Mitigating Environmental Risks: Efficient Removal of Metronidazole from Pharmaceutical Wastewater Using Functionalized Graphene Membrane ^†

Abstract

Metronidazole, an antibiotic widely used in human and veterinary medicine, poses significant environmental risks when discharged into aquatic environments. This study explores the potential of functionalized graphene membranes for the removal of metronidazole from industrial and pharmaceutical wastewater. Employing molecular simulations and the AM1 semi-empirical-calculation method in solvent (water), we designed and simulated functionalized membranes to enhance metronidazole removal efficiency. Pharmaceutical effluent that contains metronidazole can have detrimental effects on aquatic ecosystems, including toxicity to aquatic organisms and the potential development of antibiotic-resistant bacteria. Our findings show that specific functionalized membranes exhibit selective adsorption for metronidazole, indicating promising results for efficient wastewater treatment. In the study, it was confirmed that a significant drop occurs in the adsorptive property of all functions for metronidazole removal, except for membranes decorated with aldehyde (-CHO) and secondary amine (-CHNH) function. Further analysis of the functionalized graphene membranes confirms one decorated with aldehyde function to have demonstrated superior selective adsorption of metronidazole over water, compared to the other membrane decorated with other functions in the presence of water. The use of functionalized graphene membranes for metronidazole removal shows great potential in mitigating the environmental risks associated with pharmaceutical effluent, which is in line with the study findings and related literature. By improving our understanding of adsorption processes and membrane interactions, we can develop more effective wastewater treatment technologies to safeguard our environment.

1. Introduction

Metronidazole is a commonly prescribed antibiotic, also known as Flagyl, that belongs to the nitroimidazole and anti-bacterial-agents class of medications [1,2,3]. The drug is readily available in both injectable and oral capsule forms, offering flexibility in administration depending on the severity of the infection [3,4]. The drug is primarily used to treat a wide range of gastrointestinal infections, as well as parasitic diseases such as trichomoniasis, giardiasis, and amebiasis. Its broad spectrum of action makes it an essential tool in the treatment of both bacterial and protozoal infections [2,3,4,5].

Despite its effectiveness, metronidazole is not without potential risks. One of the more concerning adverse effects associated with the drug is brain toxicity, which can manifest in a variety of neurological symptoms [6]. These side effects can be particularly alarming when the drug is used for extended periods or in high doses. Furthermore, long-term use of metronidazole or other similar antibiotics has been linked to serious complications such as infertility, adding to the concerns surrounding its prolonged use. Another significant challenge in the use of metronidazole is the potential for abuse [7]. Given its effectiveness and wide availability, metronidazole misuse can lead to complications that are difficult to manage. The toxicity associated with the prolonged or inappropriate use of the drug makes closely monitoring its use crucial, including its discharge from the industrial effluent coming out of the pharmaceutical industry, which is the focus of this report. Many researchers have been exploring measures for improving the treatment and management of pharmaceutical [8,9,10,11] and chemical [12,13,14] effluent wastewater often discharged into our environment, especially ones that contaminate our water bodies and endanger the life of our aquatic animals and thereby exposing our ecosystem danger.

Hence, this study investigates the potential of functionalizing graphene membranes with different selected functional groups (like alcohol, aldehyde, amine, and acid) for removing metronidazole from industrial and pharmaceutical wastewater. Using molecular simulations and the AM1 semi-empirical calculation method in water as the solvent, we designed and simulated functionalized membranes to improve the efficiency of metronidazole removal.

2. Computational Resources and Methodology

The modeling and simulation of metronidazole, water, the graphene membrane, and their interactions were conducted using Spartan 24 (licensed by Wavefunction Inc., US) and the AM1 semi-empirical-calculation method. Initially, the geometry optimization of the structures and interactions explored in the study was performed in a vacuum system using the AM1 method. Subsequently, the optimized structures (shown in Figure 1) were subjected to energy optimization calculations in the presence of a solvent (water), with the resulting energies being recorded as adsorption energies in both vacuum and solvent conditions.

The adsorption energies [11,12,13,14] were computed using a mathematical model (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{a},\mathit{v}\mathit{a}} \mathit{o}\mathit{r} {\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{a},\mathit{a}\mathit{q}}={\mathit{E}}_{\mathit{a},\mathit{x}}-{\mathit{E}}_{\mathit{a}}-{\mathit{E}}_{\mathit{x}}$), where $\mathit{a}\mathit{q}$ is the standing for the aqueous system, $\mathit{v}\mathit{a}$ is the standing for the vacuum system, ${\mathit{E}}_{\mathit{a},\mathit{x}}$ is the total energy of the interacted structure, ${\mathit{E}}_{\mathit{a}}$ is the total energy for the adsorbate, and ${\mathit{E}}_{\mathit{x}}$ is the total energy for the membrane. Figure 2 shows the respective geometrical structure used for the evaluation of the adsorption strength, taking the aldehyde surface as a case. In the study, different material functionalization strategies like alcohol, acid, 1st to 3rd amine, and aldehyde.

3. Results and Discussion

The collated results and findings from the study are presented in this section, highlighting the effect of water on metronidazole adsorption on functionalized graphene membranes and their surface selectivity for metronidazole.

3.1. Effect of Water on Metronidazole Adsorption Strength on Functionalized Graphene Membrane

The impact of adsorbing metronidazole using different graphene membranes decorated with different functional groups, like aldehyde, alcohol, amines, and many other functions in the presence (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{a}\mathit{q}}$) or absence (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{v}\mathit{a}}$) of water as a solvent was investigated. The results obtained from the analysis are presented in

Table 1. The effect of water in metronidazole adsorption on the surfaces (all energies are in eV). Note: Met = Drug, Wat = Water, va = Vacuum system, aq = Aqueous system.

Functionalization	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{v}\mathit{a}}$	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{a}\mathit{q}}$	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t}, \mathit{v}\mathit{a}-\mathit{a}\mathit{q}}$	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t}, \mathit{v}\mathit{a}-\mathit{a}\mathit{q}}$ %
Normal (g-H)	−0.06	0.06	0.12	200.00
Alcohol (g-OH)	−0.36	−0.06	0.3	83.33
Aldehyde (g-CHO)	−0.21	−0.13	0.08	38.10
Acid (g-COOH)	−0.46	−0.23	0.23	50.00
3rd Amine (g-CN)	−0.15	−0.07	0.08	53.33
2nd Amine (g-CHNH)	−0.32	−0.22	0.1	31.25
1st Amine (g-CH2NH2)	−0.19	0.02	0.21	110.53

.

The findings from the results presented in Table 1 indicate that the vacuum adsorption on the metronidazole on the graphene membrane decorated with different function evaluation (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{v}\mathit{a}}$) followed the trend: Acid (−0.46 eV) > Alcohol (−0.36 eV) > 2nd Amine (−0.32 eV) > Aldehyde (−0.21 eV) > 1st Amine (−0.19 eV) > 3rd Amine (−0.15 eV) with reference to the existing literature [12,13,15] that indicated that the more negative the adsorption energy values the stronger interaction and the higher binding force. The results in Table 1 further show that all functions improve the metronidazole adsorption strength (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{v}\mathit{a}}$); however, the carboxylic acid function best improves the performance in a vacuum/gas phase system, unlike other functions that show little adsorption improvement in a vacuum system.

Another analysis of the results collected for the adsorption of metronidazole on the functionalized graphene membrane in Table 1 shows the adsorption strength (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{a}\mathit{q}}$) trend: Acid (−0.23 eV) > 2nd Amine (−0.22 eV) > Aldehyde (−0.13 eV) > 3rd Amine (−0.07 eV) > Alcohol (−0.06 eV) > 1st Amine (0.02 eV). The results show that the ranking of the secondary (2nd) amine and aldehyde improves significantly in the ${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{a}\mathit{q}}$ trend. Further analysis of the adsorption strength of the graphene membranes in the presence of bulk water (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t},\mathit{a}\mathit{q}}$) shows that acid function displayed the highest strength, as shown in Table 1. However, a significant drop in the adsorption strength (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathit{m}\mathit{e}\mathit{t}, \mathit{v}\mathit{a}-\mathit{a}\mathit{q}}$) for the metronidazole was observed for all functions (including the acid function) when the membranes were exposed to bulk water, with the exception of the secondary (2nd) amine and aldehyde, which shows changes lesser than 40 percent (0.08 eV), unlike other functions which lose more than 50 percent of their metronidazole adsorption strength. The findings confirm the secondary (2nd) amine and aldehyde functions (alcohol, carboxylic acid, and 3rd amine) to be more stable in terms of maintaining good adsorption strength for the metronidazole which agreed with the literature [16] that indicated insignificant difference or change for the identified functions on FTIR result of fresh and used activated carbon adsorbent in the study, further confirming low impact of the function on the effective removal of metronidazole.

3.2. The Selectivity of the Surface for Metronidazole over Water Across the Surfaces

Table 2. The surface selectivity of metronidazole over water across the surfaces (all E are in eV). Note: Met = Drug, Wat = Water, va = Vacuum system, aq = Aqueous system.

Functionalization	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$$> {\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$	${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$$-{\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$
Normal (g-H)	0.06	−0.02	FALSE	0.08
Alcohol (g-OH)	−0.06	−0.05	TRUE	-0.01
Aldehyde (g-CHO)	−0.13	−0.03	TRUE	-0.10
Acid (g-COOH)	−0.23	−0.29	FALSE	0.06
3rd Amine (g-CN)	−0.07	−0.03	TRUE	-0.04
2nd Amine (g-CHNH)	−0.22	−0.17	TRUE	-0.05
1st Amine (g-CH2NH2)	0.02	0.07	TRUE	-0.05

presents the results indicating the selectivity of different functionalized graphene membranes for the selective adsorption of metronidazole over the adsorption of water in a bulk system. The relative strength (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$ > ${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$) and the difference (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$ − ${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$) of metronidazole to the water was employed in the analysis as a criterion for evaluating the surface selectivity, in line with existing similar related works [12,13,15] that focused on the removal of specific pollutants from wastewater.

The analysis of the results collected in Table 2 shows the adsorption strength of the functionalized graphene membranes for water (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$) and metronidazole (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$) in the adsorption system in bulk water consistently followed the desired selective adsorption strength (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$ > ${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$) across the functionalized surfaces, with the exception of normal graphene and acid functionalized ones, where the trend was reversed (poor selectivity).

Ranking the selectivity of the surface for the metronidazole over water using the criterion (${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{m}\mathbf{e}\mathbf{t}}$ − ${\mathit{E}}_{\mathit{a}\mathit{d}\mathit{s}}^{\mathbf{w}\mathbf{a}\mathbf{t}}$) indicated their selectivity for metronidazole follows the trend: Aldehyde (−0.10 eV) > 2nd Amine (−0.05 eV) > 1st Amine (−0.05 eV) > 3rd Amine (−0.04 eV) > Alcohol (−0.01 eV) > Acid (0.06 eV). he findings from this trend confirm that the aldehyde-functionalized surface has the best selectivity (its geometrical structure is shown in Figure 3), followed by the amine-functionalized surfaces, which outperform other functions evaluated in the study. These findings show a strong correlation with related carbon materials, such as magnetic activated carbon, in the literature [16], where FTIR analysis often confirms the presence of carbonyl and amine functions as contributive components to the adsorbent surface activity.

4. Conclusions

This study investigates the effect of water on the adsorption strength and selectivity of metronidazole on various functionalized graphene membranes using AM1 semi-empirical calculations. In general, the functionalized graphene outperforms the normal (unfunctionalized) model in terms of adsorption strength and selectivity. Moreover, the findings reveal that the functional groups significantly influence the adsorption behavior, with carboxylic acid exhibiting the highest adsorption strength in a vacuum, while secondary amine and aldehyde groups demonstrate superior stability in aqueous environments, maintaining better adsorption performance compared to other groups. Furthermore, the selectivity of the surfaces for metronidazole over water shows that the aldehyde-functionalized graphene membrane provides the best selectivity, followed by the amine-functionalized ones. These findings suggest that secondary amine and aldehyde-functionalized graphene membranes are promising candidates for selective metronidazole adsorption, particularly in aqueous systems, offering potential applications in pharmaceutical and environmental filtration processes. Further research could focus on optimizing these functional groups for enhanced adsorption capacity, as well as exploring the effects of metronidazole concentration on its adsorption process in practical applications. Future work could also explore the role of metals impregnated in activated carbon (especially magnetic carbon), as used in the literature for metronidazole removal, comparing their impact with that of the functional groups.