Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters

*Ali Shee and Katrin Mackenzie*

### **Abstract**

Most halogenated organic compounds (HOCs) are toxic and carcinogenic, hence unwanted in the environment. Several technologies exist for the treatment of both legacy and newly contaminated zones. In many contaminated subsurface environments, nano zero-valent iron (nZVI) as a reagent is the tool of choice, while palladium (Pd) as a catalyst faces technical challenges. A system comprising metallic copper and borohydride as a reducing agent (referred herein as copper-borohydride system, CBHS) provides an alternative to nZVI and Pd. This chapter presents a deeper understanding of the CBHS for the treatment of HOCs by highlighting the state of knowledge related to the i) type and classes of compounds that are treatable, ii) possible reaction pathways for their transformation, iii) specific metal activities for transformation of selected classes of HOCs, iv) influence of common water constituents on catalyst stability, and v) future perspectives regarding its application in water treatment applications. Furthermore, an up-to-date discussion is presented regarding the available techniques for the synthesis of copper nanoparticles. Based on the evaluation criteria including product selectivity patterns, amount and the fate of intermediates, and metal cost and stabilities in water, the most suitable application areas for Cu, Pd, and nZVI are presented as recommendations.

**Keywords:** halogenated organic compounds (HOCs), metallic copper catalysts, palladium catalysts, reduction technologies, nano zero-valent iron, water treatment

### **1. Introduction**

Environmental contamination of soil, surface water, and groundwater with halogenated organic compounds (HOCs) continues to pose a serious threat to both human and ecological health. HOCs are indispensable in many consumer products and industrial processes, e.g. as solvents, refrigerants, and feedstocks in the manufacture of pharmaceuticals, veterinary drugs, paints, adhesives, and lacquers [1]. HOCs commonly enter the environment by improper use. That includes accidental discharge from the chemical industries, surface runoff, and improper disposal and usage. The low-molecular-weight HOCs including haloacetic acids and halomethanes are also prominent members of disinfection byproducts which are produced when natural

waters containing organic matter are treated with chlorine and chlorine-based disinfectants [2]. Chlorinated compounds become more and more insoluble in water with growing carbon chain length of 10–13 and higher chlorine content which also makes them susceptible to long-range atmospheric transport [3]. In aquatic environments, such substances undergo bioaccumulation and biomagnification in aquatic organisms, e.g. fish, crabs, oysters, etc.; thus, they enter the food chain [3–5]. In addition, human exposure to HOCs occurs via dermal absorption, inhalation, and drinking contaminated water and consumption of contaminated food [1]. Most HOCs are also toxic and possible carcinogens even at very low concentrations [6–8]. Due to their associated public health risks, the production and use of HOCs is under strict control. Many of them are placed under the Stockholm Convention on Persistent Organic Pollutants and are also placed on toxic release inventory in the European Union, Japan, Canada, and the United States [1, 3–5]. When released into the environment, most HOCs are resistant to biodegradation; hence, they are persistent. The removal of HOCs from contaminated environments is therefore of utmost importance. Several technological processes based on biological, physical, and chemical methods have been evaluated for various contaminant types. So far, there is no single technology that can be applied for the detoxification of all contamination problems. Important factors which need to be considered before selecting a treatment technology include the chemical nature of the HOCs, the nature of contaminated media, the extent of contamination, overall treatment time, cost of the treatment system, degree of detoxification, and fate of the treated media.

Biological processes in most cases are characterized by low conversion degrees of the contaminant and slow reaction rates but low maintenance. Hence, long treatment times are necessary for bringing the contaminants concentrations to levels of low toxicity. Also, microbial processes such as methanogenesis are sometimes inhibited by the presence of high concentrations of some target contaminants, e.g. chloroform (CF) [9, 10]. Air-stripping and adsorption processes for removal of HOCs from water only transfer the contaminants from one phase into another, where further treatment of the resultant effluents is necessary [11]. For adsorption processes, regeneration of the adsorber (e.g. activated carbon) or its frequent replacement is not only expensive but also timeconsuming. Incineration which is sometimes applied to more complex and toxic industrial effluents is energy-intensive and costly. The major environmental problem associated with incineration of HOCs include the release of incomplete combustion products, fly ash generation, and particularly the generation of toxic byproducts, especially polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes (PCNs) [12, 13].

Chemical destruction techniques based on photooxidation, Fenton's reagent, and advanced oxidation processes (AOPs) when applied to HOCs are characterized by low reaction selectivity and a higher probability of generating toxic and recalcitrant byproducts. Hence, the provision of excess redox equivalents is necessary when full mineralization is desired [14, 15]. Reduction processes are more suited for the treatment of HOCs than oxidation processes. Reduction involves the selective removal of the halogen (X) atoms by H-atoms (R–X + reducing agent ! R–H+H–X). Generally, the replacement of X atoms from higher halogenated contaminants results in significant detoxifications. However, there are exceptions. A prominent example is vinyl chloride (VC), which is more toxic than the higher chlorinated chloroethene homologs, e.g. perchloroethylene (PCE) [16]. The coupling of reduction processes with biological processes can sometimes be used to achieve significant detoxification [17, 18].

For about three decades (since 1994) [19], technologies employing microscale zerovalent iron (mZVI) or nano zero-valent iron (nZVI) as reagents to reduce HOCs were

### *Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters DOI: http://dx.doi.org/10.5772/intechopen.108147*

the methods of choice for *in situ* groundwater treatment of HOCs [20, 21]. Due to the higher HOCs reaction rates and better particle mobility, nZVI is widely used for direct injection into the aquifer. In the presence of water, nZVI as a reagent is consumed, thereby releasing electrons (and consecutively also hydrogen) that are essential for the cleavage of the R–X bond (R–X + Fe0 + H2O ! <sup>R</sup>–H + Fe2+ + X� + OH�). Reducing agents based on metallic iron are comparably cheap, environmentally compatible, and offers long-term treatment solutions for contaminated aquifers under anaerobic conditions. nZVI can be applied to treat mainly the halogenated alkanes and alkenes. It shows very low activity for the reduction of saturated aliphatic compounds with lower chlorination degrees such as dichloromethane (DCM) and 1,2-dichloroethane (1,2-DCA) [22, 23]. Also, iron's limitations are its inability to reduce C–Cl bonds attached to aromatic structures, especially those with lower chlorination degrees [24, 25], its tendency to deactivate under aerobic conditions, its loss of activity at pH > 10, and its consumption with time by anaerobic corrosion in water (Fe0 + 2H2O ! Fe2+ <sup>+</sup> H2 + 2OH�). The consumption of nZVI in water due to corrosion is pH-sensitive. When pH < 7 is applied, nZVI is consumed quickly producing hydrogen as the major product. At pH > 10, the coating of nZVI core with iron oxides/hydroxides occurs inhibiting further reaction. Hence for the reduction of HOCs in water by nZVI, the pH need to be maintained in the range 7–10 using suitable buffers [26].

Reduction processes catalyzed by H-activating metals, especially rhodium (Rh), platinum (Pt), and Pd, are applicable to treat a broader spectrum of compounds which include the reduction of C–X bonds attached to aromatic structures. Among the noble metals, Pd is the most potent hydrodehalogenation (HDH) catalyst. However, Pd is sensitive to deactivation due to poisoning and even self-poisoning by released hydrogen halide (HX). Nevertheless, the effect of HX can be prevented by its withdrawal from the surface through uptake by the water bulk phase or by the addition of a base, e.g. NaOH [27–30]. Whereas nZVI does not require the addition of an additional reductant, Pd must be used together with H-donors (reducing agents) such as H2, borohydride (BH4 �), Fe<sup>0</sup> as H2 producer, formic acid, hydrazine, or alike [31, 32]. The HDH reaction occurs at Pd surfaces and is mediated by activated H-species (H\*) or adsorbed surface hydrogen (Pd–Hads) [33–35]. The cleavage of R–X bonds by Pd catalyst and in the presence of hydrogen as the reductant can be described as (R– X+H2 + Pd0 ! <sup>R</sup>–H + HX + Pd<sup>0</sup> ). The specific metal activity (*A*m), which will be discussed later in this chapter, can be used to formally compare the treatment efficiencies of reagents and catalysts. *A*<sup>m</sup> is a second-order parameter that tells us the amount of metal required to treat a given amount of contaminated water per time (required number of half-lives until desired treatment goal is reached). For similar compounds and under comparable reaction conditions, the specific Pd activity (*A*Pd) seems to depend on the nature of H-donors [32]. Nevertheless, for all HOCs classes, *A*Pd is found to be between two and five orders of magnitude higher than the specific nZVI activity (*A*nZVI) [36, 37]. Pd as a catalyst is reusable several times and is required only in very small amounts. Therefore, in comparison with nZVI, only a small amount of Pd metal is necessary to treat large volumes of contaminated water in very short times. Another advantage of Pd compared to nZVI is that it can be applied over a broad range of pH (2–9) and to nearly all HOCs classes including the reduction of chlorinated aromatics [38, 39]. In comparison with nZVI, the application of Pd for the reduction of HOCs in water is not limited by pH. Nevertheless, dissolution of Pd metal under highly acidic conditions can occur [40].

Despite the huge potential of Pd in HDH reactions, its use in water treatment applications under field conditions is limited due to major drawbacks. Pd is more expensive and rarer than nZVI and is readily deactivated by manifold processes which inhibit or even destroy the catalyst function. The Pd catalyst loses its activity in the presence of macromolecular and ionic poisons such as heavy metals, organic matter (e.g. natural organic matter (NOM), humic acids (HA), and fulvic acids) [40–44]. The most significant substances with a detrimental effect on Pd are reduced sulfur compounds (RSCs), e.g. SO3 <sup>2</sup> and S2 [45]. Under anaerobic conditions, S2 can also be produced in aqueous environments by sulfate-reducing bacteria, especially in the presence of hydrogen. Regeneration of deactivated Pd catalysts using oxidants, e.g. hypochlorite is tedious, expensive, and time-consuming, results in loss of metal due to leaching and may not restore original (baseline) catalyst activity [40, 41, 44]. Also, *A*Pd values are extremely low for saturated aliphatic compounds with lower chlorination degrees such as dichloromethane (DCM) and 1,2-dichloroethane (1,2-DCA) [22, 23, 38, 39]. DCM, 1,2-DCA, and similar compounds are contaminants of interest to water treatment professionals, since they are toxic and possible carcinogens. Saturated aliphatic compounds with lower chlorination degrees such as chloromethane (CM), DCM, and chloroethane (CA) are also produced as stable byproducts during the dechlorination of the corresponding higher chlorinated homologs. For example, the dechlorination of CF and carbon tetrachloride (CTC) by nZVI and Pd produces CM and DCM as recalcitrant byproducts [22, 38, 46, 47]. Similarly, CA is usually a dead-end byproduct during the dechlorination of 1,1,1-trichloroethane (1,1,1-TCA) by nZVI and Pd [23, 38].

Cu is the eighth most abundant element of the earth's crust, and its unique properties such as good ductility, malleability, high thermal and electrical conductivity, and high corrosion resistance make it suitable for a broad range of applications. Common applications for metallic Cu catalysts include oxidative degradation of HOCs [48], NOx reduction [49], CO2 reduction [50], electrocatalytic reduction of chlorinated alkanes [51–53], and aryl coupling reactions [54, 55]. Despite this widespread application, the utilization of metallic Cu as reduction catalysts for the treatment of HOCs in water is limited. Under ambient conditions (1 atm and 25°C) and in water, metallic Cu is less reactive toward the activation of H2 into H\*. Hence, it must be used together with a more reactive reductant such as BH4 (*E*° = 1.24 V vs. standard hydrogen electrode (SHE)) [56]. In this chapter, CHBS represents Cu + BH4 . The HDH reaction by the copper-borohydride system (CBHS) may be mediated by several reactive species. The cleavage of R–X bonds could be mediated by surface adsorbed Hspecies or hydrides [57–59]. Like in hydrosilylation reactions, the insertion of Cu species may as well be implicated [60, 61]. In this chapter, we review important literature to provide a deeper understanding of the CBHS for the reductive treatment of HOCs in water. Consideration will focus on product selectivity patterns, specific Cu activities (*A*Cu), and catalyst stability in water. For a broad spectrum of HOCs, the HDH ability of the CBHS is compared with the common reduction tools based on nZVI and Pd. The comparison is intended to provide a guide to water treatment professionals during the decision-making process in selecting an appropriate tool that is best suited to a particular class of HOCs under certain reaction conditions. In order to do the comparison, several essential criteria are defined in this chapter.

### **2. Evaluation criteria for reagents and catalysts**

The evaluation of the efficiency of a treatment system involves several parameters which are discussed in this section. Conversion (*X*HOC) which shows the fraction of a given contaminant transformed at any given time can be calculated using Eq. (1):

*Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters DOI: http://dx.doi.org/10.5772/intechopen.108147*

$$X\_{\text{HOC}} = \left(\mathbf{1} - \frac{n\_{\text{HOC},t}}{n\_{\text{HOC},0}}\right) \times \mathbf{100}\mathbf{9\%}\tag{1}$$

where *n*HOC,t represents the moles of educt at any given time (mol) and *n*HOC,0 refers to the initial moles of educt fed into the batch reactor at *t* = 0 (mol). The product yield (*Y*i,product) which shows the amount of product formed with respect to the initial moles of educt fed into the reactor is calculated based on Eq. (2):

$$Y\_{i, \text{product}} = \frac{n\_{i, \text{product}}}{n\_{\text{HOC,0}}} \times \mathbf{100\%} \tag{2}$$

where *n*i,product represents the moles of product i obtained at a given time (mol). In order to determine the actual amount of product formed with respect to the actual amount of educt transformed at any given time, product selectivity (*S*i,product) can be calculated based on Eq. (3):

$$\text{S}\_{\text{i,product}} = \frac{n\_{\text{i,product}}}{n\_{\text{convected HOC}}} \times 100\text{\%} \tag{3}$$

where *n*converted,HOC represents the moles of educt converted at the given time (mol). In order to determine the reaction rates for the transformation of HOCs using nZVI, Pd, and Cu, the pseudo-first-order kinetics as shown in Eq. (4) can be applied:

$$\frac{dc\_\mathrm{i}}{dt} = -k\_{\mathrm{obs}} \cdot c\_\mathrm{i} \tag{4}$$

where *c*<sup>i</sup> represents the concentration of HOCs (mg/L), while *k*obs is the pseudofirst-order rate constant (1/min). For slow-reacting compounds, such as CA, that are characterized by lower conversion degrees, *k*obs can conveniently be calculated from products formation as shown in Eq. (5):

$$\operatorname{Im}\left(\mathbf{1} - \frac{c\_{\text{i,product}}}{c\_{\text{product, max}}}\right) = -k\_{\text{obs}} \cdot t \tag{5}$$

where *c*i,product and *c*product,max represent the concentration of product at the given time (mg/L) and the maximum concentration of product (mg/L), respectively, while *t* refers to the reaction time (min). The value of *k*obs calculated based on Eq. (4) and Eq. (5) and for metal particles with similar particle sizes can be used to compare the HDH ability of a remediation tool only for HOCs transformation reactions carried out under similar reaction conditions (same metal concentrations and reaction pH). Since in most cases reaction conditions are hardly the same, the surface area-normalized rate constant (*k*SA in [L/(m<sup>2</sup> �min)]) that is calculated based on Eq. (6) can be used:

$$k\_{\rm SA} = \frac{k\_{\rm obs}}{c\_{\rm m} \cdot a\_{\rm s}} \tag{6}$$

where *c*<sup>m</sup> is the concentration of the metal (g/L) and *ɑ*<sup>s</sup> is the metal-specific surface area (m<sup>2</sup> /g). The value of *ɑ*<sup>s</sup> is commonly obtained from N2 adsorption/desorption (Brunauer–Emmett–Teller (BET)) measurements. The use of *k*SA assumes that the entire exposed surface area of the metal participates in the reaction. Based on this understanding, nanosized particles which have larger available surface areas are

preferred for HDH reactions compared to their micro-sized particles. However, it is noteworthy to point out that for heterogeneous systems, only a fraction of the available surface area takes part in the HDH reaction. Specifically, only the available surface atoms as determined by dispersion data (from CO chemisorption measurements) are involved. In the absence of metal dispersion data, the specific metal activity (*A*m) which is calculated as shown in Eq. (7) can be used:

$$A\_{\rm m} = \frac{V\_{\rm w}}{m \cdot \tau\_{\rm t\natural}} = \frac{1}{c\_{\rm m} \cdot \tau\_{\rm t\natural}} = \frac{\text{In } (c\_{t1}/c\_{t2})}{\ln 2 \cdot c\_{\rm m} \left(t\_2 - t\_1\right)} = \frac{k\_{\rm obs}}{\ln 2 \cdot c\_{\rm m}} \left[\text{L}/(\text{g} \cdot \text{min})\right] \tag{7}$$

where *V*<sup>w</sup> is the volume of the water contaminated with HOCs (L), *m* refers to the metal mass (g), and *τ*<sup>½</sup> refers to the HOCs half-life (min) obtained from the pseudofirst-order kinetics profile. The variables *c*t1 and *c*t2 refer to the concentrations of contaminants at any two sampling times *t*<sup>1</sup> and *t*2, respectively. *A*<sup>m</sup> can be used for different metals which have nearly the same particle sizes to provide a solid comparison where dispersion data is not available. In terms of technical and economical points of view, *A*<sup>m</sup> shows the amount of metal required to treat a given volume of contaminated water in several half-lives. By using *A*<sup>m</sup> as a basis for comparing the dehalogenation abilities of nZVI, Pd, and Cu, it is important to point out that we are comparing three "reduction systems" and not the metals, because different reductants are applied (BH4 �, H2, and Fe<sup>0</sup> ).

### **3. Synthesis strategies for copper nanoparticles (Cu NPs)**

The synthesis of Cu nanoparticles (Cu NPs) can be done by using physical, biobased, and chemical methods. Top-down or physical methods are used to reduce bulk material into nanosized dimensions by mechanical milling, grinding, cutting, etching, laser ablation, vacuum vapor deposition, and pulsed wire discharge [62, 63]. Topdown methods are less preferred; since it is difficult to obtain Cu NPs with uniform sizes, they are energy-intensive and require specialized equipment and technical knowledge.

Bio-based methods for the synthesis of Cu NPs employ the use of plant extracts and microorganisms. Cu NPs can be produced by heating a mixture of plant extracts and copper salts. The reducing and stabilizing agents present in plant extracts include phenols, flavonoids, proteins, tannins, and terpenoids. Common microorganisms used include bacteria, fungi, and green algae [64, 65]. Bio-based methods are preferred because they are considered cost-effective and environmentally friendly. For the rapid and large-scale synthesis of Cu NPs, chemical reduction techniques are preferred over biological methods.

Bottom-up approaches involve the synthesis of Cu NPs from a copper salt or copper oxide. Common bottom-up methods applied include chemical reduction, sonochemical reduction, micro-emulsion techniques, electrochemical reduction, hydrothermal or sol–gel synthesis, polyol, and microwave irradiation [62, 63]. Chemical reduction techniques for the synthesis of Cu NPs are the most common, since they are simple and usually have the tendency to produce smaller and uniform nanoparticles. Furthermore, in chemical reduction methods, nanoparticles of desired sizes and morphology can be obtained by manipulation of reaction conditions, e.g. time, pH, solvent, and suspension stabilizer. The reduction of a copper salt can be done using reductants such as BH4 � and hydrazine combined with stabilizers

*Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters DOI: http://dx.doi.org/10.5772/intechopen.108147*

including ascorbic acid, starch, poly(ethylene glycol), poly(vinylpyrrolidone) (PVP), cetyltrimethylammonium bromide, poly(acrylic acid) (PAA), and carboxymethyl cellulose (CMC). When stabilizers are used, the reaction mixture needs to be refluxed at 60–100°C for about 30–120 min.

The most widely used method for the synthesis of Cu NPs in water and under ambient conditions involves the reduction of a copper precursor with sodium borohydride (NaBH4). This method is preferred, since it is simple to implement and produces nanoparticles with uniform sizes, narrow size distribution range, and uniform surface morphology [66, 67]. Under ambient conditions and in water, BH4 is unstable and the decomposition rate is pH-sensitive [58, 68, 69]. Therefore, to control BH4 decomposition, reaction pH ≥ 10 is ideal for the growth and development of Cu NPs. The recommended molar ratio for Cu2+ : NaBH4 is 1 : 8. A lower molar ratio between Cu2+ and NaBH4 is characterized by a slower reaction and nonuniform particle sizes. To prevent agglomeration of the freshly prepared nanoparticles, the stabilizers (PVP, PAA, CMC, etc.) are usually introduced already during the synthesis process.

### **4. Reduction of HOCs in water: Comparison of Cu, Pd, and nZVI**

The CBHS for reduction of HOCs in water has received less attention than with Pd + H2 and nZVI. Previous work applied the CBHS for dechlorination of DCM [66], 1,2-DCA [67], and selected monochloroaromatics [70]. Recently, a deeper understanding of the system was applied to a broad spectrum of HOCs, highlighting product selectivity patterns, reaction rates of the individual compounds, and the efficiency of the system in comparison with Pd and nZVI [36, 37]. The HDH ability of the CBHS for the treatment of saturated aliphatic HOCs is markedly superior to nZVI and Pd. This section provides an extensive overview of the HDH abilities of the three systems. Evaluation criteria include reduction (dehalogenation) rates of individual HOCs, product selectivity patterns, amount and fate of chlorinated intermediates, metal cost, and metal stability in water. It is noteworthy to point out this is not a comparison of the individual metals but rather a comparison of their reduction abilities (Cu + BH4 , Pd + H2, and nZVI). Using both experimental and literature data, Shee (2021) calculated the specific metal activities for the reduction of individual HOCs in water using Cu, Pd, and nZVI as shown in **Table 1**. The data in **Table 1** were calculated using nanoparticles of comparable dimensions (*d*50,Cu = 50 nm, *d*50,Pd = 60 nm, and *d*50,nZVI = 75 nm) [36].

From the data in **Table 1**, for most compounds, the ease of dehalogenation is based on the weakest C–X bond strengths.

Since C–Br (285 kJ/mol) are weaker than C–Cl bonds (337 kJ/mol), brominated compounds show higher *A*<sup>m</sup> values than their chlorinated counterparts. As can be seen in **Table 1**, for Cu, the dehalogenation rates (presented as *A*Cu) for halogenated methanes and ethanes depend on i) the strength of the weakest C–X bond and ii) the number of geminal X atoms. The *A*Cu values are generally inversely proportional to the strength of the calculated C–X bonds. For example, *A*Cu,CTC is five orders of magnitude higher than *A*Cu,DCM. For the chlorinated ethanes, their reactivity depends not only on the number of Cl atoms but also on the number of geminal Cl atoms. An increase in the number of geminal Cl atoms leads to i) a decrease in C–Cl bond strengths and ii) an increase in the initial attachment of Cl atoms to the catalyst surface. This trend in reactivity for chlorinated methanes and ethanes was also observed for reactions carried out in the gas phase using solid metallic Cu [71] and Pd



### *Calculated specific metal activities for the dehalogenation of single HOCs in water using Cu-, Pd-, and nZVI-based systems and the corresponding weakest C–X bond dissociationenergies.*

**Table**

**1.**

### *Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters DOI: http://dx.doi.org/10.5772/intechopen.108147*

[72, 73]. The correlation between reactivity and the weakest C–X bond strength shows that the HDH reactions at Cu and Pd surfaces for saturated aliphatic HOCs follow similar reaction mechanisms. Hence, the cleavage of the C–X bond is rate-determining and involves homolytic cleavage of the weakest C–X bond (R–X ! R� + X�). It is also important to point out that the adsorption strengths of X atoms at the catalyst surface are essential for bond cleavage. During aqueous phase hydrodechlorination (HDC) of CTC and CF by Cu and Pd, radical coupling byproducts such as ethane and ethene [37, 46] were detected in trace amounts. Homolytic cleavage of CF and CTC to form dichloromethyl and trichloromethyl radicals, respectively, is therefore ratedetermining. Radical coupling reactions are only minor. The radical intermediates undergo further reactions to form various products, e.g. methane (CH4), CM, and DCM [22, 37].

In environmental catalysis, the proportion of the fully dechlorinated product with respect to the chlorinated intermediates, i.e. selectivity, is essential in evaluating the efficiency of a treatment system. By using compounds with the general formula CCl3– R where R = H, F, Cl, Br, and CH3, the CBHS was applied to evaluate product selectivity patterns [37]. By using CF (where R = H) as a model compound, it was found that for both Cu and Pd, the selectivity to DCM was 10–15 mol-%. Further assessment of the ratio of specific metal activities for dechlorination of CF and DCM using Cu and Pd, *A*Cu,CF/*A*Cu,DCM = 591 and *A*Pd,CF/*A*Pd,DCM = 531, respectively, show that both systems have a problem with DCM formation. In the same study, it was reported that for nZVI, CM and DCM selectivities were 30–40 mol-% and 35–45 mol- %, respectively, and *A*nZVI = 0.003 � 0.001 L/(g�min). Further assessment of the CBHS showed that variation in reaction conditions, e.g. catalyst amount, type, and concentration of reductants and catalysts support, had no significant effect on DCM selectivity. A multi-catalytic approach was essential in changing DCM selectivity. DCM selectivity was decreased by more than 80% by combining the CBHS with either silver (Ag) or vitamin B12. Whereas CM and DCM remain more-or-less as dead-end byproducts when Pd and nZVI are used for the dechlorination of CF and CTC, the CBHS readily dechlorinates these compounds in subsequent steps [37]. This ability of CBHS to dechlorinate DCM and similar compounds (see **Table 1**) makes it more appropriate for the treatment of saturated aliphatic HOCs. Therefore, metallic Cu can be considered the "agent of choice" for the treatment of these classes of compounds in highly contaminated wastewaters.

Similar to the halogenated methanes and ethanes, brominated ethenes are more easily transformed than their chlorinated counterparts (see **Table 1**). This could be attributed at least to the strength of the C–Br and C–Cl bonds. However, the HDC mechanism for chlorinated ethenes is not as straightforward as that of the chlorinated methanes and ethanes. Both Mackenzie et al. (2006) and Shee (2021) have demonstrated that the HDC rates for chlorinated ethenes are independent of the C–Cl bond strengths. For chlorinated ethenes, two reaction steps are involved: i) cleavage of the C–Cl bond and ii) hydrogenation of the double bond. Mackenzie et al. (2006) have shown that the rate-determining step for HDC of chlorinated ethenes by Pd is a concerted step involving the addition of H\* to the double bond and simultaneous cleavage of the C–X bond. The hydrogenation of the double bond occurs later after the cleavage of the C–X bond. For compounds containing pi-systems, the essential step is C=C di-δ bond formation at the catalyst surface (active centers) [39, 74, 75]. However, it is important to point out that in addition to C=C di-δ bonding, the Cl atoms also interact with the catalyst surface. Hence, dissociative adsorption of the C–Cl bonds followed by hydrogenation of C=C bonds are characteristic reaction steps for

### *Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters DOI: http://dx.doi.org/10.5772/intechopen.108147*

chlorinated ethenes. Based on this description, Pd as a potent hydrogenation catalyst smoothly dechlorinates chlorinated ethenes. For all halogenated ethenes (see **Table 1**), *A*Pd increases with increasing C–Cl bond strengths. Hence, the order of reactivity for Pd is VC > DCE isomers > TCE > PCE. In general, *A*Pd values for all compounds (see **Table 1**) are two to three orders of magnitude than *A*Cu values. For the CBHS, there is no clear distinction in the reactivity of the chlorinated ethenes. The *A*Cu values differ only by one order of magnitude which is less significant. Therefore, in the HDC of chlorinated ethenes by the CBHS, we suggest that the lower *A*Cu values could be due to i) minimal interaction of the C=C bond with the metallic Cu surface for di-δ bonding, and ii) the actual reductants could be adsorbed hydride species (Cu–H) instead of H\* that are predominant in Pd. Although the *A*nZVI values for reduction of halogenated ethenes are five to eight orders of magnitude lower than *A*Cu and *A*Pd, it can be considered the "agent of choice" for *in situ* treatment of the highly chlorinated homologs, PCE and TCE. Fe is abundant in nature; it is cheaper than both Pd and Cu; it is environmentally compatible and does not require the addition of a reductant. Furthermore, the formation of an oxidic layer that protects the metallic nZVI core offers a long-term treatment solution for contaminated plumes and groundwater. Since the transformation of TCE and PCE results to accumulation of VC and the DCE isomers with time, coupling nZVI with microbial processes can achieve significant detoxification. However, for the treatment of chlorinated ethenes derived from industrial processes where rapid detoxification is desired, Cu catalysts are in such cases more appropriate than nZVI.

Other than halogenated alkanes and alkenes, halogenated aromatic compounds (HACs) are also a significant class of environmental contaminants. These compounds are more hydrophobic than the corresponding aliphatic HOCs. In the presence of organic matter, HACs are strongly immobilized in soil compartments and sediments [76, 77]. Hence before treatment, the HACs need to be desorbed using solvents and surfactants. *Ex situ* treatment technologies such as soil washing and pump and treat need to consider that the extraction solvent constitutes a cocktail of HACs, solutes, heavy metals, and organic matter. Most of the matrix components are catalysts inhibitors, and therefore pretreatment steps such as coagulation, flocculation, and filtration need to be considered. For the CBHS, Shee (2021) has demonstrated that Cu is rather resistant to deactivation by most water matrix constituents including S<sup>2</sup> and SO3 2. In contrast, Pd is known to undergo either partial or permanent deactivation in the presence of several solutes from soil washing processes. RSCs are the most dangerous poisons whose presence even in trace levels leads to permanent catalyst deactivation [40, 42, 44, 45, 78]. In order to prolong Pd activity, several protection steps have been investigated with little success. These include i) pretreatment steps such as coagulation, flocculation, sedimentation, and filtration steps to precipitate heavy metals and organic macromolecules, ii) addition of oxidants to convert RSCs into nondeactivating substances, e.g. SO4 <sup>2</sup> [78], iii) regeneration of the fouled catalysts by the addition of oxidants such as KMNO4, H2O2, and hypochlorite, and iv) minimizing contact between the poisons and catalysts by introducing a protective layer of adsorbent, e.g. zeolites, silica material, and poly(dimethylsiloxane) (PDMS) [40, 79–81].

In addition to water matrix composition, the reaction rates of the individual HACs are important in selecting the appropriate reduction system. Numerous literature studies show that unmodified nZVI is able to dechlorinate chlorobenzene (CB) and dichlorodiphenyltrichloroethane (DDT) [82–84]. However, these studies are subject to debate. nZVI is an electron-transmitting reagent, and the transfer of an electron leading to cleavage of the weakest C–X bond is rate-controlling. For HACs, the

cleavage of the C–X bond involves at least two important steps [85] which are described in Eq. (8) and Eq. (9).

i. Formation of a radical anion as a true intermediate after the first electron transfer step:

$$(\mathbf{ArX} + \mathbf{e} \to [\mathbf{ArX}]) \tag{8}$$

ii. Formation of an aryl radical and halide anion:

$$([\mathbf{ArX}]^{-} \cdot \to \mathbf{Ar} \cdot + \mathbf{X}^{-}) \tag{9}$$

If the first step is essential and therefore rate-controlling, then the electron affinity of the substrate is an important consideration. Thus, CB (*E*<sup>A</sup> = �0.14 eV) is less reactive than hexachlorobenzene ((HCB) with *E*<sup>A</sup> = +0.94 eV). Since the electron transfer process (Eq. (8)) occurs with much difficulty, unmodified nZVI is not suitable for the reduction of aromatic C–Cl bonds attached to aromatic structures [24, 25]. Both Cu and Pd are able to reduce C–Br and C–Cl bonds attached to aromatic structures, and the reaction rates are substance- and system-specific. Under similar reaction conditions and for nanoparticles with comparable sizes, Shee (2021) determined that the *<sup>A</sup>*Cu for dehalogenation of CB and BB were (*A*Cu,CB = (4 � 1) � <sup>10</sup>�<sup>5</sup> L/ (g�min)) and (*A*Cu,BB = (8 � 1) � <sup>10</sup><sup>1</sup> L/(g�min)), respectively. In the same study, Pd activities were the highest where *<sup>A</sup>*Pd,CB = (5 � 1.5) � 102 L/(g�min) and *<sup>A</sup>*Pd, BB = (9 � 1) � <sup>10</sup><sup>2</sup> L/(g�min). Therefore, Cu which is cheaper and stable in water can be applied as the "agent of choice" for the treatment of brominated aromatic compounds. The niche application of protected Pd catalyst is seen only in *ex situ* treatment of chlorinated aromatics such as in soil washing and pump and treat technologies.

### **5. Future perspectives and application areas of the CBHS**

The CBHS has shown potential for use in water treatment technologies for a broad range of compounds. However, the technology is still in its initial stages, and there are still some aspects that need further investigation. First, the possible reductants either hydrides or H\* need to be clarified in order to explain the difference in reactivity between halogenated alkanes and alkenes.

Since BH4 � is used as a reductant, clarification on the exact number of H-atoms (hence electrons) transferred to the contaminant is essential. This clarification is needed for the evaluation of reductant costs. Based on reduction equivalents and unit prices of the reductants, it was estimated that NaBH4 costs more than H2 by at least a factor of 12 [36].

The comparison of the HDH ability of Cu and Pd has been investigated using two different reductants and in the aqueous phase where a layer of the solvent is introduced around the metal particles. Although nanosized particles were applied and the batch reactors were continuously shaken, mass transfer limitations especially for fastreacting substances need consideration. For better comparison, we suggest experiments carried out under similar elevated temperature conditions, and that H2 is used as a reductant. The HDH reactions are then conducted in the gaseous phase at hot solid metal catalysts (Cu and Pd).

*Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters DOI: http://dx.doi.org/10.5772/intechopen.108147*

Another challenge is connected with effluents at pH values between 9 and 10 when BH4 is applied as a reductant, as well as the formation of the undesired borates and boric acid [36]. Removal of boric acid and borates may be necessary before the effluent is discharged.

Trace amounts of Cu are essential for the functioning of various biological processes in humans, plants, and animals. Nevertheless, higher Cu doses are toxic [86]. Therefore, the leaching of Cu into the environment must be controlled. Simple iron beds are effective police filters. Embedding Cu onto cation-exchange resins was also seen to minimize Cu leaching after repeated reaction cycles [36, 87]. Amberlite IRP 69 as support for Cu does not only offer partial protection of the catalysts against S2 but also enables regeneration of the deactivated catalyst simply by washing with water [36]. Apart from cation-exchange resins, other adsorbents such as zeolites may be investigated. The speciation of Cu within these adsorbents and the role of the support on catalyst performance are possible topics for further research. Since contact between the embedded Cu and BH4 may not be possible, it is also necessary to identify the nature of reducing species that facilitate the HDH reaction.

### **6. Conclusions**

This chapter shows that CBHS although has received less attention should be considered as an alternative tool to nZVI and Pd in water treatment applications. The high potential of the CBHS is seen in the *in situ* regeneration of HOCs-loaded adsorbents in small-scale treatment plants. For detoxification of contaminated soils, preliminary processes including soil washing, filtration, adsorption, and desorption should be implemented in the initial stages to transfer immobilized HOCs into an aqueous media. The CBHS can then be added into the HOCs concentrated aqueous media for detoxification.

### **Acknowledgements**

The authors would like to sincerely thank DAAD (German Academic Exchange Service) for funding a scholarship to A. Shee.

### **Conflict of interest**

The authors declare no conflict of interest.

## **Author details**

Ali Shee and Katrin Mackenzie\* Department of Environmental Engineering, Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany

\*Address all correspondence to: katrin.mackenzie@ufz.de

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Metallic Copper as Dehalogenation Catalyst in the Treatment of Water and Wastewaters DOI: http://dx.doi.org/10.5772/intechopen.108147*

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### **Chapter 5**

## Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small Biomolecules

*Azadeh Khanmohammadi*

### **Abstract**

In this chapter, the influence of non-covalent interactions on the complexes formed by the various biomolecules (mesalazine, para-aminosalicylic acid, acetaminophen, psoralen, and methyl salicylate) with the Cu2+ cation is investigated using the density functional theory (DFT) method. Since the interactions involving aromatic rings are crucial binding forces in chemical systems, this is exciting research trying to understand and control the effect of non-covalent interactions responsible for complicated functions in nature. Herein, the calculations are performed in the gas phase and water solvent. The results show that the absolute amounts of energy are reduced by going from the gas phase to the solution. The topological properties of the electron density and the values of charge transfer are evaluated by the Bader theory of atoms in molecules (AIM) and the natural bond orbital (NBO) analysis, respectively. These results are useful for understanding the role of the drug-receptor interactions in the complexes. The electronic descriptors are also important factors in forming a charge-transfer complex between cation and biological target. The results of this study that are ubiquitous in biological systems may be useful for the design and synthesis of a variety of supramolecular complexes with the desired properties.

**Keywords:** non-covalent interactions, DFT, AIM, NBO, HOMA

### **1. Introduction**

Para-aminosalicylic acid (PAS) or 4-aminosalicylic acid (brand name Paser) is an antituberculosis antibiotic [1]. It is applied in combination with other antituberculosis drugs, such as isoniazid, thiacetazone, and streptomycin [2]. PAS inhibits the folic acid synthesis and is the second antibiotic useful in the treatment of tuberculosis after streptomycin [3]. In 1948, researchers demonstrated that combined treatment with streptomycin and PAS was superior to either drug alone, and established the principle of combination therapy for tuberculosis [4]. Mesalazine (MES) or 5-aminosalicylic acid (also known as mesalamine) is an intestinal aminosalicylate drug [5]. This drug is very useful for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease [6]. The MES is similar to salicylates, but it is structurally and therapeutically different from 4-aminosalicylic acid (or p-aminosalicylic acid). Methyl salicylate (MS) is chemically known as methyl-2-hydroxybenzoate, wintergreen oil, and betula oil, which has the empirical formula C8H8O3. MS is pharmacologically similar to aspirin and has anti-inflammatory properties [7]. It is used as a rubefacient and analgesic in the treatment and temporary management of aching and painful muscles and joints [8].

Psoralen (PSO) is naturally synthesized in the form of tricyclic aromatic compounds, which is obtained by compressing a coumarin nucleus with a furan ring [9]. Since its chemical structure is similar to coumarin, it is used in the treatment of some cancers, including T-cell lymphomas in patients with AIDS [10]. It can also be utilized to treat hyperproliferative skin disorders such as psoriasis, eczema, vitiligo, and certain types of skin cancer [11]. Acetaminophen (AC) or N-acetyl-p-aminophenol (with trade names of Tylenol and Panadol) is one of the most popular and most generally applied painkillers and antipyretic drugs around the world. It has relatively low antiinflammatory activity [12] with respect to other drugs, such as aspirin and ibuprofen. It increases the pain threshold by blocking an enzyme called cyclooxygenase (COX) [13, 14].

The non-covalent interactions (NCIs), such as hydrogen bonding, halogen bonding, and cation-π, anion-π and π-π interactions, are very important in supramolecular chemistry, drug design, protein folding, and crystal engineering [15, 16]. The hydrogen bond (HB) is the most popular form of NCI that directs many chemical, physical, and biochemical processes [17]. The HB interaction is designated as XdH⋯Y, in which XdH and Y are the proton-donor and proton-acceptor groups, respectively. Since the hydrogen atom has only one orbital (1s) with sufficiently low energy, HBs are predominantly electrostatic in nature, but covalent and repulsive orbital-orbital interactions are also present. Depending on the type of X and Y, there are strong and weak HBs. In the case of weak HBs, the respective bonding is mainly electrostatic in nature with attractive and repulsive charge-charge, charge-dipole, charge-induced dipole, and charge-multipole interactions between the partially positive charged hydrogen atom and the negatively charged areas of the Y acceptor atom. In the case of strong HBs, in addition to the Coulomb forces, the phenomena of covalent bonding through orbital-orbital overlap attractive and closed-shell repulsive forces are of particular importance.

The cation-π interactions, as another ensemble of NCIs, are significant in biological structures and molecular recognition processes [18]. These interactions represent a strong attraction between the cations and the π-system. The electrostatic and induction interactions are mainly responsible for the attraction. The electrostatic interaction is between the quadrupole of the π-system and the charge of the cation [19]. The magnitude of the induction interaction is proportional to the square of the electric field produced by the cation [20]. Thus, the cations with greater charge have large induction energies.

The importance of cation-π interactions and their physical origin is also vital for understanding the structures and properties of molecular assemblies, improving material and drug design strategies [21]. For example, the role of cation-π interactions in the stability and design of peptides was investigated in 2001 [22]. In this study, the cation-π interactions between amino acid side chains are increasingly recognized as important structural and functional features of proteins and other biomolecules. It is also generally understood that helical proteins are stabilized by a combination of

*Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

hydrophobic and packing interactions, together with H-bonds and electrostatic interactions. In 2001 [23], Kallenbach et al. showed that polar side-chain interactions on the surface can play an important role in helix formation and stability.

Interactions of metals with biomolecules play an important role in pharmaceutical chemistry [24] through "classical" organometallic chemistry to environment protection (metal-binding biomass) [25]. The role of metal ions in the structure and function of proteins, nucleic acids, and peptide hormones is essential. The pharmacology of metal-drug interactions may depend on the method of management. A metal-drug complex can be directed as a therapeutic agent, or the drug can be administered and interact with metal ions in the body. In addition, the application of drugs in chelating with metal ions or change in the polarity of the medium may affect their chemical and biological properties [26, 27].

Complexes obtained from M (II) ions with strong bioactive ligands containing N and O donor binding sites are employed for biological, analytical, agricultural, industrial, and medicinal purposes [28]. Metal ions are the ultimate components of a healthy life for humans and animals [29]. Copper (Cu) is biologically an appropriate metal associated with different biomolecules due to crucial physiological activities, and it is an important suggestion element for many biological functions [30]. For example, the biological activities of the isolated metal chelates were screened against different types of bacteria and fungi. Rayan et al. [31] showed that the cetirizine drug and the complexes inhibited the growth of tested bacteria to varying degrees, more pronounced when coordinated with the metal ions.

Cu (II) shows an essential character for improving connective tissue, nerve coverings, and bone in humans. The Cu (II) complexes with their bioessential activity and oxidative nature are applied in various biological activities, including antibacterial [32], antitumor [33], antifungal [34], antioxidant [35], and anti-inflammatory [36]. Due to the biological importance of copper cation, it is necessary to consider complexation with bioactive ligands to identify the function of their complexes and to discover new bioactive compounds.

The main purpose of this study is to analyze the effects of NCIs on the energetic, geometric, topological, charge transfer, and electronic descriptors of considered complexes. For this goal, DFT calculations and AIM and NBO analyses are carried out on the MES, PAS, AC, PSO, and MS biomolecules with Cu2+ cation. Furthermore, the effect of these interactions on the aromaticity of the complexes is evaluated by calculating the geometry-based HOMA aromaticity index. In order to deal with this issue in depth, we present an inclusive analysis of the interactions mentioned in the electronic properties of the studied complexes. It should be declared that the importance of theoretical models for these interactions in biological systems has allowed us to study them.

### **2. Computational procedures**

In this study, all calculations are implemented with the Gaussian 09 suite of programs [37]. The geometry optimization is performed at the wB97XD/6-311++G(d,p) level of theory in the gas phase and water solvent. The used basis set is of triple-ζ quality [38] for valence electrons with diffuse functions, which are suitable in computations for ions and structures with lone-pair electrons [39]. The calculations of frequency are carried out at the same level to verify that these structures are local minima on the energy surfaces. The solvent effect for the water solution is obtained using the polarizable continuum model (PCM) [40]. The binding energy with

correction for the basis set superposition error (BSSE) is calculated using the Boys-Bernardi counterpoise technique [41] as follows:

$$
\Delta \mathbf{E} = \mathbf{E}\_{\text{cation}-\pi} - \left(\mathbf{E}\_{\text{cation}} + \mathbf{E}\_{\pi-\text{system}}\right) + \mathbf{E}\_{\text{BSSE}} \tag{1}
$$

According to this formula, Ecation-<sup>π</sup> is the total energy of the complexes and Ecation and Eπ-system are the total energies of the free cation and the π-systems, respectively. The stability of the complexes in the presence of water solvent is investigated, and their results are compared with the gas phase. The stabilization energy (Estab) can be calculated from the total energies at the same level of theory as follows:

$$\mathbf{E\_{stab}} = \mathbf{E\_{tot}} \left( \text{solvent} \right) - \mathbf{E\_{tot}} \left( \mathbf{gas} \right) \tag{2}$$

where Etot (solvent) and Etot (gas) are the total energy of the complexes in the presence and absence of solvent, respectively. The topological electron charge density is analyzed by the atoms in molecules (AIM) method [42]. The natural bond orbital (NBO) analysis [43] is used to determine the direction and magnitude of donoracceptor interactions. The AIM and NBO calculations are carried out with the AIM2000 [44] and NBO programs [45] under the Gaussian 09 program package, respectively. The harmonic oscillator model of aromaticity (HOMA) [46] index is applied as a geometric criterion of local aromaticity according to the formula suggested by Kruszewski and Krygowski [47]:

$$\text{HOMA} = \mathbf{1} - \frac{a}{n} \sum\_{i=0}^{n} \left( R\_{opt} - R\_i \right)^2 \tag{3}$$

where n is the number of bonds within the investigated rings, α is a constant, and Ropt and Ri are the optimal values of bond lengths for ideally and studied aromatic

*Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

**Figure 1.** *The model representation for the PSOM (a), ACM (b), PASM (c), MESM (d) and MSM (e) complexes, with M = Cu2+ from front and top views.*

systems. In this research, the Ropt and α are estimated at the wB97XD/6-311++G(d,p) level of theory (for CC and CO bonds: Ropt,CC = 1.393 Å, Ropt,CO = 1.270 Å, αCC = 89.34, αCO = 77.22). Here, HOMA = 1 is ideal for aromatic systems and HOMA = 0 is for nonaromatic species. Finally, the molecular orbital calculations, such as the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies, are performed on the explored systems.

### **3. Results and discussions**

In this work, the effects of NCIs on the different biomolecules of MES, PAS, AC, PSO, and MS with Cu2+ cation (**Figure 1**) are investigated. As shown in these Figures, the PSO and AC complexes have only the cation���π interaction, while the PAS, MES, and MS complexes have the two NCIs of cation���π and intramolecular hydrogen bond (IMHB) in their structure.

### **3.1 Energetic descriptors**

The binding energies corrected with BSSE (ΔEion-π) of the complexes are listed in **Table 1**. It is well known that the strength of the cation���π interactions strongly depends on the physical properties of the cations and the π-system, the solvation effects, and the interaction geometry. The results show that the obtained absolute values of ΔEion-<sup>π</sup> in the gas phase and water solvent are arranged in MES > PAS > AC > PSO > MS order. It is obvious that these values decrease with going from the gas phase to the solution. For example, the binding energy of the MES⋯Cu2+ complex reduces from �259.87 kcal/mol in the gas phase to �101.24 kcal/ mol in the water solvent. However, as shown in **Table 1**, the highest and lowest values of ΔEion-<sup>π</sup> in both the gas phase and solution belong to the MES and MS complexes, respectively.

The IMHB energy of the complexes is estimated by means of the Espinosa method [48]. The potential and kinetic energy densities can be determined from the following equations:

$$\mathcal{G}(r\_{\rm CP}) = \left(\frac{3}{10}\right) \left(3\pi^2\right)^{\frac{2}{3}} \rho^{\frac{5}{3}}(r\_{\rm CP}) + \left(\frac{1}{6}\right) \nabla^2 \rho(r\_{\rm CP}) \tag{4}$$

$$V(r\_{CP}) = \left(\frac{1}{4}\right)\nabla^2\rho(r\_{CP}) - 2G(r\_{CP})\tag{5}$$


where G(r) is the kinetic energy density, V(r) is the potential energy density, and ρ(r) and ∇<sup>2</sup> ρ(r) are the electron density and its Laplacian at the critical point (CP),

### **Table 1.**

*The BSSE-corrected binding and IMHB energies (ΔEion-<sup>π</sup> and EHB, in kcal mol*�*<sup>1</sup> ), total energy (Etot, in eV), stabilization energy (Estab, in eV), relative energy (Erel), and thermodynamic parameters of complex formation in the gas phase and water solvent (ΔH, ΔG, and ΔS, in kcal mol*�*<sup>1</sup> ).*

*Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

respectively. The simple relationship between the HB energy (EHB) and the potential energy density V(rcp) at the critical point corresponding to the H⋯O contact is assigned to be as follows [49]:

$$E\_{HB} = \frac{1}{2} \left| V(r\_{CP}) \right. \tag{6}$$

According to the results, the order of EHB for the selected complexes in the gas phase and in water is PAS > MS > MES and PAS > MES > MS, respectively (see **Table 1**). As shown in this table, the strongest HB is related to the PAS complex, and the EHBs obtained in both the gas phase and solution for the MES and MS complexes are close to each other and lower than the PAS complex.

The values of total energy (Etot), stabilization energy (Estab), and relative energy (Erel) of the complexes are listed in **Table 1**. The calculations show that the PSO and AC complexes have the most and least stability in the gas and water phases, respectively. The structure's stability according to the total energy in the gas phase and solution obeys the following order: PSO > MES > PAS > MS > AC. There is a good linear relationship between the total energy (Etot) and the dipole moment (μ°) of the complexes in the water solvent (see **Figure 2**). This correlation displays that increasing stability is associated with enhancing dipole moment. For the studied complexes, the Estab values follow the MS > AC > MES > PSO > PAS order. In water solvent, the Estab of MS complex is the highest and the lowest value is related to the PAS complex. The results also show a similar trend for the relative energies obtained in the analyzed complexes. **Figure 3** illustrates the stability diagram of different biomolecules in terms of relative energy (Erel) in the gas and water phases. It is clear that the stability changes depend on the dielectric constant. In other words, with increasing dielectric constant, the stability enhances.

To achieve better insight into the mentioned interactions, we have calculated the Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) thermodynamic changes at 298.15 Kelvin and 1 atmosphere, which are obtained from the frequency calculations. The results are collected in **Table 1**. As shown in this Table, in most cases, the calculated ΔH values for the complexes are negative and the ΔG values are positive (see **Table 1**). The negative ΔH values reveal that the formation of these complexes is enthalpically favorable. It is well known that the complexes with lower/higher ΔG values are relatively more stable/unstable, respectively. Nevertheless, the smaller

**Figure 2.** *Correlation between the total energy (Etot) and dipole moment (μ°) in water solvent.*

**Figure 3.** *Chart of the stability order in terms of relative energy (Erel) in gas phase and water solvent.*

values of ΔH compared to those of ΔG are due to the entropic effect. This means that the ΔS values are negative in all cases studied, and the TΔS values indicate the large entropy changes during the formation of complexes. Since the selected complexes in water solvent are more stable than in the gas phase, in most cases the complexes of this phase are described with higher ΔH values.

### **3.2 Geometric descriptors**

In the selected complexes, after optimizing the geometry, the cations do not remain exactly along the perpendicular symmetric axis of the benzene ring and approach to the ring bonds. It seems that the deviation of cations from the symmetric axis of the benzene ring can be related to the more negative electronic charge of the C5–C6 bond. In the PAS complex, the cation approaches the C6 position. **Table 2** presents the geometrical parameters of the complexes formed between the Cu2+ cation


### **Table 2.**

*The geometrical parameters (bond lengths (d), in Å and bond angles (θ), in °), HOMA values, and dipole moment (μ° in Debye) of complexes calculated at the wB97XD/6-311++G(d,p) level of theory.*

*Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

and the different π-systems. The strength of the cation-π interactions can be described by the distance between the cation and the benzene ring (d<sup>π</sup>M). Theoretical results show that the stronger cation-π interaction is associated with the smaller d<sup>π</sup><sup>M</sup> and *vice versa* (except for the MES complex). The minimum and maximum values of d<sup>π</sup><sup>M</sup> in the gas phase and water correspond to the PAS and MS complexes, respectively.

The HB is the most common form of NCIs, which is formed between a hydrogen atom attached to an electronegative donor atom and an adjacent acceptor atom. In this chapter, the strength of the IMHB can change with the geometric parameters of the OdHO unit. The values of bond lengths and their corresponding angles are given in **Table 2**. The obtained results show that in most cases, in both phases, with increasing the strength of HB, the OdH bond length (dO-H) and the OHO angle (θOHO) increase and the OO (dO … O) and HO (dH … O) distances decrease. The OdH proton donor bond is usually stretched due to HB formation, and this elongation is greater for stronger HBs. The shorter the H⋯O distance, the stronger the HB. These results are consistent with the calculated HB energies.

The structure, reactivity, and stability of the cyclic organic molecules can be determined by aromaticity indices. The geometric parameters of the rings (CC and CO bond lengths) are applied to estimate the so-called geometrical indices of aromaticity based on the HOMA model [41]. This index is used to assess the aromaticity of the benzene ring and the quasi-ring of the OdHO unit. The data in **Table 2** indicate that the HOMA index of the complexes in the gas and water phases is in the range of 0.821–0.901. Our results display that the maximum and minimum HOMA values of the HB unit are related to the MES and MS complexes, respectively. Based on the calculated data, the complexes in the gas phase have the least aromaticity, while the most aromaticity belongs to the water solvent (see **Table 2**). In fact, higher HOMA values can be attributed to more electron delocalization. Hence, the greater stability of


**Table 3.**

*The selected topological properties of electron density (in a.u.) obtained by AIM analysis.*

the complexes in the water solvent is due to their more electron delocalization in this solvent.

The dipole moment of the complexes (μ°) in the gas and solution phases is reported in **Table 2**. Dipole moment can be used as a descriptor to represent the motion of a charge across a molecule. Direction of the dipole moment vector in a molecule depends on the centers of positive and negative charges. The computations offer that the difference between the dipole moments can be related to the values of the charge on the metal cation and environmental factors. It is obvious that the PSO complex has the largest dipole moment, while the smallest value is observed in the AC complex. This may be expressed by considering the amount of charge on the Cu2+ cation of the complexes. It is worth mentioning that in the PSO complex, the Cu2+ cation has the highest positive charge, while there is less positive charge on the Cu2+ cation in the AC complex. According to the obtained results, the dipole moment values of the analyzed complexes in the water solvent are higher than their corresponding values in the gas phase.

### **3.3 Topological descriptors**

In order to explore the nature and strength of NCIs in the selected biomolecules, AIM analysis is performed. The charge density, ρ(r), Laplacian of electron density, ∇2 ρ(r), total electron energy density, H(r), and its components (G(r) and V(r)) at the bond critical point (BCP) are utilized to obtain the topological parameters of the studied complexes. The sign of ∇<sup>2</sup> ρ(r) is used to recognize closed-shell and sharedshell interactions. The values of ∇<sup>2</sup> ρ(r) < 0 exhibit shared-shell interactions in covalent forces, while the values of ∇<sup>2</sup> ρ(r) > 0 indicate closed-shell interactions in HBs, ionic bonds, and van der Waals forces [50]. The molecular graphs of complexes analyzed using the AIM2000 program package are illustrated in **Figure 4**.

According to the results of AIM analysis obtained in **Table 3**, the electron density properties calculated for the complexes show that π⋯M bonding has low ρ(r) (ranging from 0.0682 to 0.0804) and positive ∇<sup>2</sup> ρ(r) values (ranging from 0.1644 to 0.2164) but the corresponding H(r) values are negative (ranging from 0.0176 to 0.0286). These data indicate that the cation-π interactions in the selected systems are at least partially covalent in nature. Our findings in **Table 3** show that the order of the ρπ⋯<sup>M</sup> values for the complexes in the gas phase and in water is PAS > MES > PSO > AC > MS and PAS > MES > MS > AC > PSO, respectively. As observed, the highest value of ρπ⋯<sup>M</sup> in both phases belongs to the PAS complex. Contrary to the calculated binding energies, it is evident in **Table 3** that the obtained values of ρ(r) and ∇2 ρ(r) increase with going from the gas phase to the solution (except for the PAS complex).

The formation of HB in the complexes is confirmed with the presence of a bond critical point between the hydrogen atom of the donor group and the acceptor atom. The calculated topological parameters are given in **Table 3**. As can be seen in this table, the electron density of the H⋯O contact at BCP (ρ<sup>H</sup> … O) for the PAS complex is higher than the other ones in both the gas phase and the solution. It is also clear that the values of ρ<sup>H</sup> … <sup>O</sup> and ∇<sup>2</sup> ρ<sup>H</sup> … <sup>O</sup> calculated in the gas phase are larger than the water solvent. Furthermore, the values of ∇<sup>2</sup> ρ(r) > 0 and H(r) < 0 show that the HB interaction of the complexes is in the category of medium HBs. The –G/V ratio can also be exploited as a criterion for the character of NCIs [51, 52]: for –G/V > 1, and the interaction is electrostatic, while for 0.5 < G/V < 1, it is partially covalent. The

*Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

**Figure 4.** *The molecular graphs of PSO (a), AC (b), PAS (c), MES (d) and MS (e) complexes explored in this study.*

results obtained in **Table 3** show that the NCIs in the systems under study are partially covalent.

### **3.4 Charge transfer descriptors**

The NBO analysis explores the orbital interactions and the charge transfer values of the complexes [43]. The stabilization energy (E(2)) estimated by the second-order perturbation theory, the occupation numbers of donor (OND) and acceptor (ONA) orbitals, and the values of charge transfer (ΔqCT) are given in **Table 4**. The NBO


### **Table 4.**

*The values of E(2) correspond to <sup>π</sup>(C–C)* ! *LP\*(M) and LP(O)* ! *<sup>σ</sup>\*(O–H) interactions (in kcalmol*�*<sup>1</sup> ), occupation numbers of donor (OND) and acceptor (ONA) orbitals, oxygen atomic charges (q(O)), and the charge transfers (Δq(CT) in e) in the studied complexes.*

analysis is performed to evaluate the intermolecular interactions between biomolecules and the Cu2+ cation. The results indicate a charge transfer from π-system of the donor species (πC–C) to the LP\*(M) (an "empty" lone pair of cation) as acceptor species (π(C–C) ! LP\*(M)). As shown in **Table 4**, the maximum and minimum values of E(2) in the gas phase belong to the MES and MS complexes, respectively, which correspond to their binding energies. In addition, despite the obtained binding energies, the donoracceptor energy of the cation-π interaction increases on passing from the gas phase to the solution phase.

The results of the NBO analysis for HB interaction indicate that the lone pairs of oxygen (LPO) as donor and antibonding orbital of OdH (σ\*O–H) as acceptor provide high stability in the complexes (LP(O) ! σ\*(OdH)). As can be seen in **Table 4**, the greatest values of E(2) are related to the gas phase, while the smallest values correspond to the water solvent. The trend of these results is similar to the obtained HB energies. An increase in the occupancy number of the σ\*(O<sup>d</sup>H) antibond orbital (ONσ\*O<sup>d</sup>H) and further weakening and lengthening of the OdH bond can be observed in HB systems. Inspection of **Table 4** reveals that the highest values of E(2) and ONσ\*Od<sup>H</sup> and the lowest values of ONLP(O) in both the gas phase and solution belong to the PAS⋯Cu2+ complex. This means that the HB is stronger in this complex compared with the others. Consequently, the changes in the occupation numbers of the LP(O) (ONLPO) and σ\*(O<sup>d</sup>H) (ONσ\*O<sup>d</sup>H) are in agreement with the energy of charge transfer from LP(O) to σ\*(O<sup>d</sup>H) (E<sup>2</sup> ) and the HB formation energy (EHB) (except for the MS complex in the gas phase).

The charge transfer is a significant aspect in determining donor and acceptor species. The change of charges leads to charge transfer and molecular polarization in the interaction process. From the difference between the cation charges in the

complex state and the free state, the values of charge transfer (ΔqCT1) between the biomolecule rings and the Cu2+ cation are obtained. The results of **Table 4** show that the most/least values of Δq(CT1) are related to complexes in the gas phase/solution, respectively.

In the NBO analysis of HB systems, the charge transfer between the lone pairs of proton acceptor and antibonds of the proton donor is the most important. The charge transfer (ΔqCT2) for these systems is determined by the difference between the atomic charges of oxygen in the complexes and their corresponding monomers as: Δq(CT2) = qO (complex) � qO (monomer). As observed in **Table 4**, the highest absolute values of Δq(CT2) are observed in the gas phase and the lowest values are obtained in the water solvent, which in most cases correspond to their values of E(2).

### **3.5 Electronic descriptors**

The frontier molecular orbitals (FMOs) are investigated to evaluate the stability and reactivity of the studied biomolecules. The significant FMOs usually express the chemical behavior of complexes. The important concepts in quantum chemistry are the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), and its energy gap. **Figure 5** illustrates the plots of the HOMO and LUMO orbitals of the selected complexes in the gas phase as obtained at the wB97XD/ 6-311++G(d,p) level of theory. In the corresponding diagrams, the red and green colors denote the positive and negative phases, respectively.

Some chemical concepts, such as energy gap (Eg), chemical potential (μ) [53], global hardness (η) [54], electrophilicity index (ω) [55], global softness (S), and electronegativity (χ) [56], are reported in **Table 5**. These quantities are identified as descriptors of chemical reactivity that are determined from the orbital energies of HOMO and LUMO based on the equations of Koopman's theorem [57]. The chemical potential and chemical hardness are the first and second partial derivatives of E[ρ], respectively, with respect to the number of electrons under the constant external potential, which are given below:

$$
\mu = \left(\frac{\partial \mathbf{E}}{\partial \mathbf{N}}\right)\_{\mathbf{V}(\mathbf{r}), \mathbf{T}} \tag{7}
$$

$$\eta = \left(\frac{\partial^2 \mathbf{E}}{\partial \mathbf{N}^2}\right)\_{\mathbf{V}(\mathbf{r}), \mathbf{T}}\tag{8}$$

$$\mathbf{S} = \frac{1}{2\eta} \tag{9}$$

$$
\alpha = \frac{\mu^2}{2\eta} \tag{10}
$$

The softness (S) is a key factor in the study of the polarizability of molecules [58], and the electrophilic nature of a molecule is expressed by the electrophilicity index.

It is apparent that the larger values of Eg and η display higher molecular stability and lower reactivity in chemical reactions [59]. Inspection of **Table 5** shows that the values of Eg increase in the following order MS > PAS > AC > MES > PSO. As can be seen, the hardest and the most stable system belongs to the MS complex, while the softest and the most reactive system corresponds to the PSO complex. From the results of **Table 5**, it can be observed that the values of the electronic chemical

**Figure 5.**

*HOMO and LUMO plots of PSO, AC, PAS, MES and MS complexes obtained at the wB97XD/6-311++G(d,p) level of theory.*


*Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

### **Table 5.**

*Values of the HOMO and LUMO energies (EHOMO and ELUMO), energy gap (Eg), chemical hardness (η), softness (S), electronic chemical potential (μ), electronegativity (χ), and electrophilicity index (ω).*

potential are negative. This indicates that all complexes are stable. The electronegativity (χ) is defined as the negative of μ, as follows: χ = μ. Our findings display that the maximum and minimum values of electronegativity correspond to the MS and AC complexes, respectively. The trend in the values of electrophilicity index is PSO > MS > MES > AC > PAS. As it is obvious, the maximum electrophilicity index is accompanied by the minimum value of Eg. This is due to the higher electron flow between the HOMO and LUMO orbitals in the related complex.

Molecular electrostatic potential (MEP) surfaces show the three-dimensional charge distributions of molecules. Different colors are used to represent the values of the surface electrostatic potentials. The red and blue regions in the MEP map are related to the electron-rich and electron-poor areas, respectively, while the green color implicates the neutral electrostatic potential. **Figure 6** illustrates the electron density isosurface mapped with the electrostatic potential surface for the complexes selected in this study. As can be seen from the MEP map of these complexes, while the regions

### **Figure 6.**

*Electron density isosurface for PSO, AC, PAS, MES and MS complexes calculated by wB97XD method and 6-311 ++G(d,p) basis set.*

having the negative potential are over the oxygen electronegative atoms (red and yellow colors), the regions having the positive potential are over the Cu2+ cation and the benzene ring plane (blue color).

### **4. Conclusion**

In this study, the influence of NCIs on the complexes formed by the various biomolecules (MES, PAS, AC, PSO, and MS) with the Cu2+ cation is investigated using the DFT method. The results show that the absolute values of ΔEion-<sup>π</sup> are arranged in MES > PAS > AC > PSO > MS order. It is obvious that these values decrease with going from the gas phase to the solution. For the studied complexes in water solvent, the Estab of MS complex is the highest and the lowest value is related to the PAS complex. From the HOMA results, it can be understood that the greater stability of the complexes in the water solvent is due to their more electron delocalization in this solvent. Contrary to the calculated binding energies, it can be seen that the values of ρ(r), ∇<sup>2</sup> ρ(r), and the donor-acceptor energy increase on passing from the gas phase to *Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

the solution. The formation of HB in the complexes is confirmed with the presence of a bond critical point between the hydrogen atom of donor group and the acceptor atom. The strongest HB is related to the PAS complex, and the EHBs obtained for the MES and MS complexes are close to each other. Furthermore, the values of ∇<sup>2</sup> ρ(r) > 0 and H(r) < 0 show that the HB interaction of the complexes is in the category of medium HBs. Our data also display that the greatest values of E(2) are related to the gas phase, while the smallest values correspond to the water solvent. The trend of these results is similar to the obtained HB energies. The frontier molecular orbital analysis shows that the hardest and the most stable system belongs to the MS complex, while the softest and the most reactive system corresponds to the PSO complex.

### **Acknowledgements**

The author wishes to thank the Payame Noor University, Tehran, Iran for its support.

### **Conflict of interest**

The author has no conflict of interest.

### **Abbreviations**


### **Author details**

Azadeh Khanmohammadi Department of Chemistry, Payame Noor University, Tehran, Iran

\*Address all correspondence to: az\_khanmohammadi@yahoo.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Investigation of Non-Covalent Interactions of Copper (II) Complexes with Small… DOI: http://dx.doi.org/10.5772/intechopen.106216*

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### **Chapter 6**
