Mitochondria-targeted acridine-based dual-channel fluorescence chemosensor for detection of Sn4+ and Cr2O72- ions in water and its application in discriminative detection of cancer cells
Graphical Abstract
Introduction
In recent times, because of the rapid development of bulk scale industries, larger amounts of organic and inorganic metal ions have been discharged into the environment, posing serious health risks to humans and aquatic systems (Zhou et al., 2014, Kim et al., 2012, Zhang et al., 2014, Hu et al., 2021, Juvekar et al., 2021). Among them, tetravalent tin, Sn(IV), is a significant trace element involved in numerous biochemical processes in humans and animals (Snoeij et al., 1987). Higher levels of Sn(IV) can be found in the liver, spleen, and adrenal and thyroid glands (Cardarelli, 1990, Sherman et al., 1986, Florea and Büsselberg, 2006). At minimal levels, Sn(IV) is constructive for body growth, protein and nucleic acid synthesis, regulation of homeostasis, and the inhibition of cancer cell development (Cheng et al., 2015, Mahapatra et al., 2013). The deficiency of Sn(IV), however, has been shown to be a risk factor for the loss of hearing, poor muscle growth, and limited cancer prevention (Brulíkova et al., 2020). On the other hand, toxicological research in humans and animals shows that surplus accumulation of Sn(IV) can have heavy neurotoxic and immunotoxic effects with the symptoms of gastrointestinal disease. Other severe problems also associated with excessive Sn(IV) include skin and eye irritation, breathing trouble, headaches, urinary tract infections, and damage to the liver, immune system, and chromosome (Mahapatra et al., 2014b). According to the World Health Organization (WHO) guidelines, the permissible concentrations of tin in packed foods and drinking water are 2.105 × 10-6 M and from 8.4 × 10-4 to 8.4 × 10-3 M, respectively (Wang et al., 2015).
Hexavalent chromium, available in the form of water-soluble dichromate (Cr2O72-) anions, confers adverse effects similar to those of Sn(IV) ions. Recent studies have focused on the specific detection of Cr2O72- ions. The Cr2O72- ions are well studied for their carcinogenic, toxic, and noxious effects on humans (Mohandoss et al., 2016). Even at low concentrations, Cr2O72- can induce severe health problems such as pulmonary sensitivity and skin, dental, respiratory tract, and renal damage (Zhu et al., 2021, Zhang et al., 2020). Because of its hazardous nature, the United States Environmental Protection Agency (USEPA) has declared Cr2O72- an extremely toxic ion, and the WHO set the threshold limit for Cr2O72- in drinking water as 9.6 × 10-7 M (WHO, 1997). Thus, because of its significant negative impacts, new or improved methods for rapid and selective dichromate ion detection at micromolar or submicromolar levels remain a significant priority.
In modern industries, Sn is the main ingredient in the manufacturing of fertilizers and paints, and in electrochemical industries, Cr is mainly used in the electroplating process. Because of the large deposition of these ions in the environment, Sn and Cr ions can persist for a prolonged period of time and are not fully decomposable. The environmental accumulation of these ions over many years has negatively impacted aquatic microorganisms. Sn and Cr pollution has led to toxicological effects on fungi, phytoplankton, and algae (Wei et al., 2015). Phytoplankton are significantly involved in the delivery process of oxygen to other water microorganisms and help to maintain the food chain to support other aquatic living organisms (Adhikari et al., 2016). Thus, Sn and Cr ion pollution hinder the infiltration of sunlight into water, which leads to destructive effects on aquatic living systems. Also, Sn and Cr ions enact numerous health effects on humans. Sn and Cr ions weakly participate in hydrogen bonding, conferring some biological solubility that allows entry into the human body through the skin and the digestive and respiratory tracts. Thus, the accumulation of these ions can create short-term effects, such as dyspnea, heavy perspiration, eye exasperations, and urinary tract infections, and permanent health issues, such as liver damage, immune disorders, up normal progress in DNA (Rüdel, 2003), in humans. Thus, there is a strong need for the biological and ecological analysis of Sn and Cr ions.
Numerous analytical techniques have been reported for the sensitive, selective, and rapid recognition of toxic metals and anions at trace levels (Wu et al., 2020, Bose et al., 2021, Mukherjee et al., 2020, Subramanian et al., 2020). Nevertheless, these analytical techniques suffer from several practical demerits such as the requirement of sophisticated instruments, difficult procedures for sample preparation, time-consuming processes, and the need for well-trained technicians (Qin et al., 2020, Ravichandiran et al., 2021b). Efficient techniques should therefore be developed to facilitate rapid detection, offer ease of operation, and increase economic feasibility. Optical sensors attract wide attention among researchers for their practical advantages of being simple to operate, highly portable, independent of sophisticated instrumental facilities, and relatively low cost (Wei et al., 2020). Among various optical sensors, fluorescence chemosensors are one of the most authoritative detection methods, and traces of analytes can be determined based on fluorescence enhancement and quenching responses (Ye et al., 2015, Hosseini et al., 2012). These investigations indicate that the use of fluorescence chemosensors is appropriate for the recognition and the qualitative and quantitative determination of toxic analytes, sidestepping the need for expensive analytical instruments while supplying precise real-time detection.
Optical chemosensors consist of three structural components: binding, receptor, and signaling moieties. The three structural units are neither covalently nor non-covalently bonded. The most commonly used binding groups are thiourea, urea, amide, pyrazole, benzoxazole, and pyrrole, which can be interrelated to the specific target through the establishment of hydrogen bonds that communicate these interactions through their translation into electrical output (Kannan and Veeraragavan, 2021, Montis et al., 2019). Moreover, due to the excellent fluorescence behavior of acridine-based molecules, chemosensors can offer utility for the detection of selective analytes. A few acridine derivatives have been employed to track accretion, the cellular location of drug hybrids, and intracellular pH (Stocks et al., 2007). Recently, the theoretical and experimental photophysical behavior of acridine derivatives has been extensively investigated (Hoshino et al., 2012, Fukuzumi, 2008). Especially, 9-amino aryl-substituted acridine derivatives have attracted much interest due to their excellent photoexcitation properties that result in intramolecular charge transfer (Grabowski et al., 2003). Besides, acridine derivatives exhibit good biological activity including antiviral, antimalarial, antimicrobial, leishmanicidal, antitrypanosomal, anticancer, and anti-prion properties (Sasvari et al., 2009, Di Giorgio et al., 2007, Gensicka-Kowalewska et al., 2017). Hence, the acridine core has been utilized in many fields that touch upon analyte detection, which shows the expediency of this core in biomedical and environmental research.
Several fluorescence chemical sensing probes are available to detect Sn4+ and Cr2O72- ions. Brulíkova et al. reported the bis-rhodamine-based chemosensor for Sn4+ ions in Britton-Robinson buffer (Brulíkova et al., 2020). Wang et al. (2019) prepared a silole-rhodamine chemosensor to detect Sn4+ through the dark resonance energy transfer mechanism. Mahapatra et al. (2014b) reported the synthesis of a pyrene thiazole conjugate for the recognition of Sn4+ ions, and the probe was utilized for bioimaging of live cells. The same researchers reported the rhodamine-based chemosensor for Sn4+ detection (Mahapatra et al., 2013). Recently, Zhou et al. (2019) described the preparation of two-dimensional polymers for the selective detection of CrO42- ions in water. Very recently, Qin et al. (2021) reported a metal-organic framework (MOF) for the multi-analyte detection of Fe3+, CrO42-, and Cr2O72- ions in an aqueous solution. Similarly, Fan et al. (2018) reported the preparation of a MOF as a multi-response chemosensor for Fe3+, Cr2O72-, and ATP2- ions in aqueous media. Recently, Xu et al. (2020) described the synthesis of cucurbit[8]uril- (Q[8]) and acridine hydrochloride-based chemosensors for amino acid recognition. Later, Fabiane et al. reported the synthesis of a novel macrocycle acridine-based chemosensor to detect Cd2+ ions (dos Santos Carlos et al., 2020). Wang et al. (2018) reported the preparation of acridine-based chemosensors for the simultaneous detection of Fe3+ and Ni2+ ions. Yoon et al. described the synthesis of a new imidazolium acridine derivative to detect H2PO4- ions (Kim et al., 2008). Lee et al. (2008) reported the preparation of acridine derivatives with immobilized azacrown ligands to recognize Hg2+ and Cd2+ ions in buffered DMSO solution. Nevertheless, most of these reported chemosensors are either restricted by the interference of background fluorescence, subject to generic quenching by competitive ions, or otherwise suffer from poor water compatibility and are impractical for bioimaging applications.
The construction of water-compatible chemosensors is a critical prerequisite for their utilization in a wide variety of environmental and biological applications. In our earlier reports, we developed a series of chemosensors beneficial to detect Sn2+ ions in a buffered aqueous medium and in biological samples (Ravichandiran et al., 2021b, Ravichandiran et al., 2020b, Ravichandiran et al., 2021a). To adapt our previous work to a sensor useful for tin and dichromate detection in biological applications, herein, we report the synthesis of new mitochondria-targeted N-(acridin-9-yl)-2,2-diphenylacetamide (NDA) chemosensor for the dual-channel fluorescence detection of Sn4+ and Cr2O72- ions in water. The NDA chemosensor showed excellent performance in water with high selectivity and sensitivity with the limit of detection (LOD) 0.268 μM and 0.160 μM for Sn4+ and Cr2O72-, respectively. The interference from other metal ions, amino acids, and peptides was mitigated by NDA. The proposed sensing mechanism was carefully described by FT-IR NMR, and mass analyses. Further, the sensing mechanism was additionally supported by theoretical calculations (DFT). Fascinatingly, the chemosensor NDA showed discriminative identification of Sn4+ in human cancer cells compared to normal live cells. Additionally, the mitochondria-targeting capacity of NDA was demonstrated in human cancer cells (FaDu).
Section snippets
Preparation of the NDA chemosensor
The NDA chemosensor was synthesized according to the procedure reported in Scheme 1. The detailed synthetic procedure and details regarding the structural characterization of NDA are presented in the Supporting Information Section (SI, Figs. S1 and S2).
Stock solution preparation of NDA and analytes
Unless otherwise specified, water was used as a working solvent medium for UV/vis and fluorescence emission studies. NDA was prepared at 2 mM in acetonitrile (CH3CN). All the metal ions, amino acids, and peptides were prepared at 100 mM in
Design and preparation of the NDA chemosensor
According to Pearson’s hard and soft acid-base theory, Sn4+ is a marginal soft acid possessing a strong electrophilic character. Hence, it establishes coordination bonds with electronegative soft bases such as nitrogen and oxygen (Su et al., 2016, Pearson, 1963). With regard to the main characteristic features of Sn4+, the NDA chemosensor was rationally designed and synthesized to consist of electronegative nitrogen and oxygen atoms. Starting materials, 9-aminoacridine hydrochloride monohydrate
Conclusions
A cheap, economically viable, and easy to prepare new dual-channel fluorescence chemosensor NDA based on acridine-diphenylacetyl units was designed and synthesized. The NDA works as a highly selective dual-detection probe for Sn4+ and Cr2O72- ions through the fluorescence “off-on-off” mode in water. The chemosensor NDA showed exceptional analytical performance with regards to water suitability, quick response, and selectivity and sensitivity towards Sn4+ and Cr2O72- ions. The mechanism of NDA
CRediT authorship contribution statement
Palanisamy Ravichandiran: Designed experiments, collected/analyzed data, and wrote the complete draft of the manuscript. D. S. Prabakaran: Carried out experimental work in bioimaging of live cells. Nikhil Maroli: Carried out DFT investigation. Ae Rhan Kim: Data analysis, Review and instruments support. Byung-Hyun Park: Project administration. Myung-Kwan Han: Project administration. Samuel Ponpandian: Collaborative support. Thiyagarajan Ramesh: Collaborative support. Dong Jin Yoo: Review,
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was supported by grants from the Medical Research Center Program (NRF-2017R1A5A2015061) through the National Research Foundation (NRF), which is funded by the Korean government (MSIP). This research was also funded by Korea Institute of Energy Technology Evaluation and Planning (KETEP) and the Ministry of Trade, Industry & Energy (MOTIE) of the Republic of Korea (No. 20184030202210).
References (77)
- et al.
Isomorphic Cd(II)/Zn(II)-MOFs as bifunctional chemosensors for anion (Cr2O72−) and cation (Fe3+) detection in aqueous solution
Inorg. Chem. Commun.
(2020) - et al.
Two rhodamine based chemosensors for Sn4+ and the application in living cells
Sens. Actuators B Chem.
(2015) - et al.
A conformational transition based fluorescent probe for mapping lysosomal viscosity fluctuations by fluorescence lifetime imaging
Sens. Actuators B Chem.
(2021) - et al.
Synthesis and antileishmanial activity of 6-mono-substituted and 3,6-di-substituted acridines obtained by acylation of proflavine
Eur. J. Med. Chem.
(2007) - et al.
A novel macrocycle acridine-based fluorescent chemosensor for selective detection of Cd2+ in Brazilian sugarcane spirit and tobacco cigarette smoke extract
Inorg. Chim. Acta
(2020) Identification and structure elucidation by NMR spectroscopy
TrAC Trends Anal. Chem.
(2015)- et al.
A novel dichromate-sensitive fluorescent nano-chemosensor using new functionalized SBA-15
Anal. Chim. Acta
(2012) - et al.
Three multifunctional coordination polymers based on the amide-functionalized N2,N5-di(pyridin-3-yl)thiophene-2,5-dicarboxamide ligand (Nptp): synthesis, magnetic properties and luminescent sensing for Pb2+, Cr2O72− and acetone
Polyhedron
(2020) - et al.
Recent progress in the two-photon fluorescent probes for metal ions
Coord. Chem. Rev.
(2021) - et al.
Synthesis, characterization of vanillin based colorimetric chemosensor for sensing of fluoride ions
J. Mol. Struct.
(2021)
A new imidazolium acridine derivative as fluorescent chemosensor for pyrophosphate and dihydrogen phosphate
Tetrahedron
New acridine derivatives bearing immobilized azacrown or azathiacrown ligand as fluorescent chemosensors for Hg2+ and Cd2+
Tetrahedron Lett.
Architecture of multi-channel and easy-to-make sensors for selective and sensitive Hg2+ ion recognition through Hg-C and Hg-N bonds of naphthoquinone-aniline/pyrene union
J. Hazard. Mater.
Host-guest molecular recognition based fluorescence On-Off-On chemosensor for nanomolar level detection of Cu2+ and Cr2O72− ions: application in XNOR logic gate and human lung cancer living cell imaging
Sens. Actuators B Chem.
A vibrational spectral maker for probing the hydrogen-bonding status of protonated asp and glu residues
Biophys. J.
Turn-on fluorescence study of a highly selective acridine-based chemosensor for Zn2+ in aqueous solutions
Inorg. Chim. Acta
A stable multifunctional cadmium-organic framework based on 2D stacked layers: effective gas adsorption, and excellent detection of Cr3+, CrO42−, and Cr2O72-
Dyes Pigments
A phenoxazine-based fluorescent chemosensor for dual channel detection of Cd2+ and CN− ions and its application to bio-imaging in live cells and zebrafish
Dyes Pigments
Mitochondria-targeted dual-channel colorimetric and fluorescence chemosensor for detection of Sn2+ ions in aqueous solution based on aggregation-induced emission and its bioimaging applications
J. Hazard. Mater.
Case study: bioavailability of tin and tin compounds
Ecotoxicol. Environ. Saf.
Small in size but mighty in force” – the first principle study of the impact of A/D units in A/D-phenyl-π-phenothiazine-π-dicyanovinyl systems on photophysical and optoelectronic properties
Dyes Pigments
Biological activity of organotin compounds—an overview
Environ. Res.
A simple fluorescence turn-on chemosensor based on Schiff-base for Hg2+-selective detection
Tetrahedron Lett.
Enhancing the sensitivity of point-of-use electrochemical microfluidic sensors by ion concentration polarisation – a case study on arsenic
Sens. Actuators B Chem.
Novel rhodamine based chemosensor for detection of Hg2+: Nanomolar detection, real water sample analysis, and intracellular cell imaging
Sens. Actuators B Chem.
Construction of a mitochondria-targeted ratiometric fluorescent probe for monitoring hydrazine in soil samples and culture cells
J. Hazard. Mater.
Acridine-based fluorescence chemosensors for selective sensing of Fe3+ and Ni2+ ions
Spectrochim. Acta Part A
Highly sensitive and selective fluorescent detection of rare earth metal Sn(II) ion by organic fluorine Schiff base functionalized periodic mesoporous material in aqueous solution
J. Photochem. Photobiol. A
Four luminescent metal-organic chain compounds based on semi-rigid N-donor ligands and 3-hydroxy-2-naphthoic acid for recognition of Fe3+ and Cr2O72− ions
Polyhedron
A multi-state fluorescence switch based on a new photochromic diarylethene with a di-(ethyl-1,8-naphthalimidyl)amine unit
J. Photochem. Photobiol. A
Multi-mode fluorescence sensing detection based on one core-shell structure quantum dots via different types of mechanisms
Spectrochim. Acta Part A Mol. Biomol. Spectrosc.
Sensors for in situ real-time fluorescence imaging of enzymes
Chem
Amino acid recognition by a fluorescent chemosensor based on cucurbit[8]uril and acridine hydrochloride
Anal. Chim. Acta
A fluorescent zinc–pamoate coordination polymer for highly selective sensing of 2,4,6-trinitrophenol and Cu2+ ion
Sens. Actuators B Chem.
Ultrasensitive detection of Cr(VI) (Cr2O72−/CrO42−) ions in water environment with a fluorescent sensor based on metal-organic frameworks combined with sulfur quantum dots
Anal. Chim. Acta
Multi-responsive luminescent sensors of two water-stable polynuclear Cd organic frameworks: synthesis, structures and sensing of tetracycline, Cr2O72− and Fe3+ ions in water
Microchem. J.
A through bond energy transfer based ratiometric probe for fluorescent imaging of Sn2+ ions in living cells
RSC Adv.
An efficient water-soluble fluorescent chemosensor based on furan Schiff base functionalized PEG for the sensitive detection of Al3+ in pure aqueous solution
New J. Chem.
Cited by (36)
Recent advances and challenges in monitoring chromium ions using fluorescent probes
2024, Coordination Chemistry ReviewsTriazole tethered organosilane based fluorescent sensor as a logic gate operation for selective detection of Sn<sup>2+</sup> ions: A potent Cyclooxygenase-2 inhibitor
2024, Journal of Photochemistry and Photobiology A: ChemistrySelective fluorescence turn-off detection of lysine by a curcumin derivative with real sample analysis
2023, Journal of Photochemistry and Photobiology A: ChemistryRecent developments in the preparation, characterization, and applications of chemosensors for environmental pollutants detection
2023, Journal of Environmental Chemical EngineeringBF<inf>3</inf> detection by pyrazolo-pyridine based fluorescent probe and applications in bioimaging and paper strip analysis
2023, Journal of Molecular Liquids