nanomaterials Article Mechanistic Insight of Sensing Hydrogen Phosphate in Aqueous Medium by Using Lanthanide(III)-Based Luminescent Probes Jashobanta Sahoo 1,2,3 , Santlal Jaiswar 4, Pabitra B. Chatterjee 2,5, Palani S. Subramanian 1,2,* and Himanshu Sekhar Jena 6,* 1 Inorganic Materials and Catalysis Division, Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar, Gujarat 364 002, India; [email protected] 2 Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar, Gujarat 364 002, India; [email protected] 3 Department of Chemistry, Hindol College, Khajuriakata, Higher Education Department, State Government of Odisha, Bhubaneswar, Odisha 751001, India 4 Discipline of Marine Biotechnology and Ecology, CSIR-CSMCRI, Bhavnagar, Gujarat 364 002, India; [email protected] 5 Analytical Discipline and Centralized Instrument Facility, CSIR-CSMCRI, Bhavnagar, Gujarat 364 002, India 6 Department of Chemistry, Ghent University, Krijgslaan 281-S3 B, 9000 Ghent, Belgium * Correspondence: [email protected] or [email protected] (P.S.S.); [email protected] or [email protected] (H.S.J.) Abstract: The development of synthetic lanthanide luminescent probes for selective sensing or binding anions in aqueous medium requires an understanding of how these anions interact with synthetic lanthanide probes. Synthetic lanthanide probes designed to differentiate anions in aqueous medium could underpin exciting new sensing tools for biomedical research and drug discovery. In this direction, we present three mononuclear lanthanide-based complexes, EuLCl3 (1), SmLCl3 (2), and TbLCl3 (3), incorporating a hexadentate aminomethylpiperidine-based nitrogen-rich heterocyclic ligand L for sensing anion and establishing mechanistic insight on their binding activities in aqueous Citation: Sahoo, J.; Jaiswar, S.; medium. All these complexes are meticulously studied for their preferential selectivities towards Chatterjee, P.B.; Subramanian, P.S.; different anions such as HPO 2−, SO 2−, CH COO−,I−, Br−, Cl−,F−, NO −, CO 2−/HCO −, Jena, H.S. Mechanistic Insight of 4 4 3 3 3 3 − Sensing Hydrogen Phosphate in and HSO4 at pH 7.4 in aqueous HEPES (2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid) 2− Aqueous Medium by Using buffer. Among the anions scanned, HPO4 showed an excellent luminescence change with all three 2− Lanthanide(III)-Based Luminescent complexes. Job’s plot and ESI-MS support the 1:2 association between the receptors and HPO4 . 2− Probes. Nanomaterials 2021, 11, 53. Systematic spectrophotometric titrations of 1–3 against HPO4 demonstrates that the emission 2− https://doi.org/10.3390/nano11010053 intensities of 1 and 2 were enhanced slightly upon the addition of HPO4 in the range 0.01–1 equiv and 0.01–2 equiv., respectively. Among the three complexes, complex 3 showed a steady quenching Received: 26 October 2020 of luminescence throughout the titration of hydrogen phosphate. The lower and higher detection Accepted: 23 December 2020 2− limits of HPO4 by complexes 1 and 2 were determined as 0.1–4 mM and 0.4–3.2 mM, respectively, Published: 28 December 2020 while complex 3 covered 0.2–100 µM. This concludes that all complexes demonstrated a high degree 2− of sensitivity and selectivity towards HPO4 . Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims Keywords: lanthanides; luminescence; nitrogen-rich ligand; phosphate sensing; quenching in published maps and institutional affiliations. 1. Introduction Copyright: © 2020 by the authors. Li- − Inorganic phosphates, the charged anions of phosphoric acid such as [H2PO4] , censee MDPI, Basel, Switzerland. This 2− 3− [HPO4] , and [PO4] , are essential components during the synthesis of DNA/RNA and article is an open access article distributed phospholipid membrane [1]. Further, their influence in the metabolic process in human, under the terms and conditions of the plant, and animal cells are inevitable. Sensing of phosphate draws special attention [2–13] Creative Commons Attribution (CC BY) due to its biological role as polyphosphate, and hyper- and hypophosphatemia in Chronic license (https://creativecommons.org/ Kidney Disease (CKD) patients [14]; energy source through dephosphorylation [15] of licenses/by/4.0/). Nanomaterials 2021, 11, 53. https://doi.org/10.3390/nano11010053 https://www.mdpi.com/journal/nanomaterials Nanomaterials 2021, 11, x FOR PEER REVIEW 2 of 14 Nanomaterials 2021, 11, 53 2 of 13 Kidney Disease (CKD) patients [14]; energy source through dephosphorylation [15] of ATP, ADP, AMP, and PPi; and reverse polycondensation to form polyphosphates. Vari- ATP,ous methods ADP, AMP, were and developed PPi; and reverse for the polycondensation determination of tophosphates form polyphosphates. in fertilizers, Various plants, methods were developed for the determination of phosphates in fertilizers, plants, natu- natural waters, and other environmental samples [16–18]. Generally, serum phosphates ral waters, and other environmental samples [16–18]. Generally, serum phosphates are are measured based on a photometric approach using ammonium phosphate, which measured based on a photometric approach using ammonium phosphate, which forms a forms a chromogenic complex with inorganic phosphates (Pi) [19]. However, the search chromogenic complex with inorganic phosphates (Pi) [19]. However, the search for new for new receptors with selective response to phosphates remains active behind many chal- receptors with selective response to phosphates remains active behind many challenges. lenges. Moreover, with phosphates being important bioanlytes [20–29], varieties of color- Moreover, with phosphates being important bioanlytes [20–29], varieties of colorimetric imetric sensors [30–35] and fluorosensors [36–38] were reported for their detection. sensors [30–35] and fluorosensors [36–38] were reported for their detection. Among these, Among these, luminescent lanthanide [20] complexes gained significant attention due to luminescent lanthanide [20] complexes gained significant attention due to their potential their potential applications in clinical diagnosis, biomarkers [39,40], MRI contrast agents applications in clinical diagnosis, biomarkers [39,40], MRI contrast agents [41–47], screen- [41–47], screening of drugs, etc. Parker et al. reported Eu(III) and Tb(III) tetra-aza- ing of drugs, etc. Parker et al. reported Eu(III) and Tb(III) tetra-azaphenylene complexes forphenylene the detection complexes of phosphates for the detection in live cells of phosph [48,49].ates It is in important live cells to [48,49]. note that It is the important concen- trationsto note that of phosphate the concentrations vary significantly of phosphate in inter- vary and significantly intracellular in environments inter- and intracellular of human cells,environments ranging fromof human 0.15 tocells, 1.3 ranging mM [50 –from52]. 0.15 Among to 1.3 the mM various [50–52]. lanthanide Among the complexes various reportedlanthanide so complexes far in the reported literature, so Eu-Tc far in [the53,54 literature,] was recognized Eu-Tc [53,54] as anwas efficient recognized probe as for an μ −1 phosphatesefficient probe due for to itsphosphates lower detection due to limitits lower (LOD detection = 3 µmolL limit−1). (LOD Moreover, = 3 molL there are). Moreo- many intracellularver, there are processes, many intracellular where the concentrationsprocesses, where of phosphate the concentrations vary among of differentphosphate subcel- vary lularamong compartments different subcellular present thereincompartments [55]. Therefore, present atherein highly [55]. sensitive Therefore, and selective a highly probesensi- whichtive and can selective detect phosphateprobe which at can a considerably detect phosphate low concentration at a considerably is very low much concentration required tois very investigate much required such intracellular to investigate processes. such intracellular In this context, processes. recently, In this we context, have reported recently, awe set have of europium(III) reported a set andof europi terbium(III)um(III) complexes,and terbium(III) incorporating complexes, different incorporating hexadentate differ- ligandsent hexadentate which showed ligands highly which selective showed andhighly efficient selective recognition and efficient of inorganic recognition phosphates of inor- andganic nucleoside phosphates phosphates and nucleoside [56,57]. phosphates In this direction [56,57]. and In asthis a partdirection of our and ongoing as a part research, of our herein,ongoing we research, report a herein, series ofwe relatively report a series simple, of cheap, relatively and simple, water-soluble cheap, and Ln(III) water-soluble complexes 1Ln(III), 2, and complexes3 (Scheme 1,) 2 (Ln, and = Eu,3 (Scheme Sm, and 1) Tb, (Ln respectively) = Eu, Sm, and using Tb,an respectively) aminomethylpiperidine- using an ami- functionalizednomethylpiperidine-functionalized 1,10-phenanthrolene-based 1,10-phenan nitrogenousthrolene-based heterocyclic nitrogenous ligand L asheterocyclic the metal chelator.ligand L Theas the anion-sensing metal chelator. ability The ofanion-sensing these hydrophilic ability rare-earth of these hydrophilic complexes (rare-earth1–3) was exploredcomplexes and (1 found–3) was high explored selectivity and and found sensitivity high selectivity for hydrogen and phosphatesensitivity ions for inhydrogen HEPES (2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonicphosphate ions in HEPES (2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic