiff bases and related azo compounds. Curr. Org. Chem., 2009, 13, 149-171.
Filarowski, A.; Koll, A.; Sobczyk, L. Intramolecular hydrogen bonding in o-hydroxy aryl Schiff bases. Curr. Org. Chem., 2009, 13, 172-193.
Musin, R.N.; Mariam, Y.H. An integrated approach to the study of intramolecular hydrogen bonds in malonaldehyde enol derivatives and naphthazarin: trend in energetic versus geometrical consequences. J. Phys. Org. Chem., 2006, 19, 425-444.
Raisi, H.; Moshfeghi, E.; Jalbout, A.F.; Hosseini, M.S.; Fazli, M. An approach to estimate the energy and strength of the intramolecular hydrogen bond in different conformers of 4‐methylamino‐3‐penten‐2‐one. Int. J. Quantum Chem., 2007, 107, 1835-1845.
Lenain, P.; Mandado, M.; Mosquera, R.A.; Bultinck, P. Interplay between hydrogen-bond formation and multicenter π-electron delocalization: intramolecular hydrogen bonds. J. Phys. Chem. A, 2008, 112, 10689-10696.
Rybarczyk-Pirek, J.; Grabowski, S.J.; Malecka, M.; Nawrot-Modranka, J. Crystal and molecular structures of new chromone derivatives as empirical evidence of intramolecular proton transfer reaction; ab initio studies on intramolecular h-bonds in enaminones. J. Phys. Chem. A, 2002, 106, 11956-11962.
Nowroozi, A.; Raissi, H.; Farzad, F. The presentation of an approach for estimating the intramolecular hydrogen bond strength in conformational study of β-Aminoacrolein. J. Mol. Struct. THEOCHEM, 2005, 730, 161-169.
Nunez, C.; Fernandez-Lodeiro, J.; Dinis, M.; Capelo, J.L.; Lodeiro, C. Synthesis and photophysical studies of two luminescent chemosensors based on catechol and 8-Hydroxyquinoline chromophores, and their complexes with group 13 metal ions. Inorg. Chem. Commun., 2011, 14, 831-835.
Rifat, A.; Minati, B.; Kanungo, B.K. Design, synthesis and photophysical properties of 8-hydroxyquinoline-functionalized tripodal molecular switch as a highly selective sequential pH sensor in aqueous solution. RSC Advances, 2015, 21, 16207-16222.
Urano, Y.; Kamiya, M.; Kanda, T.; Ueno, T.; Hirose, K.; Nagano, T. Evolution of fluorescein as a platform for finely tunable fluorescence probes. J. Am. Chem. Soc., 2005, 127, 4888-4894.
Ozbek, N.; Kavak, G.; Ozcan, Y.; Ide, S.; Karacan, N. Structure, antibacterial activity and theoretical study of 2-hydroxy-1-naphthaldehyde-N-methylethanesulfonylhydrazone. J. Mol. Struct., 2009, 919, 154-159.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [620 - 630]
Pages: 11
DOI: 10.2174/1573411015666190314154126
Price: $65

Article Metrics

PDF: 11