Adsorption characteristics of sulfonamide antibiotic molecules on carbon nanotube and the effects of environment

In this paper, the adsorption characteristics of five sulfonamide antibiotic molecules on carbon nanotubes were investigated using density functional theory (DFT) calculations. The adsorption configurations of different adsorption sites were optimized, and the most stable adsorption configuration of each sulfonamide molecule was determined by adsorption energy comparison, and the relative adsorption stability of five sulfonamide molecules on carbon nanotubes was determined by comparing their adsorption energies, i.e., sulfamethazine > sulfadiazine > sulfamerazine > sulfamethoxazole > sulfanilamide. The electron densities of the adsorption configurations were then calculated to confirm that the adsorption of five sulfonamide drug molecules on carbon nanotubes should be physical adsorption. Moreover, the adsorption energy of five sulfonamide molecules on carbon nanotubes in the aqueous environment was larger than that in the vacuum even though the adsorption process remain to be physical adsorption. The adsorption characteristics of the five sulfonamide molecules in various acid–base environments were finally investigated. In contrast, the adsorption energies of the five drug molecules in acid–base environments were significantly reduced, indicating that carbon nanotubes may need to have a suitable pH range to achieve the optimal adsorption effect when they are used for the treatment of sulfonamide antibiotics. In this paper, we use density functional theory (DFT) with PBE functional to study the adsorption properties of five sulfonamides on carbon nanotubes. The structural optimization and the calculation of electronic structural properties are carried out by CP2K package (version 7.1), adopting the DZVP-MOLOPT-SR-GTH basis set and Goedeck-Teter-Hutter (GTH) pseudo potential. Grimme’s D3 correction is used to during all the calculations to correctly capture the influence of the van der Waals interactions.


Introduction
In recent years, the increasing demand for sulfonamide antibiotics, which are mainly used in clinical treatment, has resulted in serious environmental problems. These unabsorbed drugs will be excreted in the form of human urine or feces, and a large number of residual antibiotic drugs will eventually enter the environment, leading to a novel type of pollution [1,2]. Overuse of antibiotic drugs is harmful to the growth of organisms [3]. Specifically, sulfonamide antibiotics will damage the growth of algae, and high concentration of sulfonamide antibiotics will inhibit the metabolism of folate in algae [4]. To reduce the pollution of sulfonamide antibiotics, current common treatment methods include the following: (1) biological method: the use of microorganisms for metabolic degradation of pollution sources, (2) chemical treatment: using chemical reagents to react with pollution sources to achieve the purpose of removal, and (3) adsorption method: principally with the help of adsorbent for pollutant enrichment treatment. Unlike other methods, the adsorption method is environmentally friendly because it does not produce any chemical reactions or secondary pollution during the whole treatment process. As a result, it is widely used in environmental treatment now [5].
The key to utilizing this method is to use the right adsorbents, and some common traditional adsorbents include activated 1 3 150 Page 2 of 9 carbon, graphene, and carbon nanotubes. However, different pH also has different effects on the adsorption of sulfonamides. Park et al. [6] studied that the decrease of pH value led to the increase of adsorption potential of antibiotics on soil materials with pH value of 4.0-8.0. This may be due to the large number of neutral and positively charged sulfonamides at low pH, which bind electrostatically to adsorption sites on the soil surface. Wang et al. [7] studied the adsorption of carbamazepine (CBZ) and sulfamethoxazole (SMX) on activated carbon (AC). Tang et al. [8] prepared a reduced graphene oxide/magnetite composite and studied the adsorption of ciprofloxacin and norfloxacin on the composite. The material can be used as an adsorbent to remove fluoroquinolones antibiotics. Tetracycline is also a common antibiotic drug, and it has been reported that Fe 3 O 4 -rGO composite can effectively remove tetracycline in the environment [9]. Gao et al. [10] studied the tetracycline adsorption mechanism of graphene oxide (GO). Carbon nanotubes have a unique hexagonal network spatial structure, which is highly uniform and the space generated will also increase the surface area and adsorption potential energy of carbon nanotubes, which is also the prerequisite for carbon nanotubes to be used as adsorbent [11,12]. Tian et al. [13] explored the influence of carbon nanotube-filled and unfilled columns on the outflow velocity of sulfamethoxazole (SMX) and sulfamepyridines (SPY) and discovered that there was an interaction between carbon nanotubes and SMX and SPY. This indicates that carbon nanotubes can be used as an adsorptive material to remove sulfonamide antibiotic molecules from water. Yuan et al. [14] prepared a magnetic nanocomposite multi-walled carbon nanotubes, which showed amazing adsorption capacity for sulfonamide antibiotic molecules. Zhang et al. [15] studied the adsorption effect of carbon nanotubes with different functions on sulfamethoxazole. Despite these great successes, the underlying mechanism for the adsorption of these compounds on carbon nanotubes and the possible influences of different environments remain largely unknown. In this paper, inspired by the experimental results of Liu et al. [16], the adsorption characteristics of sulfanilamide (SA), sulfamethoxazole (SMX), sulfadiazine (SDZ), sulfamethazine (SM2), and sulfamerazine (SM1) on carbon nanotubes were studied in detail. At the same time, the effects of carbon nanotubes on the adsorption of five sulfonamide antibiotics in the water environment, and acid-base environment were investigated. As a result, our work provides a theoretical basis for the use of carbon nanotubes as a kind of adsorbent for the treatment of antibiotics in the water environment.

Calculation methods
In this paper, density functional theory (DFT) with PBE [17,18] functional was adopted to study the adsorption characteristics of five sulfonamide antibiotic molecules on carbon nanotubes. The minimum energy structures studied in this work were first optimized using the D3 van der Waals (vdW). The D3 method is a dispersion correction strategy proposed by Grimme et al. [19]. The method can be coupled with most DFT functionals, and applies to all elements of the Periodic Table, ranging from to molecules and solids. Such a method improves accuracy for correcting predicting weak van der Waals interactions with nearly no increasing computational cost, which is important in cases where non-covalent intermolecular interactions are expected to play important roles. Interested readers can refer to relevant reference for more details [20,21]. The structural optimization and calculation of electronic structural properties were completed by CP2K package (version 7.1) [22] with DZVP-MOLOPT-SR-GTH [23] basis sets and Goedecker-Teter-Hutter (GTH) [24][25][26] pseudopotentials. Since there are numerous SWC-NTs available, it is hard to investigate all their properties. We chose SWCNT (6, 4) as a prototype since it is one of the most studied carbon nanotubes, and the synthesis methods are mature [27][28][29]. We chose (6, 4) single-walled carbon nanotubes, and the lattice parameters of the carbon nanotubes model are a = 25.00 Å, b = 25.00 Å, c = 18.57 Å, α = β = γ = 90°. Taking into account the structure of the five drug molecules, the vacuum layer was set at 15 Å to ensure that there was no interaction between adjacent carbon nanotubes and drug molecules. In neutral aqueous solution, under the universal force field and according to the density of 1 g/ cm 3 , H 2 O molecules are approximately added on the surfaces of CNT, respectively. In acidic (basic) conditions, H 2 O molecules were replaced by a molecule of HCl (NaOH). The distance between the HCl (NaOH) and the antibiotic molecule in the initial models was about 2.50-3.50 Å. The C-C bond length in the optimized stable carbon nanotube structure ranges from 1.382 to 1.453 Å, which is basically consistent with the previous work [30][31][32]. The adsorption energy of the system can be expressed as: . E SWCNT is the energy of carbon nanotubes. E M is the energy of a single sulfonamide drug, and E M+SWCNT is the energy of the system with sulfonamide molecules adsorbed on carbon nanotubes. Therefore, when E ads is negative, it represents an exothermic process. The larger the absolute value of E ads is, the stronger the adsorption between carbon nanotubes and sulfonamide drugs will be, and the more stable the adsorption system will be.
As shown in Fig. 1, three possible adsorption sites on carbon nanotubes were selected for adsorption, i.e., top site (1), bridge site (2), and hollow site (3). Additionally, possible adsorption sites of sulfonamides are the benzene ring (A), O atom of sulfonamide (B), and N atom on the amino group (C). Therefore, nine stable adsorption configurations were calculated for each sulfonamide molecule. A1, A2, and A3 represent the benzene ring of sulfonamide molecules adsorbed on the top, bridge, and hollow of carbon nanotubes respectively. B1, B2, and B3 represent the O atom of sulfonamide adsorbed on the top, bridge and hollow of carbon nanotubes. C1, C2, and C3 indicate that the N atom on the amino group of sulfonamides is adsorbed on the top, bridge, and hollow of carbon nanotubes. Based on these constructed structures, all possible adsorption configurations of five sulfonamides were optimized first, namely SA, SDZ, SM1, SM2, and SMX, on single-walled carbon nanotubes respectively.

Adsorption analysis in the vacuum environment
We optimized the configuration of the N atom in the SA molecule adsorbed on carbon nanotube. It was found that N atom adjacent to the benzene ring adsorbed on carbon nanotubes more stable. At the same time, we also optimized the configurations of two different ring structures of SDZ, SM1, SM2, and SMX molecules adsorbed on carbon nanotube. It was found that benzene rings were more stable when adsorbed on carbon nanotubes. Therefore, we selected the benzene ring, the N atoms on the amino group connected to the benzene ring and O atom on the sulfonamide group for adsorption. The nine stable adsorption configurations of SA on carbon nanotubes are shown in Fig. 2, and the adsorption energy is listed in Table 1. The adsorption configurations of SDZ, SM1, SM2, and SMX are shown in Fig. S1-S4. The adsorption energy and adsorption bond length are listed in Table 1. It is worth emphasize that since the adsorption usually stabilizes the whole system, i.e., lower the total energy, the adsorption energy calculated in this way is negative in most cases. The more negative of the value, the stronger of the adsorption.
As shown in Table 1, from the perspective of adsorption sites, A1-SA has the lowest adsorption energy when the benzene ring of the SA molecule is adsorbed in parallel on carbon nanotubes, and its adsorption distance (2.818 Å) is shorter than A2-SA (2.824 Å) and A3-SA (2.866 Å). Therefore, A1-SA is the most stable adsorption configuration among the three structures. When adsorbed using the O atom of SA, the most stable adsorption energy is -5.18 kcal·mol −1 for B3-SA while adsorbed using the N atom. And when adsorbed using the O atom of SA, the most stable adsorption energy is -5.58 kcal·mol −1 for C3-SA. Compared with the other two adsorption sites of SA, i.e., B and C sites, the A1 adsorption configuration remains to be the most stable one with the lowest adsorption energy of about -10.28 kcal·mol −1 . According to the adsorption energies shown in Table 1, it can be seen that the adsorption of SDZ, SM1, SM2, and SMX is similar. The most stable adsorption sites for them are the A1 configuration. We listed the adsorption configurations of different sulfonamide molecules at different adsorption sites on carbon nanotubes respectively, as shown in Fig. S1-S4. The most stable adsorption configuration of SDZ molecules is A1-SDZ, with an adsorption energy of -13.06 kcal·mol −1 and an adsorption bond length of 2.713 Å. The most stable adsorption configuration of the SM1 molecule is A1-SM1, whose adsorption energy is -12.91 kcal·mol −1 . The most stable adsorption configuration for SM2 is A1-SM2, and its adsorption energy is -13.25 kcal·mol −1 . The most stable adsorption configuration of SMX is A1-SMX, and the adsorption energy is -12.70 kcal·mol −1 . By comparing the adsorption energy of five sulfonamide molecules at various points on carbon nanotubes, as shown in Table 1, we found that the order of adsorption strength of five sulfonamide drug molecules on carbon nanotubes was SM2 > SDZ > SM1 > SMX > SA. As a result, there is a conclusion that of the nine possible adsorption configurations designed, the most stable configuration corresponds to one in which the benzene ring of the drug molecule is adsorbed parallel to the top position of the carbon nanotubes. In order to understand why the benzene ring of drug molecules is the most stable when adsorbed parallel to the top of carbon nanotubes, we calculated the electrostatic potential of five drug molecules and drew the electrostatic potential diagram in Fig. S5. As can be seen, the net negative charges are delocalized in the middle of the benzene ring, which is beneficial for the π-π stacking process. According to the adsorption energy and adsorption bond length calculated before, no matter how the five drug molecules are adsorbed, near the top, bridge, or hollow of carbon nanotubes, the adsorption process is a physical process. The C-C bond length of the carbon six-membered ring in the carbon nanotubes after the sulfonamide adsorption  was still in the range of 1.382-1.453 Å, which also indicates that the carbon nanotubes do not interact with drug molecules chemically to change the bond lengths significantly. The most stable surface of carbon nanotubes on the benzene ring which absorbs drug molecules parallel is related to π-π stacking between the benzene rings of sulfonamide molecules [33][34][35], which is also consistent with the result reported by Gotovac and Zhao [36,37].
To further confirm that the adsorption of carbon nanotubes to five sulfonamide molecules is a physical process, we analyzed the electron density diagram of the adsorption stable configuration. In situations where the charge transfer between two components is significant, i.e., the chemical adsorption, the electron densities of the involved fragments are expected to show obvious overlap. However, such overlap is totally absent in all the systems explored here, implying the interaction between the fragment is small and the charge transfer is negligible. Therefore, the adsorption process belongs to physical adsorption. As shown in Fig. 3, there is nearly no significant overlap among electrons of CNT and the SA molecule when SA molecule is adsorbed on carbon nanotubes in different ways, i.e., A1, B3, and C3 adsorption patterns. This shows that there is no significant electron transfer between drug molecules and carbon nanotubes, which confirms the characteristic of the physical adsorption process. The electron density maps of the other four drug molecules adsorbed on carbon nanotubes are shown in Fig. S6. Similar to SA molecules, these four drug molecules have no electron overlaps. This is consistent with the results of Zhang [38] and Jia et al. [39]. Carbon nanotubes are used for the environmental treatment of sulfonamide in the hope that they can be reused, which requires them to have physical adsorption properties.

Adsorption analysis in the water environment
According to the research results of Tan et al. [40], we have built the adsorption model of five sulfonamide molecules in water environment based on the vacuum stable adsorption model. In the water environment, the adsorption energy and configuration of SA molecules are shown in Table 2 and Fig. 4. The adsorption energy (-14.31 kcal·mol −1 ) of WA1-SA is the lowest and the adsorption bond length (2.806 Å) is the shortest when the benzene ring of the SA molecule is adsorbed in parallel. Therefore, WA1-SA is the most stable adsorption configuration, and WA1-SA is  also the most stable among the nine adsorption configurations. Besides, the configuration of WC3-SA is stable, and its adsorption energy is -11.49 kcal·mol −1 . As shown in Table 1 and Table 2, the order of adsorption strength at different adsorption sites of SA molecule is consistent with that in vacuum. The benzene ring that adsorbs SA parallel is still the most stable one, followed by the N atom and the O atom. As shown in Fig. S7-S10, we depicted the adsorption configurations of different adsorption sites on carbon nanotubes by SDZ, SM1, SM2, and SMX in the water environment. By comparing Table 1 and Table 2, it can be seen that the most stable configuration of the SDZ molecule in the water environment is WA1-SDZ (-15.45 kcal·mol −1 ), which is similar to that in the vacuum environment. The most stable one for the SM1 molecule is WA1-SM1, and the adsorption energy is -15.09 kcal·mol −1 . The most stable SM2 molecule is WA1-SM2, and the adsorption energy is -16.45 kcal·mol −1 . The most stable configuration of SMX molecules is WA1-SMX, and the adsorption energy is -14.72 kcal·mol −1 . By comparing Table 1 and Table 2, it can be found that in the water environment, the adsorption of carbon nanotubes on five drug molecules is stronger, and the absolute value of adsorption energy is larger. In order to understand the stability of five drug molecules in water, It shows that the five drug molecules are more stable in the water environment. This may be due to the introduction of water molecules, resulting in the formation of partial hydrogen bonds between drug molecules and water molecules, soaring the stability of drug molecules in water, and thus improving the adsorption capacity of drug molecules in water. The calculated adsorption energy values of five sulfonamide antibiotic molecules on carbon nanotubes also reflect the physical adsorption characteristics of five sulfonamide molecules on carbon nanotubes in either the vacuum or the water environment.

Adsorption analysis in different acid-base environment
To investigate the effect of carbon nanotubes on the adsorption of sulfonamide molecules in the acid-base environment, we selected the most stable adsorption configuration of five sulfonamide antibiotic molecules in the water environment, which is the configuration of sulfonamides molecules adsorbed parallel to carbon nanotubes with the benzene ring. The adsorption characteristics of five drug molecules in different acid-base environments were studied. AC is the acidic environment with two HCl molecules added, and ac is the acidic environment with one HCl molecule added. The basic environment with one NaOH molecule is represented by alk, and the basic environment with two NaOH molecules is represented by ALK. Now that the acidic and basic molecules are placed near the adsorbed molecules, they can be regarded as strong acidic and basic environment. Moreover, the situations in which two acidic or basic molecules are placed exhibit stronger acid-base property. The adsorption energies of five sulfonamide molecules in the acid-base environment are listed in Table 3. The molecular adsorption configurations in SA environment are shown in Fig. 5, and the adsorption configurations in the acid-base environment of SDZ, SM1, SM2, and SMX are shown in Fig. S11. The adsorption stability of five sulfonamides decreased under different acid-base environment, but the degree of these decreases was different. ac-SA (-5.62 kcal·mol −1 ) has the lowest adsorption energy, and ac-SDZ has the most stable configuration, and its adsorption energy is -7.95 kcal·mol −1 . The adsorption energy of ac-SM1, the most stable configuration, is -6.96 kcal·mol −1 . The adsorption energy of ac-SM2, the most stable configuration, is -8.86 kcal·mol −1 . The most stable configuration of SMX molecule is ac-SMX, and the adsorption energy is -5.95 kcal·mol −1 . In summary, for SA, SDZ, SM1, SM2, and SMX, the adsorption order is as follows: SM2 > SDZ > SM1 > SMX > SA. This is consistent with the results obtained in the vacuum and the water environment. In general, compared with the adsorption energy in the water environment, the adsorption energy in the acid-base environment is decreased and the adsorption stability is weakened. The adsorption energy of sulfonamide adsorbed by carbon nanotubes decreased with the increase of acidity, and similar results were found under basic conditions. In the basic environment, the adsorption capacity of carbon nanotubes to sulfonamide molecules decreases more, which is consistent with the results reported in experimental studies, i.e., the strong acidic or basic environment can be harmful to the adsorption of the sulfoamide molecules [41]. This also means that carbon nanotubes need a proper pH environment for the treatment of sulfonamide molecules.

Conclusions
In this paper, the adsorption characteristics of five sulfonamides on carbon nanotubes under vacuum, neutral water, and different acid and base environments were studied by DFT. According to the adsorption energy, adsorption bond length and electron density diagram, the adsorption type of five kinds of drugs on carbon nanotubes was physical adsorption. By comparing the adsorption energy, the relative stability of five sulfonamide molecules on carbon nanotubes was settled: SM2 > SDZ > SM1 > SMX > SA. The most stable adsorption configuration of the five drugs is that the benzene ring of the drug molecules is adsorbed parallel to the top of the carbon nanotubes. The adsorption energy of five sulfonamide molecules on carbon nanotubes in the water environment is higher than that in the vacuum environment. This may be due to the introduction of water molecules, resulting in the formation of partial hydrogen bonds between drug molecules and water molecules, soaring the stability of drug molecules in water, and thus improving the adsorption capacity of drug molecules in water which indicates that the use of carbon nanotubes in the aqueous environment is more effective in the removal of sulfonamide antibiotics. So the adsorption process is still a physical process without any chemical reactions. The adsorption characteristics of five sulfonamides in various acid-base environments were studied. The adsorption energy of the five drug molecules dwindled significantly in the acid-base environment, and the stronger the acid or basic environment, the more obvious the decline of the adsorption capacity of carbon nanotubes for sulfonamide molecules. This indicates that carbon nanotubes require a suitable pH range to attain the best adsorption performance for the treatment of sulfonamides.