# Molecular Design of Novel Chemicals for Iron Sulfide Scale Removal

Authors: Abdulmujeeb T. Onawole; Ibnelwaleed A. Hussein; Hassan I. Nimir; Musa E. M. Ahmed; Mohammed A. Saad
Journal: Journal of Chemistry
 (2021)

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## Abstract

Scale deposition is a pertinent challenge in the oil and gas industry. Scales formed from iron sulfide are one of the troublous scales, particularly pyrite. Moreover, the use of biodegradable environmentally friendly chemicals reduces the cost compared to the conventional removal process. In this work, the chelating abilities of four novel chemicals, designed using thein silico technique of density functional theory (DFT), are studied as potential iron sulfide scale removers. Only one of the chemicals containing a hydroxamate functional group had a good chelating ability with Fe2+. The chelating strength and ecotoxicological properties of this chemical were compared to diethylenetriaminepentaacetic acid (DTPA), an already established iron sulfide scale remover. The new promising chemical surpassed DTPA in being a safer chemical and having a greater binding affinity to Fe2+ upon optimization, hence, a better choice. The presence of oxime (-NHOH) and carbonyl (C=O) moieties in the new chemical showed that the bidentate form of chelation is favored. Moreover, the presence of an intramolecular hydrogen bond enhanced its chelating ability.


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## Body

## 1. Introduction

Scale deposition is a cogent problem facing oil and gas production. Scales formed from iron sulfide are one of the troublous scales, particularly pyrite [1, 2]. Other types of scales include calcium carbonates and sulfates, barium sulfate, and strontium sulfate. The costs related to scale deposition were estimated to be about 800 million $US in the United Kingdom, 9 billion $US in the USA, and 3 billion $US in Japan while the global cost amounted to about 2.5 trillion $US [3, 4]. The reaction of iron and hydrogen sulfide forms the iron sulfide scale. The former occurs in the oil and gas production system including pipes, reservoirs, and wellbore tubular. Hydrogen sulfide, on the other hand, is found in sour gas wells as free gas and sometimes it evolves during the degradation of organic sulfur-containing chemicals due to the presence of sulfate-reducing bacteria [5, 6].Conventional treatments used in iron sulfide scale removal include chemical and mechanical treatments [7]. Nevertheless, the former is preferred over the latter as mechanical treatment frequently exacerbates the situation by leading to more corrosion. On the other hand, chemical treatments involving the use of hydrochloric acid increase the corrosion rate and also produce toxic hydrogen sulfide as a by-product. Chelators have been suggested as a better chemical solution for scale removal [8–12]. Diethylenetriaminepentaacetic acid (DTPA) is one of the effective chelators used for iron sulfide scale removal [1, 2]. However, there is a need to develop novel biodegradable chelators. Hence, in this work, we design novel chemicals based on the hydroxamate functional group and also the carboxylic functional group present in DTPA.Siderophores are naturally occurring low molecular weight chelators containing catecholate and hydroxamates moieties. They are known to form one of the strongest iron-chelating complexes and used by microorganisms to sequester iron [13, 14]. Hydroxamates features the general formula-R(C=O)NHOH, where R could be an alkyl or aryl group. The –(C=O)NHOH moiety is the key functional group binding to iron and hence has been developed and applied in medicine in treating cardiovascular diseases, metal poisoning, and overload of iron and anticancer and antitumor agents [15–18]. Other applications are extended to corrosion inhibition, mineral floatation, and extraction of toxic metals [19, 20]. The –(C=O)NHOH can be divided into the carbonyl group (C=O) and the oxime group (NH-OH). This enables hydroxamates to act as either a monodentate or bidentate and or/bridging ligand when binding to a metal ion. The configuration depends on whether one of the oxygen atoms (monodentate) or both (bidentate) oxygen atoms in the carbonyl and oxime group are used in bonding. Also, hydroxamates have the ability to form both intra- and interhydrogen-bonds which enhances their chelating ability.Molecular design methods, particularly density functional theory (DFT), have become a widely used tool in understanding the molecular structure of various molecules, including inorganic chemicals [21, 22]. Also, it has been used to design novel chemicals never before synthesized as it saves the cost of trial and error compared to wet labs concerning time and chemicals [23, 24]. However, despite the applications of hydroxamates, there is a dearth of literature on theoretical studies of hydroxamates, and this is due to the challenge in modeling transition metal complexes [15, 19]. Nevertheless, DFT has been used in studying transition metal complexes [25, 26]. Herein, we study four novel chemicals having to contain hydroxamic and carboxylic acid functional groups and analyze their chelating ability to Fe2+, which is the state of iron in the pyrite scale. Our previous works which include both experimental [27] and theoretical studies [28] showed that borax is an effective iron sulfide scale dissolution agent. The strong Fe-S bonds in the pyrite (FeS2) scale are broken and the sulfur reacts with the potassium ions of borax. This gives rise to free Fe2+ ions which can now be removed with chelating agents. The chelating agents can capture or bind to these free Fe2+ ions and aid in their removal. Hence, the binding affinities, ecotoxicological properties of these novel chemicals, are studied. Moreover, the calculation of the binding affinities of chelating agents to a central metal ion such as Fe2+ using DFT has been found to correlate with their corresponding experimental stability constant [11, 29]. The electronic-structure properties, such as the electrostatic potential map and frontier molecular orbitals of the most promising chemical, are calculated and overall activity is compared to DTPA, which is a well-known iron sulfide scale remover.


## 2. Methodology

### 2.1. Designing of Chemicals

The novel chemicals were designed after macrocycles, which have been used as iron chelators [30, 31] and DTPA which has been previously studied by our group in previous works as an effective iron sulfide scale remover [2, 10–12, 32]. Table 1 shows the IUPAC name and the corresponding acronym of the designed novel chemicals. TTCC and TCTN are 12-membered ring macrocycles while CMAT and BOEN were designed based on the triamine scaffold in DTPA. Figure 1 shows a flow chart depicting the road map of the novel chemicals used in this study. The structures (Figure 2) of the designed chemicals show that TCTN and CMAT have carboxylic function groups while TTCC and BOEN are hydroxamates. PubChem database was used to confirm that the chemicals are novel [33]. It is crucial to note that though Fe2+ is a borderline lewis acid, borderline donor groups such as those containing amino groups or aromatic rings with nitrogen atoms such as pyridine are recommended as the right ligands to form complexes with it [34]. Many borderline donor groups have already been studied with Fe2+ [35–37]; hence to ensure the novelty of these chemicals, other groups such as hard bases were explored. Moreover, the combination of hard and borderline donor atoms was considered in the designing of these novel chemicals; this is evident in the structures of TCTN and CMAT (Figure 2). This design was done in order to deduce theoretically which donor groups are preferred for binding between hard and borderline bases.Table 1
IUPAC names of designed novel chemicals.
IUPAC nameAcronymN1,N4,N7,N10-Tetrahydroxy-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracarboxamideTTCC6,6′,6″,6‴-((1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(ethane-2,1-diyl))tetranicotinic acidTCTN6,6′,6″,6‴-((((((5-Carboxypyridin-2-yl)methyl)azanediyl)bis(ethane-2,1-diyl))bis(azanetriyl))tetrakis(methylene))tetranicotinic acidCMAT2,2'-((3-(1-(2-(bis(2-(Hydroxyamino)-2-oxoethyl)amino)ethyl)-3-hydroxyureido)propyl)azanediyl)bis(N-hydroxyacetamide)BOENFigure 1
Flow chart depicting novel designing of novel chemicals for iron sulfide scale inhibition.Figure 2
Novel chelating agents: (a) TTCC, (b) TCTN, (c) CMAT, and (d) BOEN studied for iron sulfide scale removal.
(a)(b)(c)(d)


### 2.2. Computational Details

Gaussian 09 [38] was employed for all DFT calculations at the B3LYP/def2TZVP basis set using the polarizable continuum model (PCM) for the solvation [39]. This methodology has been used in our earlier computational studies on iron sulfide scale removal [10, 11, 32]. The vibrational frequencies were also calculated, and it was ensured there was absence of imaginary frequencies which implied that the optimized structures had reached a true minimum. The binding energies between the designed chemicals and the metal iron were calculated using equation (1) from the values of their respective sum of electronic and thermal free energies (Ɛ0 + Gcorr) [40]. The ecotoxicity properties of the designed chemicals were predicted using the ADMETopt web tool [41]. Gauss View version 5.0 [42] and Avogadro version 1.1.1 [43] were used as visualization tools for the optimized structures:(1)BE=EFe−complex−Ecompound−EFe.


## 2.1. Designing of Chemicals

The novel chemicals were designed after macrocycles, which have been used as iron chelators [30, 31] and DTPA which has been previously studied by our group in previous works as an effective iron sulfide scale remover [2, 10–12, 32]. Table 1 shows the IUPAC name and the corresponding acronym of the designed novel chemicals. TTCC and TCTN are 12-membered ring macrocycles while CMAT and BOEN were designed based on the triamine scaffold in DTPA. Figure 1 shows a flow chart depicting the road map of the novel chemicals used in this study. The structures (Figure 2) of the designed chemicals show that TCTN and CMAT have carboxylic function groups while TTCC and BOEN are hydroxamates. PubChem database was used to confirm that the chemicals are novel [33]. It is crucial to note that though Fe2+ is a borderline lewis acid, borderline donor groups such as those containing amino groups or aromatic rings with nitrogen atoms such as pyridine are recommended as the right ligands to form complexes with it [34]. Many borderline donor groups have already been studied with Fe2+ [35–37]; hence to ensure the novelty of these chemicals, other groups such as hard bases were explored. Moreover, the combination of hard and borderline donor atoms was considered in the designing of these novel chemicals; this is evident in the structures of TCTN and CMAT (Figure 2). This design was done in order to deduce theoretically which donor groups are preferred for binding between hard and borderline bases.Table 1
IUPAC names of designed novel chemicals.
IUPAC nameAcronymN1,N4,N7,N10-Tetrahydroxy-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracarboxamideTTCC6,6′,6″,6‴-((1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrayl)tetrakis(ethane-2,1-diyl))tetranicotinic acidTCTN6,6′,6″,6‴-((((((5-Carboxypyridin-2-yl)methyl)azanediyl)bis(ethane-2,1-diyl))bis(azanetriyl))tetrakis(methylene))tetranicotinic acidCMAT2,2'-((3-(1-(2-(bis(2-(Hydroxyamino)-2-oxoethyl)amino)ethyl)-3-hydroxyureido)propyl)azanediyl)bis(N-hydroxyacetamide)BOENFigure 1
Flow chart depicting novel designing of novel chemicals for iron sulfide scale inhibition.Figure 2
Novel chelating agents: (a) TTCC, (b) TCTN, (c) CMAT, and (d) BOEN studied for iron sulfide scale removal.
(a)(b)(c)(d)


## 2.2. Computational Details

Gaussian 09 [38] was employed for all DFT calculations at the B3LYP/def2TZVP basis set using the polarizable continuum model (PCM) for the solvation [39]. This methodology has been used in our earlier computational studies on iron sulfide scale removal [10, 11, 32]. The vibrational frequencies were also calculated, and it was ensured there was absence of imaginary frequencies which implied that the optimized structures had reached a true minimum. The binding energies between the designed chemicals and the metal iron were calculated using equation (1) from the values of their respective sum of electronic and thermal free energies (Ɛ0 + Gcorr) [40]. The ecotoxicity properties of the designed chemicals were predicted using the ADMETopt web tool [41]. Gauss View version 5.0 [42] and Avogadro version 1.1.1 [43] were used as visualization tools for the optimized structures:(1)BE=EFe−complex−Ecompound−EFe.


## 3. Results and Discussion

### 3.1. Binding Affinities of Novel Chemicals

DFT calculation was used to calculate the binding affinity between the designed chemicals and Fe2+ using equation (1). All the chemicals formed coordinated bonds with the central metal ion. TTCC formed a perfect square pyramidal shape while TCTN and CMAT had a trigonal bipyramidal shape and BOEN and a near-octahedral shape forming six coordinated bonds with the central metal ion (Figure 3). However, all the binding energies were highly positive particularly TCTN and CMAT except for BOEN which had a negative value of −3.354 kcal/mol for its binding energy (Table 2). The values of the binding energies are synonymous with the free energies of the reaction of the complexes studied. The free energies are calculated using the values from the thermal correction to Gibbs free energy from the Gaussian 09 program [38, 40]. This implied that the presence of the aromatic groups reduced the binding capacity of the chemicals as can be seen in Fe-TCTN and Fe-CMAT. This may be due to steric hindrance. However, this very high positive energy is not observed in Fe-TTCC and it is absent in Fe-BOEN, which is the only one that has a good binding affinity among the studied chemicals.Figure 3
Complexes of the studied chemicals with Fe2+. (a) Fe-TTCC. (b) Fe-TCTN. (c) Fe-CMAT. (d) Fe-BOEN.
(a)(b)(c)(d)Table 2
Calculated binding energies (BE) of the studied novel chemicals.
Complex (kcal/mol)Ligand (kcal/mol)Fe2+ (kcal/mol)BE (kcal/mol)GeometryFe-TTCC−1433116.967TTCC−641000.933−792898.568782.533Square pyramidalFe-TCTN−2320366.446TCTN−1626139.180−792898.56898671.302Trigonal bipyramidalFe-CMAT−2482126.589CMAT−1692691.646−792898.5683463.625Trigonal bipyramidalFe-BOEN−1760370.949BOEN−967469.027−792898.568−3.354Near-octahedral


### 3.2. Ecotoxicity Prediction of Novel Chemicals

Besides the screening of the studied chemicals using their binding affinities to the central metal ion, Fe2+ their ecological toxicity (ecotox) properties were also predicted. This was done to determine how environmentally friendly these chemicals might be. ADMETSAR 2.0 [41, 44] web tool which uses machine learning techniques was used for the ecotox prediction as depicted in Table 3. The SMILES (simplified molecular-input line-entry system) of the studied chemicals was used as the input parameter. The results of only the toxicity properties (ecotox) were considered as other properties such as absorption, distribution, and metabolism (ADME) are irrelevant in this work since its application is not in drug discovery. All the chemicals were safe with respect to carcinogenicity, eye irritation, honey-bee and crustacean toxicity, and biodegradation. However, they were all slightly toxic concerning their acute oral toxicity as they fall into the category of the third class. Chemicals in class IV are nontoxic while those in classes II and I are toxic with class I being the most toxic [45, 46]. Only TTCC was found to be mutagenic as it had a 54% chance of being AMES toxic. TCTN and CMAR were found to be slightly toxic concerning fish toxicity, and this could pose a problem especially if these chemicals were used in offshore production operations. Besides the acute oral toxicity, BOEN has good ecotox properties. Moreover, the category of acute oral toxicity of BOEN is not relevant as these chemicals will not be consumed orally.Table 3
Predicted ecotoxicity of the studied novel chemicals.
CategoryTTCCTCTNCMATBOENProbability (remark)Probability (remark)Probability (remark)Probability (remark)Carcinogenicity(Safe) 0.46(Safe) 0.66(Safe) 0.66(Safe) 0.46Eye irritation(Safe) 0.70(Safe) 0.87(Safe) 0.89(Safe) 0.76Ames mutagenesis(Danger) 0.54(Safe) 0.74(Safe) 0.61(Safe) 0.64Acute oral toxicity (class III)(Caution) 0.57(Caution) 0.67(Caution) 0.64(Caution) 0.57Honey bee toxicity(Safe) 0.70(Safe) 0.80(Safe) 0.84(Safe) 0.68Biodegradation(Safe)0.63(Safe) 0.68(Safe) 0.83(Safe) 0.65Crustacean aquatic toxicity(Safe) 0.85(Safe) 0.87(Safe) 0.6(Safe) 0.71Fish aquatic toxicity(Safe) 0.76(Slightly toxic) 0.77(Slightly toxic) 0.40(Safe) 0.81Water solubility (logS)(Insoluble) 2.28(Soluble) −3.03(Soluble) −2.71(Soluble) −2.26


### 3.3. Electronic Structure of the Selected Chemical

The electronic-structure properties which include the electrostatic potential (ESP) and the frontier molecular orbitals maps were calculated for BOEN. The ESP map (Figure4) denotes the charge distribution highlighting both the electronegative and electropositive regions of the molecule. The ESP decreases in the order of blue, green, yellow, orange, and red where blue denotes the region with the highest electropositivity while red denotes the region with the highest electronegativity [47]. The red region mainly occurs around the hydroxamate moieties especially on the left part of the molecule where three hydroxamate moieties are in close proximity as compared to the other two hydroxamate moieties on the right whose region is between yellow and orange. The overall ESP of the molecule denotes that it is electronegative and this is expected as it will be attracted to a positively charged Fe2+ ion. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) make up the frontier molecular orbitals (Figures 4(b) and 4(c)) and denote the delocalization of electrons. The HOMO shows the electrons are delocalized all through the molecule except for one hydroxamate moiety on the right. Most of the delocalization occurs at the central hydroxamate moiety. The reverse is observed in the LUMO, where the delocalization can be seen dominant on the hydroxamate moiety on the right and practically absent on the central hydroxamate moiety. These differences may be due to the effect of the –CH2– groups that occur on both sides of the central hydroxamate moiety while only once in the hydroxamate moiety on the right.Figure 4
The (a) ESP, (b) HOMO, and (c) LUMO maps of BOEN.
(a)(b)(c)


### 3.4. Optimization of the Selected Chemical

The binding energy of BOEN with one Fe2+ is −3.354 kcal/mol. However, it was observed that one hydroxamate group was not involved in bonding with the central metal ion (Figure 5(a)). Hence, BOEN was optimized by adding another Fe2+ ion to make it two metal ions bound to BOEN. BOEN was complexed with another Fe2+ ion to see if the free hydroxamates group not participating in forming coordinated bonds with the central Fe2+ ion would be involved in complexation. However, the absence of water molecules hindered the stability of the complex formed. The addition of explicit water molecules is known to improve the stability of complexes [48]. Fe2+ is known to form hexaaquairon that is Fe2+(H2O)6 with a binding energy of −32.5 kcal/mol [49, 50]. However, when complexed with BOEN, the addition of up to 5 explicit water molecules creates a stable square pyramidal shape with each Fe2+ at the central metal ion as depicted in Figures 6(b) and 7(d). Hence, the choice of using five explicit water molecules as larger numbers of water molecules made the complex unstable. Upon the addition of another Fe2+ ion to make it three ions to complex with BOEN, the structure became destabilized. The stability of BOEN with just two Fe2+ ions can be seen that, unlike when complexed with one Fe2+ ion where the chelation is compacted, BOEN stretches and binds with the two central Metal ions at two ends. The addition of another Fe2+ destabilizes this geometry.Figure 5
BOEN binding with (a) one and (b) two Fe ions.
(a)(b)Figure 6
BOEN complexed with (a) one Fe2+ and (b) two Fe2+ ions showing the intrahydrogen bonding in broken yellow lines.
(a)(b)Figure 7
The optimized structures of DTPA complexed with (a) one and (c) two Fe2+ ions and the optimized structure of BOEN complexed, (b) one (d) two Fe2+ ions.
(a)(b)(c)(d)This new complex was optimized (Figure5(b)) and the geometrical parameters of both the optimized structure of BOEN binding to one and two Fe2+ central metal ions were studied (Tables 4 and 5). The binding energy of BOEN to two Fe2+ ions increased from −3.354 to −340.947 kcal/mol. However, 5 explicit water molecules were included when BOEN was complexed to two Fe2+ ions. These water molecules increased the binding affinity of BOEN with Fe2+ by enabling the formation of a near square pyramidal complex (Figure 5(b)) with each Fe2+ ion forming five coordinated bonds each. The binding energy upon optimization of BOEN was calculated using equation (2). The average Fe-O bond length in the BOEN complex with one Fe2+ ion was longer (2.035 Å) than in BOEN with two Fe2+ ions (2.015 Å) as deduced from Tables 4 and 5. However, there were no Fe-N bonds in BOEN complexed with two Fe2+ ions as they were either bonded to the oxygen of the hydroxamate moiety or the oxygen from the water molecule. The shorter bond length in the latter corroborates the reason why higher binding energy is observed when BOEN binds to two Fe2+ ions. A larger bond angle correlates with a smaller bond length and vice versa and this is observed here.Table 4
The bond parameters of BOEN bonded to one Fe2+ ion.
BondDist. (Å)<O-Fe-O angleDegrees (°)Fe41-O12.008O1-Fe41-O1689.0Fe41-N52.118O1-Fe41-O23100.1Fe41-O122.051N5-Fe41-O16110.3Fe41-O162.029N19-Fe41-O2377.9Fe41-N192.192N5-Fe41-O1285.9Fe41-O232.053O12-Fe41-N1989.5Table 5
The bond parameters of BOEN bonded with two Fe2+ ions.
BondDist.(Å)<OMO angleDegrees (°)Fe42-O11.965O46-Fe41-O4389.6Fe42-O121.936O27-Fe41-O4683.7Fe42-O161.936O23-Fe41-O2799.7Fe41-O231.959O46-Fe41-O5696.6Fe41-O271.930O1-Fe42-O4978.8Fe41-O432.013O12-Fe42-O1688.8Fe41-O462.067O49-Fe42-O5293.3Fe41-O562.080O16-Fe42-O5293.3Fe42-O492.122O12-Fe42-O4986.8Fe42-O522.141O1-Fe42-O16104.9To further understand why BOEN had good binding energy to Fe2+ ion compared to the other studied chemicals, the presence of hydrogen bonding was investigated. It has been reported that hydrogen bonding contributes about 1.5 kcal/mol to binding energy [45, 51]. BOEN showed the presence of intramolecular hydrogen bonding when complexed with both one Fe2+ and two Fe2+ ions (Figure 6). The hydrogen bond occurred between the hydrogen atom in one hydroxamate moiety and another oxygen atom in another hydroxamate moiety whereas, in BOEN complexed with two Fe2+ ions, the hydrogen bonding occurs between the oxygen atom of the hydroxamate moiety and the hydrogen atom of the water molecules (Figure 6(b)):(2)BE=EFe−complex−Ecompound−EFe−E5H2O.


### 3.5. Comparison of the Selected Chemical with DTPA

BOEN was compared with DTPA which served as the reference standard. DTPA has been previously studied as an effective iron sulfide scale removal [8, 12]. The binding energy of DTPA with Fe2+ ion was calculated as −57.128 kcal/mol [11] which is higher when compared to BOEN complexed with a single Fe2+ ion (−3.354 kcal/mol). However, when the binding energy of DTPA complexed with two Fe2+ ions was calculated and compared with BOEN (Figure 7), the former has a binding energy of −295.193 kcal/mol while BOEN had binding energy of −340.947 kcal/mol (Table 6). Upon complexation with two Fe2+ ions and five water molecules, BOEN surpassed DTPA in binding energy. The difference in binding energies is due to the different geometry which both DTPA and BOEN undergo upon binding with two Fe2+ ions and the presence of five water molecules in BOEN. These explicit water molecules used in BOEN are not required in DTPA to form a stable complex with good geometry. The ecotoxicity properties of both BOEN and DTPA were also compared (Table 7). BOEN had better ecotoxicological properties concerning carcinogenicity and eye irritation as it was safer than DTPA. The eye irritation predicted for DTPA correlates with what has been reported by the European Chemical Agency which described DTPA as a chemical that causes serious eye irritation [52]. A reaction scheme (Figure 8) proposed how BOEN could be synthesized using DTPA as the starting material. This would hopefully help experimental chemists in synthesizing this new chemical.Table 6
Calculated binding energies (BE) of the DTPA and BOEN complexes.
Complex (kcal/mol)Ligand (kcal/mol)Fe2+ (kcal/mol)5H2O (kcal/mol)BE (kcal/mol)Fe-DTPA−1710267.251DTPA−917311.555−792898.568−239901.357−57.1282Fe-DTPA−2503038.816−1585432.068∗−239901.357−295.193Fe-BOEN−1760370.949BOEN−967469.027−792898.568−239901.357−3.3542Fe-BOEN.5H2O∗−2793143.399−1585432.068∗−239901.357−340.947∗2 Fe2+ ions; energy of 5 H2O = −239901.357.Table 7
Predicted ecotoxicity of the selected chemical and DTPA.
CategoryBOENDTPAProbability (remark)Probability (remark)Carcinogenicity(Safe) 0.46(Safe) 0.65Eye irritation(Safe) 0.76(Irritant) 0.95Ames mutagenesis(Safe) 0.64(Safe) 0.96Acute oral toxicity (class III)(Caution) 0.57(Caution) 0.81Honey bee toxicity(Safe) 0.68(Safe) 0.62Biodegradation(Safe) 0.65(Safe) 0.50Crustacean aquatic toxicity(Safe) 0.71(Safe) 0.93Fish aquatic toxicity(Safe) 0.81(Safe) 0.79Water solubility (logS)(Soluble) −2.26(Soluble) −1.24Figure 8
Proposed reaction scheme of BOEN synthesis from DTPA.


## 3.1. Binding Affinities of Novel Chemicals

DFT calculation was used to calculate the binding affinity between the designed chemicals and Fe2+ using equation (1). All the chemicals formed coordinated bonds with the central metal ion. TTCC formed a perfect square pyramidal shape while TCTN and CMAT had a trigonal bipyramidal shape and BOEN and a near-octahedral shape forming six coordinated bonds with the central metal ion (Figure 3). However, all the binding energies were highly positive particularly TCTN and CMAT except for BOEN which had a negative value of −3.354 kcal/mol for its binding energy (Table 2). The values of the binding energies are synonymous with the free energies of the reaction of the complexes studied. The free energies are calculated using the values from the thermal correction to Gibbs free energy from the Gaussian 09 program [38, 40]. This implied that the presence of the aromatic groups reduced the binding capacity of the chemicals as can be seen in Fe-TCTN and Fe-CMAT. This may be due to steric hindrance. However, this very high positive energy is not observed in Fe-TTCC and it is absent in Fe-BOEN, which is the only one that has a good binding affinity among the studied chemicals.Figure 3
Complexes of the studied chemicals with Fe2+. (a) Fe-TTCC. (b) Fe-TCTN. (c) Fe-CMAT. (d) Fe-BOEN.
(a)(b)(c)(d)Table 2
Calculated binding energies (BE) of the studied novel chemicals.
Complex (kcal/mol)Ligand (kcal/mol)Fe2+ (kcal/mol)BE (kcal/mol)GeometryFe-TTCC−1433116.967TTCC−641000.933−792898.568782.533Square pyramidalFe-TCTN−2320366.446TCTN−1626139.180−792898.56898671.302Trigonal bipyramidalFe-CMAT−2482126.589CMAT−1692691.646−792898.5683463.625Trigonal bipyramidalFe-BOEN−1760370.949BOEN−967469.027−792898.568−3.354Near-octahedral


## 3.2. Ecotoxicity Prediction of Novel Chemicals

Besides the screening of the studied chemicals using their binding affinities to the central metal ion, Fe2+ their ecological toxicity (ecotox) properties were also predicted. This was done to determine how environmentally friendly these chemicals might be. ADMETSAR 2.0 [41, 44] web tool which uses machine learning techniques was used for the ecotox prediction as depicted in Table 3. The SMILES (simplified molecular-input line-entry system) of the studied chemicals was used as the input parameter. The results of only the toxicity properties (ecotox) were considered as other properties such as absorption, distribution, and metabolism (ADME) are irrelevant in this work since its application is not in drug discovery. All the chemicals were safe with respect to carcinogenicity, eye irritation, honey-bee and crustacean toxicity, and biodegradation. However, they were all slightly toxic concerning their acute oral toxicity as they fall into the category of the third class. Chemicals in class IV are nontoxic while those in classes II and I are toxic with class I being the most toxic [45, 46]. Only TTCC was found to be mutagenic as it had a 54% chance of being AMES toxic. TCTN and CMAR were found to be slightly toxic concerning fish toxicity, and this could pose a problem especially if these chemicals were used in offshore production operations. Besides the acute oral toxicity, BOEN has good ecotox properties. Moreover, the category of acute oral toxicity of BOEN is not relevant as these chemicals will not be consumed orally.Table 3
Predicted ecotoxicity of the studied novel chemicals.
CategoryTTCCTCTNCMATBOENProbability (remark)Probability (remark)Probability (remark)Probability (remark)Carcinogenicity(Safe) 0.46(Safe) 0.66(Safe) 0.66(Safe) 0.46Eye irritation(Safe) 0.70(Safe) 0.87(Safe) 0.89(Safe) 0.76Ames mutagenesis(Danger) 0.54(Safe) 0.74(Safe) 0.61(Safe) 0.64Acute oral toxicity (class III)(Caution) 0.57(Caution) 0.67(Caution) 0.64(Caution) 0.57Honey bee toxicity(Safe) 0.70(Safe) 0.80(Safe) 0.84(Safe) 0.68Biodegradation(Safe)0.63(Safe) 0.68(Safe) 0.83(Safe) 0.65Crustacean aquatic toxicity(Safe) 0.85(Safe) 0.87(Safe) 0.6(Safe) 0.71Fish aquatic toxicity(Safe) 0.76(Slightly toxic) 0.77(Slightly toxic) 0.40(Safe) 0.81Water solubility (logS)(Insoluble) 2.28(Soluble) −3.03(Soluble) −2.71(Soluble) −2.26


## 3.3. Electronic Structure of the Selected Chemical

The electronic-structure properties which include the electrostatic potential (ESP) and the frontier molecular orbitals maps were calculated for BOEN. The ESP map (Figure4) denotes the charge distribution highlighting both the electronegative and electropositive regions of the molecule. The ESP decreases in the order of blue, green, yellow, orange, and red where blue denotes the region with the highest electropositivity while red denotes the region with the highest electronegativity [47]. The red region mainly occurs around the hydroxamate moieties especially on the left part of the molecule where three hydroxamate moieties are in close proximity as compared to the other two hydroxamate moieties on the right whose region is between yellow and orange. The overall ESP of the molecule denotes that it is electronegative and this is expected as it will be attracted to a positively charged Fe2+ ion. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) make up the frontier molecular orbitals (Figures 4(b) and 4(c)) and denote the delocalization of electrons. The HOMO shows the electrons are delocalized all through the molecule except for one hydroxamate moiety on the right. Most of the delocalization occurs at the central hydroxamate moiety. The reverse is observed in the LUMO, where the delocalization can be seen dominant on the hydroxamate moiety on the right and practically absent on the central hydroxamate moiety. These differences may be due to the effect of the –CH2– groups that occur on both sides of the central hydroxamate moiety while only once in the hydroxamate moiety on the right.Figure 4
The (a) ESP, (b) HOMO, and (c) LUMO maps of BOEN.
(a)(b)(c)


## 3.4. Optimization of the Selected Chemical

The binding energy of BOEN with one Fe2+ is −3.354 kcal/mol. However, it was observed that one hydroxamate group was not involved in bonding with the central metal ion (Figure 5(a)). Hence, BOEN was optimized by adding another Fe2+ ion to make it two metal ions bound to BOEN. BOEN was complexed with another Fe2+ ion to see if the free hydroxamates group not participating in forming coordinated bonds with the central Fe2+ ion would be involved in complexation. However, the absence of water molecules hindered the stability of the complex formed. The addition of explicit water molecules is known to improve the stability of complexes [48]. Fe2+ is known to form hexaaquairon that is Fe2+(H2O)6 with a binding energy of −32.5 kcal/mol [49, 50]. However, when complexed with BOEN, the addition of up to 5 explicit water molecules creates a stable square pyramidal shape with each Fe2+ at the central metal ion as depicted in Figures 6(b) and 7(d). Hence, the choice of using five explicit water molecules as larger numbers of water molecules made the complex unstable. Upon the addition of another Fe2+ ion to make it three ions to complex with BOEN, the structure became destabilized. The stability of BOEN with just two Fe2+ ions can be seen that, unlike when complexed with one Fe2+ ion where the chelation is compacted, BOEN stretches and binds with the two central Metal ions at two ends. The addition of another Fe2+ destabilizes this geometry.Figure 5
BOEN binding with (a) one and (b) two Fe ions.
(a)(b)Figure 6
BOEN complexed with (a) one Fe2+ and (b) two Fe2+ ions showing the intrahydrogen bonding in broken yellow lines.
(a)(b)Figure 7
The optimized structures of DTPA complexed with (a) one and (c) two Fe2+ ions and the optimized structure of BOEN complexed, (b) one (d) two Fe2+ ions.
(a)(b)(c)(d)This new complex was optimized (Figure5(b)) and the geometrical parameters of both the optimized structure of BOEN binding to one and two Fe2+ central metal ions were studied (Tables 4 and 5). The binding energy of BOEN to two Fe2+ ions increased from −3.354 to −340.947 kcal/mol. However, 5 explicit water molecules were included when BOEN was complexed to two Fe2+ ions. These water molecules increased the binding affinity of BOEN with Fe2+ by enabling the formation of a near square pyramidal complex (Figure 5(b)) with each Fe2+ ion forming five coordinated bonds each. The binding energy upon optimization of BOEN was calculated using equation (2). The average Fe-O bond length in the BOEN complex with one Fe2+ ion was longer (2.035 Å) than in BOEN with two Fe2+ ions (2.015 Å) as deduced from Tables 4 and 5. However, there were no Fe-N bonds in BOEN complexed with two Fe2+ ions as they were either bonded to the oxygen of the hydroxamate moiety or the oxygen from the water molecule. The shorter bond length in the latter corroborates the reason why higher binding energy is observed when BOEN binds to two Fe2+ ions. A larger bond angle correlates with a smaller bond length and vice versa and this is observed here.Table 4
The bond parameters of BOEN bonded to one Fe2+ ion.
BondDist. (Å)<O-Fe-O angleDegrees (°)Fe41-O12.008O1-Fe41-O1689.0Fe41-N52.118O1-Fe41-O23100.1Fe41-O122.051N5-Fe41-O16110.3Fe41-O162.029N19-Fe41-O2377.9Fe41-N192.192N5-Fe41-O1285.9Fe41-O232.053O12-Fe41-N1989.5Table 5
The bond parameters of BOEN bonded with two Fe2+ ions.
BondDist.(Å)<OMO angleDegrees (°)Fe42-O11.965O46-Fe41-O4389.6Fe42-O121.936O27-Fe41-O4683.7Fe42-O161.936O23-Fe41-O2799.7Fe41-O231.959O46-Fe41-O5696.6Fe41-O271.930O1-Fe42-O4978.8Fe41-O432.013O12-Fe42-O1688.8Fe41-O462.067O49-Fe42-O5293.3Fe41-O562.080O16-Fe42-O5293.3Fe42-O492.122O12-Fe42-O4986.8Fe42-O522.141O1-Fe42-O16104.9To further understand why BOEN had good binding energy to Fe2+ ion compared to the other studied chemicals, the presence of hydrogen bonding was investigated. It has been reported that hydrogen bonding contributes about 1.5 kcal/mol to binding energy [45, 51]. BOEN showed the presence of intramolecular hydrogen bonding when complexed with both one Fe2+ and two Fe2+ ions (Figure 6). The hydrogen bond occurred between the hydrogen atom in one hydroxamate moiety and another oxygen atom in another hydroxamate moiety whereas, in BOEN complexed with two Fe2+ ions, the hydrogen bonding occurs between the oxygen atom of the hydroxamate moiety and the hydrogen atom of the water molecules (Figure 6(b)):(2)BE=EFe−complex−Ecompound−EFe−E5H2O.


## 3.5. Comparison of the Selected Chemical with DTPA

BOEN was compared with DTPA which served as the reference standard. DTPA has been previously studied as an effective iron sulfide scale removal [8, 12]. The binding energy of DTPA with Fe2+ ion was calculated as −57.128 kcal/mol [11] which is higher when compared to BOEN complexed with a single Fe2+ ion (−3.354 kcal/mol). However, when the binding energy of DTPA complexed with two Fe2+ ions was calculated and compared with BOEN (Figure 7), the former has a binding energy of −295.193 kcal/mol while BOEN had binding energy of −340.947 kcal/mol (Table 6). Upon complexation with two Fe2+ ions and five water molecules, BOEN surpassed DTPA in binding energy. The difference in binding energies is due to the different geometry which both DTPA and BOEN undergo upon binding with two Fe2+ ions and the presence of five water molecules in BOEN. These explicit water molecules used in BOEN are not required in DTPA to form a stable complex with good geometry. The ecotoxicity properties of both BOEN and DTPA were also compared (Table 7). BOEN had better ecotoxicological properties concerning carcinogenicity and eye irritation as it was safer than DTPA. The eye irritation predicted for DTPA correlates with what has been reported by the European Chemical Agency which described DTPA as a chemical that causes serious eye irritation [52]. A reaction scheme (Figure 8) proposed how BOEN could be synthesized using DTPA as the starting material. This would hopefully help experimental chemists in synthesizing this new chemical.Table 6
Calculated binding energies (BE) of the DTPA and BOEN complexes.
Complex (kcal/mol)Ligand (kcal/mol)Fe2+ (kcal/mol)5H2O (kcal/mol)BE (kcal/mol)Fe-DTPA−1710267.251DTPA−917311.555−792898.568−239901.357−57.1282Fe-DTPA−2503038.816−1585432.068∗−239901.357−295.193Fe-BOEN−1760370.949BOEN−967469.027−792898.568−239901.357−3.3542Fe-BOEN.5H2O∗−2793143.399−1585432.068∗−239901.357−340.947∗2 Fe2+ ions; energy of 5 H2O = −239901.357.Table 7
Predicted ecotoxicity of the selected chemical and DTPA.
CategoryBOENDTPAProbability (remark)Probability (remark)Carcinogenicity(Safe) 0.46(Safe) 0.65Eye irritation(Safe) 0.76(Irritant) 0.95Ames mutagenesis(Safe) 0.64(Safe) 0.96Acute oral toxicity (class III)(Caution) 0.57(Caution) 0.81Honey bee toxicity(Safe) 0.68(Safe) 0.62Biodegradation(Safe) 0.65(Safe) 0.50Crustacean aquatic toxicity(Safe) 0.71(Safe) 0.93Fish aquatic toxicity(Safe) 0.81(Safe) 0.79Water solubility (logS)(Soluble) −2.26(Soluble) −1.24Figure 8
Proposed reaction scheme of BOEN synthesis from DTPA.


## 4. Conclusion

Iron sulfide scale removal has been a significant challenge in the oil and gas industry during production. Developing effective and green chemicals capable of removing this scale has become pertinent. Herein, four novel chemicals, TTCC, TCTN, CMAT, and BOEN, are designed usingin silico method. Their binding energies were 795.56, 98637.83, 3436.95, and −3.354 kcal/mol, respectively. All the designed chemicals had poor binding affinities with Fe2+ ion except for BOEN which was the only one which had negative binding energy and hence good binding affinity. The ecological toxicity properties were predicted for the four chemicals of which only BOEN proved to be the safest. The others were predicted to have fish toxicity or were mutagenic. Upon optimization of BOEN by binding it to two Fe2+ ions and adding five explicit water molecules, its binding affinity increased to −340.947 kcal/mol which is higher when DTPA is complexed with two Fe2+ ions. The ecotoxicological properties of both DTPA and BOEN were also compared with the latter safer to use than the former. Hence, in both binding affinity and toxicity, BOEN is predicted to be a better choice than DTPA. It was observed that the presence of hydrogen bonding between the hydroxamate moieties and water molecules contributed to the good binding affinity of BOEN. It is important to note that the binding energy of one molecule of DTPA to Fe2+ (−57.128 kcal/mol) is greater than single BOEN to Fe2+ (−3.354 kcal/mol). However upon complexation with two Fe2+ ions, BOEN (−340.947) has a higher binding energy than DTPA (−295.193 kcal/mol). The reasons for this are the orientation of the BOEN molecule when complexing with two Fe2+ ions and the explicit water molecules present whilst complexing with two Fe2+ ions which are not present when DTPA complexes with two Fe2+ ions. Nevertheless, this work is to provide insight and guide experimental scientist in synthesizing novel green chemicals that can be used for iron sulfide scale removal.



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