Complexation of 1,3-dihetaryl-5-phenyl-2-pyrazoline Derivatives with Polyvalent Metal Ions: Quantum Chemical Modeling and Experimental Investigation


  • Andrii Chumak V. N. Karazin Kharkiv National University
  • Ruslana Khodzhaeva V. N. Karazin Kharkiv National University
  • Olena Kharchenko V. N. Karazin Kharkiv National University
  • Volodymyr Kotlyar V. N. Karazin Kharkiv National University
  • Oleksii Kolomoitsev V. N. Karazin Kharkiv National University
  • Andrii Doroshenko V. N. Karazin Kharkiv National University



1,3,5-triaryl-2-pyrazoline, pyridine, benzimidazole, spectrophotometric and fluorescence analysis, complexation, polyvalent metal ions, quantum-chemical calculations, benzothiazole, Bader's atoms-in-molecules (AIM) theory


1,3,5-Triaryl-2-pyrazoline derivatives with a pyridine ring in position 1 and 2-benzimidazolyl or 2-benzothiazolyl bicycles in position 3 were synthesized. Spectral properties in solvents of similar polarity, i.e. aprotic acetonitrile and in protic methanol, were studied, complexation with cadmium and mercury ions in acetonitrile was elucidated as well. Quantum-chemical modeling with application of the elements of Bader's atoms-in-molecules (AIM) theory of the title molecules conformational structure and 1:1 stoichiometry complexes formed with polyvalent metals of various nature (Mg, Zn, Cd, Pb, Hg, Ba) was conducted. The principal possibility of “nitrogen-sulfur” switching of the metal ions binding sites for the benzothiazole derivative was revealed, and makes possible to classify this compound as “smart ligand”.


Nolan E, Lippard S. Small-Molecule Fluorescent Sensors for Investigating Zinc Metalloneurochemistry. Accounts of Chemical Research 2008;42(1):193-203.

Wu J, Liu W, Ge J, Zhang H, Wang P. New sensing mechanisms for design of fluorescent chemosensors emerging in recent years. Chemical Society Reviews 2011;40(7):3483.

Li M, Gou H, Al-Ogaidi I, Wu N. Nanostructured Sensors for Detection of Heavy Metals: A Review. ACS Sustainable Chemistry & Engineering 2013;1(7):713-723.

Carter K, Young A, Palmer A. Fluorescent Sensors for Measuring Metal Ions in Living Systems. Chemical Reviews 2014;114(8):4564-4601.

Chowdhury S, Rooj B, Dutta A, Mandal U. Review on Recent Advances in Metal Ions Sensing Using Different Fluorescent Probes. Journal of Fluorescence 2018;28(4):999-1021.

Patil N, Dhake R, Ahamed M, Fegade U. A Mini Review on Organic Chemosensors for Cation Recognition (2013-19). Journal of Fluorescence 2020;30(6):1295-1330.

Shao N, Gao X, Wang H, Yang R, Chan W. Spiropyran-based optical approaches for mercury ion sensing: Improving sensitivity and selectivity via cooperative ligation interactions using cysteine. Analytica Chimica Acta 2009;655(1-2):1-7.

Baldrighi M, Locatelli G, Desper J, Aakeröy C, Giordani S. Probing Metal Ion Complexation of Ligands with Multiple Metal Binding Sites: The Case of Spiropyrans. Chemistry - A European Journal 2016;22(39):13976-13984.

Eshtiagh-Hosseini H, Aghabozorg H, Mirzaei M, Amini M, Chen Y, Shokrollahi A, Aghaei R. Diversity in coordination behavior of dipicolinic acid with lead(II), calcium(II), and nickel(II) in the presence of pyrazine and 2-amino-4-methylpyridine spacers in construction of three supramolecular architectures. Journal of Molecular Structure 2010;973(1-3):180-189.

Koner R, Sinha S, Kumar S, Nandi C, Ghosh S. 2-Aminopyridine derivative as fluorescence ‘On–Off’ molecular switch for selective detection of Fe3+/Hg2+. Tetrahedron Letters 2012;53(18):2302-2307.

Mandal S, Ghosh S, Banerjee C, Kuchlyan J, Sarkar N. Unique Photophysical Behavior of 2,2′-Bipyridine-3,3′-diol in DMSO–Water Binary Mixtures: Potential Application for Fluorescence Sensing of Zn2+ Based on the Inhibition of Excited-State Intramolecular Double Proton Transfer. The Journal of Physical Chemistry B 2013;117(40):12212-12223.

Vosough Razavi B, Badiei A, Lashgari N, Mohammadi Ziarani G. 2,6-Bis(2-Benzimidazolyl)Pyridine Fluorescent Red-Shifted Sensor for Recognition of Zinc(II) and a Calorimetric Sensor for Iron Ions. Journal of Fluorescence 2016;26(5):1723-1728.

Ruan Y, Xie J. Unexpected highly selective fluorescence ‘turn-on’ and ratiometric detection of Hg2+ based on fluorescein platform. Tetrahedron 2011;67(45):8717-8723.

Yang X, Li Y, Bai Q. A highly selective and sensitive fluorescein-based chemodosimeter for Hg2+ ions in aqueous media. Analytica Chimica Acta 2007;584(1):95-100.

Chen J, Zheng A, Chen A, Gao Y, He C, Kai X, Wu G, Chen Y. A functionalized gold nanoparticles and Rhodamine 6G based fluorescent sensor for high sensitive and selective detection of mercury(II) in environmental water samples. Analytica Chimica Acta 2007;599(1):134-142.

Huang J, Xu Y, Qian X. A Rhodamine-Based Hg2+ Sensor with High Selectivity and Sensitivity in Aqueous Solution: A NS2- Containing Receptor. The Journal of Organic Chemistry 2009;74(5):2167-2170.

Mao J, He Q, Liu W. An rhodamine-based fluorescence probe for iron(III) ion determination in aqueous solution. Talanta 2010;80(5):2093-2098.

Kumar M, Kumar N, Bhalla V. Rhodamine appended thiacalix[4]arene of 1,3-alternate conformation for nanomolar detection of Hg2+ ions. Sensors and Actuators B: Chemical 2012;161(1):311-316.

Ling L, Zhao Y, Du J, Xiao D. An optical sensor for mercuric ion based on immobilization of Rhodamine B derivative in PVC membrane. Talanta 2012;91:65-71.

Wang F, Nam S, Guo Z, Park S, Yoon J. A new rhodamine derivative bearing benzothiazole and thiocarbonyl moieties as a highly selective fluorescent and colorimetric chemodosimeter for Hg2+. Sensors and Actuators B: Chemical 2012;161(1):948-953.

Kuchlyan J, Basak S, Dutta D, Das A, Mal D, Sarkar N. A new rhodamine derived fluorescent sensor: Detection of Hg2+ at cellular level. Chemical Physics Letters 2017;673:84-88.

Wan J, Zhang K, Li C, Li Y, Niu S. A novel fluorescent chemosensor based on a rhodamine 6G derivative for the detection of Pb2+ ion. Sensors and Actuators B: Chemical 2017;246:696-702.

Carturan S, Quaranta A, Maggioni G, Bonafini M, Della Mea G. 3-Hydroxyflavone-based wavelength shifting systems for near UV optical sensors. Sensors and Actuators A: Physical 2004;113(3):288-292.

de la Rosa-Romo L, Oropeza-Guzmán M, Olivas-Sarabia A, Pina-Luis G. Flavone functionalized magnetic nanoparticles: A new fluorescent sensor for Cu2+ ions with nanomolar detection limit. Sensors and Actuators B: Chemical 2016;233:459-468.

Gao H, Wu X. A 3-hydroxyflavone derivative as fluorescence chemosensor for copper and zinc ions. Chemistry of Heterocyclic Compounds 2018;54(2):125-129.

Yang S, Hu Z, Guo D. Novel flavonoid derivatives and their corresponding rare earth complexes: Synthesis and luminescent properties. Journal of Luminescence 2021;237:118195.

Michalík M, Biela M, Cagardová D, Lukeš V. Chelates of 3- and 5-hydroxyflavone: Quantum chemical study. Chemical Physics Letters 2021;762:138142.

Kamecki F, Marcucci C, Ferreira-Gomes M, Sabatier L, Knez D, Gobec S, Monti J, Rademacher M, Marcos A, de Tezanos Pinto F, Gavernet L, Colettis N, Marder M. 2’-Hydroxy-4’,5’-dimethyl-4-dimethylaminochalcone, a novel fluorescent flavonoid with capacity to detect aluminium in cells and modulate Alzheimer’s disease targets. Journal of Photochemistry and Photobiology A: Chemistry 2021;409:113137.

Qin T, Liu B, Xu Z, Yao G, Xu H, Zhao C. Flavonol-based small-molecule fluorescent probes. Sensors and Actuators B: Chemical 2021;336:129718.

Drabovich A, Berezovski M, Musheev M, Krylov S. Selection of Smart Small-Molecule Ligands: The Proof of Principle. Analytical Chemistry 2008;81(1):490-494.

Dondaine L, Escudero D, Ali M, Richard P, Denat F, Bettaieb A, Le Gendre P, Paul C, Jacquemin D, Goze C, Bodio E. Coumarin‐Phosphine‐Based Smart Probes for Tracking Biologically Relevant Metal Complexes: From Theoretical to Biological Investigations. European Journal of Inorganic Chemistry 2016;2016(4):545-553.

Banerjee M, Ghosh M, Ta S, Das J, Das D. A smart optical probe for detection and discrimination of Zn2+, Cd2+ and Hg2+ at nano-molar level in real samples. Journal of Photochemistry and Photobiology A: Chemistry 2019;377:286-297.

Chumak AY, Kordubailo MV, Vodolazhenko MA, Kotliar VM, Doroshenko AO. Derivatives of 1,3,5 triaryl-2-pyrazoline with additional heterocyclic moieties in position 1 as potential fluorescent chemosensing compounds for detection of polyvalent metals cations. Kharkiv University Bulletin Chemical Series. 2018;31(54):32-43.

Melhuish W. Absolute spectrofluorometry. Journal of Research of the National Bureau of Standards Section A: Physics and Chemistry 1972;76A(6):547.

Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 09, Revision B.01. Wallingford CT: Gaussian, Inc.; 2010.

Zhao Y, Schultz N, Truhlar D. Design of Density Functionals by Combining the Method of Constraint Satisfaction with Parametrization for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions. Journal of Chemical Theory and Computation 2006;2(2):364-382.

Woon D, Dunning T. Gaussian basis sets for use in correlated molecular calculations. III. The atoms aluminum through argon. The Journal of Chemical Physics 1993;98(2):1358-1371.

Canal Neto A, Muniz E, Centoducatte R, Jorge F. Gaussian basis sets for correlated wave functions. Hydrogen, helium, first- and second-row atoms. Journal of Molecular Structure: THEOCHEM 2005;718(1-3):219-224.

de Oliveira P, Barros C, Jorge F, Canal Neto A, Campos M. Augmented Gaussian basis set of double zeta valence quality for the atoms Rb and Y–Xe: Application in DFT calculations of molecular electric properties. Journal of Molecular Structure: THEOCHEM 2010;948(1-3):43-46.

Bader R. Atoms in molecules. Accounts of Chemical Research 1985;18(1):9-15.

Bader R. A quantum theory of molecular structure and its applications. Chemical Reviews 1991;91(5):893-928.

Bader R. A Bond Path: A Universal Indicator of Bonded Interactions. The Journal of Physical Chemistry A 1998;102(37):7314-7323.

Biegler-König F, Schönbohm J, Bayles D. AIM2000 - A Program to Analyze and Visualize Atoms in Molecules. Journal of Computational Chemistry. 2001;22(5):545-59.<545::aid-jcc1027>;2-y

Dunning TH, Hay PJ. Gaussian Basis Sets for Molecular Calculations. In: Schaefer HF, editor. Methods of Electronic Structure Theory. Boston, MA: Springer US; 1977. p. 1-27.

Espinosa E, Molins E, Lecomte C. Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities. Chemical Physics Letters 1998;285(3-4):170-173.

Zhikol O, Shishkin O. Estimating stacking interaction energy using atom in molecules properties: Homodimers of benzene and pyridine. International Journal of Quantum Chemistry 2012;112(18):3008-3017.

Shannon R. Revised effective ionic radii and systematic studies of interatomic distances in halides and chalcogenides. Acta Crystallographica Section A 1976;32(5):751-767.

Peng C, Ayala P, Schlegel H, Frisch M. Using redundant internal coordinates to optimize equilibrium geometries and transition states. Journal of Computational Chemistry 1996;17(1):49-56.<49::aid-jcc5>;2-0

Doroshenko A, Skripkina V, Schershukov V, Ponomaryov O. Fluorescence quenching in bichromophoric systems with nonconjugated chromophores: 5-substituted derivatives of l,3,5-triaryl-2-pyrazoline. Journal of Fluorescence 1997;7(2):131-138.

Krasovitskii B, Pereyaslova D, Skripkina V, Yagupolskii L, Popov V. Organic luminophores with fluorine-containing substituents. Dyes and Pigments 1988;9(1):21-35.

Letrun R, Lang B, Yushchenko O, Wilcken R, Svechkarev D, Kolodieznyi D, Riedle E, Vauthey E. Excited-state dynamics of a molecular dyad with two orthogonally-oriented fluorophores. Physical Chemistry Chemical Physics 2018;20(48):30219-30230.

Ermolaev V, Sveshnikova E. Limits to the applicability of the rule of equality to unity of the sum of quantum yields of fluorescence and transition to the triplet state for complex organic molecules in the condensed phase (A review). Optics and Spectroscopy 2015;119(4):642-655.

Plotnikov V. Regularities of the processes of radiationless conversion in polyatomic molecules. International Journal of Quantum Chemistry 1979;16(3):527-541.

Plotnikov V. Theoretical Foundations of the Classification of Molecules by Luminescence Spectra. Russian Chemical Reviews 1980;49(2):172-189.

Lippert E, Rettig W, Bonacic-Koutecky V, Heisel F, Miehe JA. Photophysics of internal twisting. In: Prigogine I, Rice SA, editors. Advances in Chemical physics. 68. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 1987. p. 1-174.

Grabowski Z, Rotkiewicz K, Rettig W. Structural Changes Accompanying Intramolecular Electron Transfer: Focus on Twisted Intramolecular Charge-Transfer States and Structures. Chemical Reviews 2003;103(10):3899-4032.

Doroshenko A, Kirichenko A, Mitina V, Ponomaryov O. Spectral properties and dynamics of the excited state structural relaxation of the ortho analogues of POPOP — Effective abnormally large Stokes shift luminophores. Journal of Photochemistry and Photobiology A: Chemistry 1996;94(1):15-26.

Iliashenko R, Zozulia O, Doroshenko A. High Stokes shift long-wavelength energy gap regulated fluorescence in the series of nitro/dimethylamino-substituted ortho-analogs of POPOP. Open Chemistry 2011;9(6):962-971.

Demchenko A. The problem of self-calibration of fluorescence signal in microscale sensor systems. Lab on a Chip 2005;5(11):1210.

Demchenko A. The Concept of λ-Ratiometry in Fluorescence Sensing and Imaging. Journal of Fluorescence 2010;20(5):1099-1128.

Demchenko A. Practical aspects of wavelength ratiometry in the studies of intermolecular interactions. Journal of Molecular Structure 2014;1077:51-67.

Nolan E, Lippard S. Tools and Tactics for the Optical Detection of Mercuric Ion. Chemical Reviews 2008;108(9):3443-3480.

Callan J, de Silva A, Magri D. Luminescent sensors and switches in the early 21st century. Tetrahedron 2005;61(36):8551-8588.

Ellairaja S, Manikandan R, Vijayan M, Rajagopal S, Vasantha V. A simple highly sensitive and selective TURN-ON fluorescent chemosensor for the detection of cadmium ions in physiological conditions. RSC Advances 2015;5(78):63287-63295.

Ma J, Dong Y, Yu Z, Wu Y, Zhao Z. A pyridine based Schiff base as a selective and sensitive fluorescent probe for cadmium ions with “turn-on” fluorescence responses. New Journal of Chemistry 2022;46(7):3348-3357.

Li M, Lu H, Liu R, Chen J, Chen C. Turn-On Fluorescent Sensor for Selective Detection of Zn2+, Cd2+, and Hg2+ in Water. The Journal of Organic Chemistry 2012;77(7):3670-3673.

Sharma P, Bhogal S, Lealam A, Kumar S, Yusuf M, Malik A. Experimental and Theoretical Studies of the Pyrazoline Derivative 5-(4-methylphenyl)-3-(5-methylfuran-2-yl)-1-phenyl-4,5-dihydro-1H-Pyrazole and its Application for Selective Detection of Cd2+ ion as Fluorescent Sensor. Journal of Fluorescence 2022;32(3):969-981.

Wang H, Wu S. Highly selective fluorescent sensors for mercury(II) ions and their applications in living cell imaging. Tetrahedron 2013;69(8):1965-1969.

Kao S, Wu S. A fluorescent turn-on probe for Hg(II) based on an NTe2 chelating motif and its application in living cell imaging. Sensors and Actuators B: Chemical 2015;212:382-388.

Vedamalai M, Wu S. A BODIPY-based colorimetric and fluorometric chemosensor for Hg(ii) ions and its application to living cell imaging. Organic & Biomolecular Chemistry 2012;10(28):5410.

Bozkurt E, Gul H. Selective fluorometric “Turn-off” sensing for Hg2+ with pyrazoline compound and its application in real water sample analysis. Inorganica Chimica Acta 2020;502:119288.

Saleem M, Khang C, kim M, Lee K. Chromo/Fluorogenic Detection of Co2+, Hg2+ and Cu2+ by the Simple Schiff Base Sensor. Journal of Fluorescence 2015;26(1):11-22.

Svechkarev D, Dereka B, Doroshenko A. Mercury Ions Complexation with a Series of Heterocyclic Derivatives of 3-Hydroxychromone: Spectral Effects and Prospects for Ultrasensitive Hg2+ Probing. The Journal of Physical Chemistry A 2011;115(17):4223-4230.

Gauthama B, Narayana B, Sarojini B, Suresh N, Sangappa Y, Kudva A, Satyanarayana G, Raghu S. Colorimetric “off–on” fluorescent probe for selective detection of toxic Hg2+ based on rhodamine and its application for in-vivo bioimaging. Microchemical Journal 2021;166:106233.