**2. Detection of neurotransmitters**

Among the neurotransmitters, biogenic amines (BA) are of particular interest due to their impact in areas ranging from biomarkers of specific diseases [5–7] to quality control of foodstuffs [8, 9]. Nitric oxide (NO) is also very important neurotransmitter in the central, peripheral, and enteric nervous systems (ENS) [10, 11].

Dopamine, the simplest biogenic catecholamine (CA), is an important neurotransmitter of the central and peripheral nervous systems [12]. An approach for the colorimetric detection of dopamine has been developed using 4-amino-3-hydrazino-5-mercapto-1,2,4-triazol functionalized AuNPs (**Figure 2**).

**15**

observable by naked eye.

than dopamine.

**Figure 2.**

is achieved by modifying nanoparticle size.

*Dopamine detection using triazol functionalized AuNPs.*

*Red or Blue? Gold Nanoparticles in Colorimetric Sensing DOI: http://dx.doi.org/10.5772/intechopen.80052*

Dopamine induced the aggregation of the AuNPs through hydrogen bonding interactions [13]. Each dopamine molecule has three H-donor groups, which are able to form hydrogen bonds (the amino and both hydroxyl groups). On the other hand, the 4-amino-3-hydrazino-5-mercapto-1,2,4-triazol presents two hydrogen bond acceptors that can interact with the target molecule, inducing aggregation with the concomitant color change. Epinephrine, norepinephrine, and isoprenaline were tested as possible interferants. The three compounds showed lower responses

Following the same approach, several functionalized AuNPs have been reported [14–16] for dopamine detection in biological media. This neurotransmitter has also been detected using unmodified citrate-capped gold nanoparticles [17]. A net of hydrogen bonds among dopamine molecules and dopamine with citrate is responsible for the aggregation of the nanoparticles (**Figure 3**). Selectivity toward dopamine

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that plays a key role in the regulation of various biological functions. 5-HT has been used as a biomarker to detect the presence of carcinoid tumors. A selective and sensitive probe based on AuNPs for detecting serotonin has been reported [18]. In this case, AuNPs were bi-functionalized with dithiobis(succinimidyl propionate) (DSP) and with *N*-acetyl-L-cysteine (NALC). DSP reacts with the amino group of 5-HT, and NALC is able to interact with the hydroxyl group of serotonine through electrostatic interactions and hydrogen bonds formation, and additionally, it also acts as a stabilizer of the colloidal solutions of AuNPs due to its negative charge at neutral pH (**Figure 4**). In the presence of the analyte, aggregation takes place and the solution color changes from red to blue, being this change

Nitric oxide (NO) is one of the gaseous neurotransmitters. NO is generated in the nitric oxide synthase catalyzed oxidation of L-arginine to L-citrulline and is involved in a variety of important biological processes. For example, it stimulates *Gold Nanoparticles - Reaching New Heights*

Among the different approaches for colorimetric sensing, the use of gold nanoparticles (AuNPs) as scaffolds and signaling units for the construction of molecular sensors has attracted enormous interest for several reasons: They can be easily synthesized from Au(III) salts in various sizes and shapes. Their surface can be functionalized with a wide range of thiol- or disulfide-terminated organic ligands, by ligand exchange reactions, through the formation of strong Au–S bonds, leading to stable colloidal suspensions in water or organic solvents (depending on the ligand). Finally, gold nanoparticles have remarkable optoelectronic properties. In particular, the localized surface plasmon resonance (SPR) gives rise to a strong absorption band in the visible region. This SPR band is influenced not only by the size and shape of the nanoparticles but also by the dielectric properties of the environment and the proximity of other nanoparticles [1, 2]. This last property is the basis for colorimetric assays using AuNPs. Thus, analyte-triggered aggregation of AuNPs results in an important bathochromic shift of the SPR band (from ca. 520 to ca. 650 nm) and a change in the color of the colloidal solution from red (dispersed) to blue (aggregated) due to interparticle surface plasmon coupling (**Figure 1**). Moreover, AuNPs have very high molar extinction coefficients (ε) (ca. 108

*Analyte-induced aggregation of gold nanoparticles with concomitant changes in the color of the colloidal* 

for AuNPs with diameters between 10 and 50 nm), which confers this sens-

ing method a great sensitivity. In fact, the color change associated to the aggregation process can be observed by naked eye even at nanomolar concentration [3, 4].

the nature of the molecular interaction leading to the aggregation process.

The main challenge in the design of colorimetric sensors with AuNPs is the election of the recognition units to be attached onto the surface of the nanoparticles and

A large number of target analytes (metal ions, anions, small organic molecules, or large biomolecules) have been detected using functionalized AuNPs as colorimetric probes. However, in this chapter, the discussion has been limited to the use of functionalized spherical gold nanoparticles for the detection of small molecules with biological activity, such as neurotransmitters, nerve agents, pesticides, and

Among the neurotransmitters, biogenic amines (BA) are of particular interest due to their impact in areas ranging from biomarkers of specific diseases [5–7] to quality control of foodstuffs [8, 9]. Nitric oxide (NO) is also very important neurotransmitter in the central, peripheral, and enteric nervous systems (ENS) [10, 11]. Dopamine, the simplest biogenic catecholamine (CA), is an important neurotransmitter of the central and peripheral nervous systems [12]. An approach for the colorimetric detection of dopamine has been developed using 4-amino-3-hydrazino-5-mercapto-1,2,4-triazol functionalized AuNPs (**Figure 2**).

–109

**14**

M<sup>−</sup><sup>1</sup> cm<sup>−</sup><sup>1</sup>

**Figure 1.**

*suspensions.*

biologically relevant carboxylates.

**2. Detection of neurotransmitters**

**Figure 2.** *Dopamine detection using triazol functionalized AuNPs.*

Dopamine induced the aggregation of the AuNPs through hydrogen bonding interactions [13]. Each dopamine molecule has three H-donor groups, which are able to form hydrogen bonds (the amino and both hydroxyl groups). On the other hand, the 4-amino-3-hydrazino-5-mercapto-1,2,4-triazol presents two hydrogen bond acceptors that can interact with the target molecule, inducing aggregation with the concomitant color change. Epinephrine, norepinephrine, and isoprenaline were tested as possible interferants. The three compounds showed lower responses than dopamine.

Following the same approach, several functionalized AuNPs have been reported [14–16] for dopamine detection in biological media. This neurotransmitter has also been detected using unmodified citrate-capped gold nanoparticles [17]. A net of hydrogen bonds among dopamine molecules and dopamine with citrate is responsible for the aggregation of the nanoparticles (**Figure 3**). Selectivity toward dopamine is achieved by modifying nanoparticle size.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that plays a key role in the regulation of various biological functions. 5-HT has been used as a biomarker to detect the presence of carcinoid tumors. A selective and sensitive probe based on AuNPs for detecting serotonin has been reported [18]. In this case, AuNPs were bi-functionalized with dithiobis(succinimidyl propionate) (DSP) and with *N*-acetyl-L-cysteine (NALC). DSP reacts with the amino group of 5-HT, and NALC is able to interact with the hydroxyl group of serotonine through electrostatic interactions and hydrogen bonds formation, and additionally, it also acts as a stabilizer of the colloidal solutions of AuNPs due to its negative charge at neutral pH (**Figure 4**). In the presence of the analyte, aggregation takes place and the solution color changes from red to blue, being this change observable by naked eye.

Nitric oxide (NO) is one of the gaseous neurotransmitters. NO is generated in the nitric oxide synthase catalyzed oxidation of L-arginine to L-citrulline and is involved in a variety of important biological processes. For example, it stimulates

#### **Figure 3.**

*Mode of interaction and colorimetric response of AuNPs with four different particle sizes against catecholamines (CAs). Experimental conditions: CCAs = 4 μM, CNaCl = 14 mM, pH = 7.0, and incubation time: 10 min. NP1: 13 nm AuNPs; NP2: 23 nm AuNPs; NP3: 32 nm AuNPs; and NP4: 43 nm AuNPs.*

#### **Figure 4.** *Detection of serotonin with DSP and NALC functionalized AuNPs.*

the production of cyclic guanosine monophosphate (cGMP) which acts as a second messenger. In addition, nitric oxide is released by some neurons that innervate the gastrointestinal tract, penis, respiratory passages, and cerebral blood vessels. Nitric oxide is also released as a neurotransmitter in the brain and has been implicated in the processes of learning and memory. Detection of this gas has been carried out using functionalized AuNPs that aggregates through NO-induced "click" reaction [19]. To detect the analyte, both azide- and terminal alkyne-functionalized gold nanoparticles were synthesized.

**17**

was 81 ppm.

**Figure 5.**

*Red or Blue? Gold Nanoparticles in Colorimetric Sensing DOI: http://dx.doi.org/10.5772/intechopen.80052*

**3. Detection of nerve agents and pesticides**

The prepared sensor showed high sensitivity [23].

ing aggregation (**Figure 6**).

The sensing mechanism is shown in **Figure 5**. The initial aqueous solution containing a mixture of azide- and terminal-alkyne functionalized AuNPs remains dispersed in the presence of Cu(II), with its characteristic red-wine color. When NO is added to the solution, Cu(II) is reduced to Cu(I), and then, the "click" reaction between azide and alkyne-terminated nanoparticles takes place, giving rise to the nanoparticles aggregation with the subsequent change in the color of the solution.

*Mechanism for detecting NO with a mixture of azide and alkyne functionalized AuNPs.*

The current rise in international concern over the use of chemical warfare (CW) agents in different conflictive sceneries has resulted in an increasing interest in the detection of these lethal chemicals. Among CW species, nerve agents are greatly dangerous and their high toxicity and easy production underscore the need to detect these deadly chemicals via quick and reliable procedures. AuNPs have been used as sensors for some nerve agent simulants with good results. Different sensing mechanisms have been used for detecting these compounds, for example, compensation of charges has been applied for this process [20]. The designed sensing protocol takes advantage of the nucleophilic reactivity of pyridine moieties toward nerve gases [21]. This reactivity generates positive charges on the surface of the gold nanoparticles, diminishing their colloidal stability and induc-

Several pyridine derivatives were studied, and their ability to act as probes for DCNP detection was evaluated by UV-vis spectroscopy. After addition of increasing amounts of DCNP, the intensity of the surface plasmon peak of the monodispersed AuNPs at 526 nm decreased and a new peak at c.a. 660 nm appeared as the AuNP clusters were formed. The best results were obtained with compound **1** (**Figure 6c**) that showed a limit of detection of 76 ppm under the experimental conditions used. Following the same approach, compound **2** (**Figure 7**) was bound to gold nanoparticles. In this case, the positive charge appears as a consequence of the reaction described in **Figure 7**. The limit of detection determined in this case

Also, triarylcarbinols have been used as recognition motifs. These compounds can be converted into their corresponding carbocations in the presence of nerve agent simulants through phosphorylation of the OH group followed by SN1 elimination. Consequently, AuNPs functionalized with this type of compounds have been used in detecting simulants of these dangerous compounds (**Figure 8**, X = F, CN) [22].

An approach based on enzymatic reactions has also been described for detecting nerve agents GB, GD, and VX and the highly toxic pesticide paraoxon (**Figure 9**).

*Red or Blue? Gold Nanoparticles in Colorimetric Sensing DOI: http://dx.doi.org/10.5772/intechopen.80052*

*Gold Nanoparticles - Reaching New Heights*

**Figure 3.**

**16**

**Figure 4.**

nanoparticles were synthesized.

*Detection of serotonin with DSP and NALC functionalized AuNPs.*

the production of cyclic guanosine monophosphate (cGMP) which acts as a second messenger. In addition, nitric oxide is released by some neurons that innervate the gastrointestinal tract, penis, respiratory passages, and cerebral blood vessels. Nitric oxide is also released as a neurotransmitter in the brain and has been implicated in the processes of learning and memory. Detection of this gas has been carried out using functionalized AuNPs that aggregates through NO-induced "click" reaction [19]. To detect the analyte, both azide- and terminal alkyne-functionalized gold

*Mode of interaction and colorimetric response of AuNPs with four different particle sizes against* 

*catecholamines (CAs). Experimental conditions: CCAs = 4 μM, CNaCl = 14 mM, pH = 7.0, and incubation time: 10 min. NP1: 13 nm AuNPs; NP2: 23 nm AuNPs; NP3: 32 nm AuNPs; and NP4: 43 nm AuNPs.*

**Figure 5.** *Mechanism for detecting NO with a mixture of azide and alkyne functionalized AuNPs.*

The sensing mechanism is shown in **Figure 5**. The initial aqueous solution containing a mixture of azide- and terminal-alkyne functionalized AuNPs remains dispersed in the presence of Cu(II), with its characteristic red-wine color. When NO is added to the solution, Cu(II) is reduced to Cu(I), and then, the "click" reaction between azide and alkyne-terminated nanoparticles takes place, giving rise to the nanoparticles aggregation with the subsequent change in the color of the solution.
