5. Arsenic sensing

Considering the hazardous facts of arsenic, it is very important to detect arsenic both qualitatively and quantitatively. Many conventional methods like hydride generation atomic absorption spectrometry (HG-AAS), neutron activation analysis and X-ray analysis and stripping voltammetry are available to determine arsenic. Though these methods are available, they are not very cost-effective and are very complex [55–59]. To determine arsenic, easy and cost-effective methods are yet to be explored. In recent times various heavy metals and toxic anions are detected selectively and sensitively by using optical detection techniques (fluorescence and UV–Vis), which implement a viable and simple approach towards the detection process. Except optical (fluorescence and UV–Vis) detection methods, other available methods need complex experimental setup; hence, they are far from 'on-field' application purpose. Simplicity, low-cost and 'on-field' application possibilities make optical sensing technique versatile.

providing the second activation signal to the phosphorylated apoptosis signal-regulating kinase 1 (ASK1) protein, which then triggers the apoptotic pathway. As a result, unavailability of DAXX in the cytoplasm hinders the initiation of the apoptotic pathway. Under condition of excess oxidative stress, the SO3H form prevails which inactivates the protein and retranslocates back to the cytoplasm. As a result, the entire antioxidant response regulated by the activated DJ-1 protein is inhibited. Moreover, DAXX protein also becomes free, which then translocates into the cytoplasm and provides the required second activation signal to the

Arsenous acid [As(OH)3] formed by dissolving of arsenic trioxide (As2O3) was found to be an effective and safe treatment for acute promyelocytic leukemia (APL) in the 1970s. The United States Food and Drug Administration approved the use of As2O3 as a treatment for APL in September 2000 [50]. As2O3 treatment was shown to have a dual effect on APL cells, with low arsenic concentration (0.25–0.50 mM) favoring APL cell differentiation and high concentrations (1–2 mM) inducing apoptosis (programmed cell death). Direct arsenic binding to cysteine residues present in zinc fingers of promyelocytic leukemia fusion protein (PML-RARa) was found to be a mechanism underlying APL remission [51]. Arsenic binding induces a conformational change in the structure of the protein (PML-RARa), facilitating its oligomerization. This oligomerization enhances ubiquitylation and SUMOylation, resulting in its degradation [52]. Given the constant requirement for DNA and protein synthesis, thioredoxin (Trx) and thioredoxin reductase (TrxR) are observed to be overexpressed in various tumors. Moreover, in vivo data suggests that TrxR is necessary for the growth of tumor cells, making them

Arsenic has been proposed to induce cell death through thioredoxin reductase (TrxR) inhibition, with both N-terminal dithiols and C-terminal selenothiol interacting with arsenic compound [54]. Sensitivity of cells to arsenic can be attributed to high expression of membrane transporter aquaglyceroporin which allows arsenite uptake, along with a low, basal level of cellular glutathione. Multiple factors such as liver damage, cardiac toxicity and peripheral neuropathies caused by toxicity at higher dosage of As2O3, along with bioavailability of

Considering the hazardous facts of arsenic, it is very important to detect arsenic both qualitatively and quantitatively. Many conventional methods like hydride generation atomic absorption spectrometry (HG-AAS), neutron activation analysis and X-ray analysis and stripping voltammetry are available to determine arsenic. Though these methods are available, they are not very cost-effective and are very complex [55–59]. To determine arsenic, easy and cost-effective methods are yet to be explored. In recent times various heavy metals and toxic anions are detected selectively and sensitively by using optical detection techniques (fluorescence and UV–Vis), which implement a viable and simple approach towards

arsenic compounds, limit the widespread use of As2O3 against solid tumors [50].

phosphorylated ASK1 protein.

70 Arsenic - Analytical and Toxicological Studies

4.3. Therapeutic applications of arsenic binding to proteins

plausible targets for anticancer therapies [53].

5. Arsenic sensing

Optical sensors can be of different types depending upon the material used for sensing. The first one is nanomaterial-based assays for the detection of the arsenic in different mediums. Though the detection of arsenic is tough, but researchers are able to draw an outline about the ligands which can bind arsenic, and these ligands can be used as a binding unit in a sensing material which leads to either color change or change in emission spectrum. As arsenic is very much labile towards thiol group, a bunch of thiolated ligands are reported for arsenic binding. These ligands are dithiothreitol (DTT), reduced glutathione (GSH) and cysteine, and Figure 8 describes the chemical structure of these three ligands. Arsenic can bind with GSH and cysteine by forming As-O bond also, if no free –SH available. Except thiolated ligands, there are some ligands like humic acid [60] and N-(dithiocarboxy)-N-methyl-D-glucamine [61] which can also bind As(III) by forming As-O bond. Keeping this information in mind, gold nanoparticle-based sensors were reported for As(III) detection. The surface of the gold nanoparticles can be modified by the thiolated ligands, which after binding with As(III) showed a drastic color change to indicate the presence of the toxicant in the aqueous medium [62]. Aptamer-conjugated nanoparticles are also very effective composites which can detect arsenic in aqueous medium [63, 64] by changing the color. In all these types of detection assays, aggregation of the nanoparticles is the predominant factor to show the color change. Though these kinds of materials are responsive towards arsenic, but sensitivity is one of the issues which prevent these from field effectiveness.

Both selectivity and sensitivity are important for effective detection of arsenic. Small molecules are developed to detect different forms of arsenic in aqueous medium having good selectivity over other toxicants as well as good sensitivity. Baglan M et al. have reported a cysteine-fused tetraphenylethene, which can bind with As3+, and showed aggregation-induced emission as a signal [65]. Here, also the thiol group of cysteine acts as the dominating factor for As3+ binding and leading to the close proximity arrangement of the tetraphenylethene. More toxic As3+ can be distinguished over less toxic As5+ using this system, and the detection limit tends to 0.5 ppb, which is lower than the limit according to the World Health Organization (WHO) [66]. Keeping besides the thiol systems, Somentah et al. have designed a simple Schiff base system which can identify the most toxic AsO3 <sup>3</sup> fluorometrically. 'Off–on' system in fluorescence is always most exciting and effective for the detection of pollutants. In this work they have designed a molecule which is initially not showing any fluorescence emission, but after selective addition of AsO3 <sup>3</sup> fluorescence, signal is turned on due to intermolecular H-bonding leading to chelation-enhanced fluorescence (CHEF) [67]. Development of arsenic sensor is evolving year

Figure 8. Chemical structures of thiolated ligands (DTT, GSH and cysteine).

after year due to the need of arsenic detection. A modified coumarin derivative was documented as an As3+ sensor having a detection limit of 0.53 nM. Though the system has excellent sensitivity, but the main drawback is its incapability of detecting As3+ in aqueous media. So, the sensing system which can work effectively in aqueous media for the detection of arsenic having fluorescence property is in tremendous search till date. In search of a suitable aqueous medium arsenic sensor, an inorganic co-crystal has been reported having a unique luminescent response to detect As(III), having a detection limit of 49 pM. But these types of systems are not that much useful for real-life application [68]. Table 1 is prepared where available optical sensors are summarized.

A few small molecule sensors have been explored over the years, but the 'on-field' application is quite tough for small molecule sensors due to their low molecular weight and water solubility. To overcome such issues, polymeric sensing assays are developed as they have high molecular weight, tunable solubility by introducing hydrophilic functionality, high signal amplification and high sensitivity due to the number of more repeating units. In the field of materials science research, polymer-based substances have high priority. For sensing of arsenic, polymer-based sensing assay is very rare, with a few number of reports existing. A pyridylmethyl-appended 2-aminothiophenol with 2,6-diformyl-4-methylphenol was developed, which can detect arsenate (As(v)) selectively in aqueous medium. But the interesting fact

is that after attachment of the small molecule with polystyrene resin, the new material consists both sensing and removal property of As(V) which is very beneficial for the treatment of As(V) in drinking water practically [69]. All mentioned sensory assays are responding due to

Compounds or materials Mode of sensing with optical changes

Mechanisms of Arsenic-Induced Toxicity with Special Emphasis on Arsenic-Binding Proteins

http://dx.doi.org/10.5772/intechopen.74758

73

Types of sensors

2. Small molecule-based

3.Polymerbased

1.

2.

1.

2.

Table 1. Some available optical arsenic sensors and their mode of detections.

Table 1. Some available optical arsenic sensors and their mode of detections.

after year due to the need of arsenic detection. A modified coumarin derivative was documented as an As3+ sensor having a detection limit of 0.53 nM. Though the system has excellent sensitivity, but the main drawback is its incapability of detecting As3+ in aqueous media. So, the sensing system which can work effectively in aqueous media for the detection of arsenic having fluorescence property is in tremendous search till date. In search of a suitable aqueous medium arsenic sensor, an inorganic co-crystal has been reported having a unique luminescent response to detect As(III), having a detection limit of 49 pM. But these types of systems are not that much useful for real-life application [68]. Table 1 is prepared where

A few small molecule sensors have been explored over the years, but the 'on-field' application is quite tough for small molecule sensors due to their low molecular weight and water solubility. To overcome such issues, polymeric sensing assays are developed as they have high molecular weight, tunable solubility by introducing hydrophilic functionality, high signal amplification and high sensitivity due to the number of more repeating units. In the field of materials science research, polymer-based substances have high priority. For sensing of arsenic, polymer-based sensing assay is very rare, with a few number of reports existing. A pyridylmethyl-appended 2-aminothiophenol with 2,6-diformyl-4-methylphenol was developed, which can detect arsenate (As(v)) selectively in aqueous medium. But the interesting fact

1. ,

Compounds or materials Mode of sensing with optical changes

available optical sensors are summarized.

72 Arsenic - Analytical and Toxicological Studies

2.

3.

Types of sensors

1.Nanoparticlebased

> is that after attachment of the small molecule with polystyrene resin, the new material consists both sensing and removal property of As(V) which is very beneficial for the treatment of As(V) in drinking water practically [69]. All mentioned sensory assays are responding due to

mechanisms have been proposed for the toxicity of the arsenic. The mechanisms involved in the arsenic-induced carcinogenesis are also diverse and complicated. DJ-1 is a multifunctional protein that is activated upon cellular stress response. Most of the studies on DJ-1 protein are related to oxidative stress, although implication of its activity in ER stress response has been shown. The interaction of arsenic with sulfhydryl groups in proteins is considered one of the principal mechanisms which triggers the cellular responses. The binding of trivalent arsenicals to thiols in intracellular and cell surface proteins often results in aberrations of normal cellular processes including alteration of cell–cell communication. Cell–cell communication mediated by connexins, especially Cx43, the most commonly expressed connexin in different cell types, is also disrupted by arsenic binding to its highly conserved cysteine residues. In general, the effect of direct binding of arsenic species to enzyme activity cannot be ruled out in toxicity-related investigations, where other factors like the reactive oxygen species are often implicated. New methodologies are needed to analyze the health effects of arsenic and how people cope with the socioeconomic consequences of the disease. Arsenic toxicity being a global phenomenon constitutes a major public

Mechanisms of Arsenic-Induced Toxicity with Special Emphasis on Arsenic-Binding Proteins

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The study of mechanisms of arsenic-induced toxicity with special emphasis on arsenic-binding proteins is supported by the Indian Institute of Science Education and Research Kolkata (IISER-K), India. The success of this work has largely depended on the contribution and devotion of the PhD students, project students and many collaborators whose names are listed in the references.

, Soumya Kundu<sup>1</sup>

, Debnath Pal<sup>3</sup> and Jayasri Das Sarma<sup>1</sup>

,

\*

The authors declare no conflict of interest pertaining to the contents of this chapter.

1 Department of Biological Sciences, Indian Institute of Science Education and Research,

2 Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science

3 Department of Computational and Data Sciences, Indian Institute of Science, Bangalore,

, Vineeth Andisseryparambil Raveendran<sup>1</sup>

, Raja Shunmugam<sup>2</sup>

\*Address all correspondence to: dassarmaj@iiserkol.ac.in

Education and Research, Kolkata, Mohanpur, West Bengal, India

Kolkata, Mohanpur, West Bengal, India

health issue, and therefore an intense research is warranted.

Acknowledgements

Conflict of interest

Author details

Tapendu Samanta<sup>2</sup>

Karnataka, India

Afaq Hussain<sup>1</sup>

Figure 9. Cartoon representation to demonstrate change in color of PNor-Rh-coated paper strip in the absence and presence of As(III).

interaction of host and guest. But one of the best indirect As(III) sensors is reported in recent time. Sourav et al. reported one norbornene-derived rhodamine B, which is capable of detecting As(III) in aqueous medium up to 200 nM concentration [70]. Here, the main dominating factor is the oxidation of As(III) to As(V) in the presence of potassium iodate and concentrated HCl. During this oxidation procedure, iodine is liberated which coordinates with sensing molecule Nor-Rh, which leads to the colorimetric as well as fluorescence change. The effectiveness of this work is that the polymeric material of Nor-Rh can be used to make paper strip which will help to detect As(III) in real environmental samples. A cartoon representation is given in Figure 9 to demonstrate the color change of polymer-coated paper strip with and without As(III).

In summary, though few reports are available for efficient detection of arsenic in aqueous medium with high sensitivity, research community continuously tries to develop sensory assay for 'on-field' application, with a tremendous impact in detection of arsenic in environmental samples with ease and real-life application.
