Document Type : Original Research Article
Subjects
Introduction
Nitrazepam (NZ, Fig. 1.), a widely used benzodiazepine derivative, has garnered significant attention due to its therapeutic applications in managing insomnia and anxiety disorders [1]. Its pharmacological efficacy stems from its ability to modulate gamma-aminobutyric acid (GABA) receptors, inducing sedative and hypnotic effects [2]. However, the widespread use of nitrazepam has also raised concerns regarding its environmental presence and potential adverse effects on ecosystems and human health [3]. Residual nitrazepam, often detected in wastewater and surface water, poses challenges due to its persistence, bioaccumulation potential, and toxicity [4]. Consequently, the development of effective strategies for detecting and removing nitrazepam from aqueous environments has become a critical area of research in environmental science and materials chemistry [4]. Traditional methods for detecting and removing pharmaceuticals, including nitrazepam, from water sources often involve techniques such as liquid chromatography [5], advanced oxidation processes [6], or adsorption using activated carbon [2]. While these approaches have shown promise, they are often limited by high operational costs, complex procedures, and incomplete removal efficiency [7]. As a result, researchers have turned to nanotechnology as a viable alternative for addressing these challenges [8]. Nanomaterials, owing to their unique physicochemical properties, high surface area, and tunable reactivity, offer innovative solutions for both sensing and adsorptive removal of contaminants [9]. Among the diverse array of nanomaterials explored, boron nitride (BN) nanoclusters have emerged as a promising candidate due to their exceptional chemical stability, biocompatibility, and adsorption capabilities [10-12]. Boron nitride nanoclusters, specifically the B12N12 cluster (Fig.1.), have attracted considerable interest in recent years for their versatile applications in environmental remediation and molecular sensing [13]. Structurally composed of alternating boron and nitrogen atoms arranged in a cage-like geometry, the B12N12 nanocluster exhibits remarkable electronic properties that make it suitable for interacting with a wide range of organic molecules [14]. The polar nature of the boron-nitrogen bond imparts high affinity toward polar and aromatic compounds, making BN nanoclusters particularly effective for adsorbing pharmaceuticals such as nitrazepam [15]. Furthermore, density functional theory (DFT) simulations have emerged as a powerful computational tool for investigating the molecular interactions between BN nanoclusters and target analytes at an atomic level [16-18]. DFT simulations provide critical insights into adsorption mechanisms, binding energies, charge transfer processes, and electronic structure modifications, enabling researchers to design optimized nanomaterials for specific applications [19-22]. In this study, we aim to explore the potential of the B12N12 nanocluster as an advanced material for nitrazepam detection and adsorptive removal using DFT simulations [23]. By leveraging computational modeling techniques, we seek to elucidate the interaction dynamics between nitrazepam molecules and the BN nanocluster surface [24-26]. Specifically, we focus on understanding the adsorption behavior, electronic structure changes, and thermodynamic feasibility of the interaction [27-30]. The findings from this study are expected to contribute to the development of cost-effective and environmentally sustainable methods for mitigating pharmaceutical contamination in water systems. The significance of this research lies not only in addressing environmental pollution but also in advancing the broader field of nanotechnology-based remediation strategies. By demonstrating the applicability of B12N12 nanoclusters for nitrazepam detection and removal, this study underscores the potential of BN-based materials in tackling emerging contaminants. Moreover, the integration of DFT simulations into materials design highlights the importance of computational approaches in optimizing nanomaterials for real-world applications. As global concerns regarding water quality intensify, innovative solutions such as BN nanoclusters offer a promising pathway toward safeguarding environmental health while fostering interdisciplinary collaboration between chemistry, materials science, and environmental engineering.
The structural design and evaluation of NZ, B12N12, and their combinations were meticulously carried out using GaussView 6 [31] and Nanotube Modeler 1.3.0.3. The procedure commenced with the geometric optimization of each structure to ensure stability and facilitate accurate subsequent analyses. Following optimization, a range of computational analyses was conducted, including infrared (IR) spectroscopy, and frontier molecular orbital (FMO) assessments. The Gaussian 16 software suite [32], known for its robust quantum chemical methodologies, was utilized for computational simulations. Additionally, density of states (DOS) spectra were determined using GaussSum 03. Density Functional Theory (DFT) [33] served as the primary computational approach to study the interaction between sertraline and the boron nitride nanocluster (B₁₂N₁₂). DFT, a quantum mechanical modeling method, calculates electronic structures by solving the Kohn-Sham equations and is particularly effective for examining adsorption processes due to its balance of computational efficiency and accuracy for systems with moderate to large molecular structures. For this study, the 6-31G* basis set [34] was selected for all calculations. This split-valence basis set incorporates polarization functions on heavy atoms, which are crucial for accurately describing electronic distributions and interaction energies in systems involving heteroatoms such as boron and nitrogen. The 6-31G* basis set offers an optimal balance between computational cost and precision, making it suitable for investigating adsorption phenomena on nanoclusters. The exchange-correlation functional employed in this study was the B3LYP [33] hybrid functional, which integrates Becke’s three-parameter exchange functional with the Lee-Yang-Parr correlation functional. The B3LYP functional is widely recognized in computational chemistry for its reliable prediction of molecular properties, including adsorption energies and thermodynamic parameters. Calculations were performed in both gaseous and aqueous phases using the Conductor-like Polarizable Continuum Model (CPCM) to account for solvation effects [35]. Thermodynamic parameters were calculated at three different temperatures: 298 K, 308 K, and 318 K.
The process examined by [35] is as follows:
NZ + B12N12 → NZ-B12N12 (1)
The interaction between NZ and B12N12 was analyzed from various orientations and conformers to identify the most stable configurations. Among the examined conformers, three were determined to be the most stable, as depicted in Fig. 2. In the A-Conformer, the adsorbent is positioned near the Nitro group of NZ. For the B-Conformer, the nanostructure aligns parallel to the benzodiazepine ring of NZ, while in the C-Conformer, B12N12 is situated close to the benzene ring of the adsorbate. Following geometrical optimization across all configurations, it was observed that the nanocluster moved closer to the NZ structure, suggesting a favorable interaction between NZ and B12N12. Additionally, no significant structural distortions were observed during optimization, indicating that the adsorption process is relatively weak and likely characterized as physisorption [36-38]. To further understand the adsorption behavior, the calculated adsorption energies are provided in Table 1. The adsorption energy values for all conformers are negative, confirming the experimental feasibility of NZ interacting with the BN nanocage. Upon closer examination of Table 1, it is evident that the A-Conformer is more favorable compared to B and C due to its more negative total electronic and adsorption energy values [39-43]. The influence of water as a solvent on adsorption energies was also investigated, revealing that while the adsorption energies become less negative in the presence of water, they remain negative overall. This indicates that NZ adsorption is still achievable in an aqueous environment, and water as a solvent does not significantly impact the interactions [44-46]. Additionally, the minimum and maximum calculated IR frequencies, as presented in Table 1, show no negative values, confirming that all analyzed structures correspond to true local minima. Another parameter evaluated was the dipole moment, which, as shown in Table 1, increases substantially after NZ interacts with the BN nanocage. This suggests that NZ-B12N12 complexes are more chemically reactive than the unmodified drug without the nanostructure [47-49].
To better understand the adsorption characteristics, thermodynamic parameters such as ∆Had, ∆Gad, ∆Sad, and Kth were determined for all conformers in both gaseous and aqueous environments at three different temperatures. The findings are summarized in Table 2. The negative values of ∆Had and ∆Gad indicate that the adsorption of NZ on the BN nanocage is exothermic and occurs spontaneously in both gaseous and aqueous phases. However, the negative ∆Sad values suggest that the process is not entropy-favorable, implying that aggregation takes place within the NZ-B12N12 complexes following interaction [40]. Additionally, calculations of thermodynamic equilibrium constants revealed that the adsorption process is fully reversible and exists in an equilibrium state. The influence of temperature on these thermodynamic parameters was also examined, showing that as the temperature rises from 298 K to 318 K, ∆Had and ∆Gad slightly increase, ∆Sad becomes more negative, and Kth decreases significantly. Overall, these results suggest that the adsorption process is more thermodynamically favorable at lower temperatures [41].
The density of states (DOS) spectra for B12N12 and its complexes with NZ are illustrated in Fig. 3. The analysis reveals that the pristine BN nanocage possesses a bandgap of 6.664 eV. However, upon adsorption of NZ onto its surface, the bandgap decreases significantly to 4.093 eV, 3.121 eV, and 3.156 eV for A, B, and C conformers, respectively, corresponding to percentage changes in the bandgap (%∆Eg) of -38.573%, -53.167%, and -52.641%, respectively. This notable reduction in the bandgap of B12N12 after interaction with NZ suggests a substantial enhancement in its electrical conductivity, as conductivity is inversely proportional to the bandgap. Consequently, the BN nanocage demonstrates potential as a sensing material for the electrochemical detection of NZ [42].
Additionally, the chemical hardness of NZ, initially measured at 2.617 eV, decreases to 2.047 eV, 1.560 eV, and 1.578 eV for the A, B, and C conformers upon interaction with the BN nanocage, indicating improved chemical reactivity during the adsorption process. The negative values of chemical potential confirm that these structures are thermodynamically stable and favorable for such interactions. Furthermore, the indices for electrophilicity and maximum charge transfer capacity of NZ show a significant increase after adsorption on the B12N12 surface, highlighting an enhanced tendency of the molecule to accept electrons [43]. This implies that the NZ- B12N12 complexes exhibit greater electrophilic behavior compared to the unmodified NZ molecule, underscoring the potential utility of these complexes in applications requiring heightened electron absorption capabilities [44].
This research delves into the promising potential of the boron nitride nanocluster, specifically B12N12, as an efficient adsorbent and sensor for the removal and detection of the widely used benzodiazepine drug nitrazepam (NZ). By employing advanced density functional theory (DFT) calculations, the study meticulously analyzed the interaction between NZ molecule and the B12N12 nanocluster in various orientations. The findings revealed that B12N12 exhibits a particularly strong affinity for the Nitro group present in NZ, highlighting its selective adsorption capabilities. The calculated adsorption energy values, coupled with negative Gibbs free energy changes and enthalpy changes, unequivocally demonstrated that the interaction is not only experimentally feasible but also thermodynamically favorable, exothermic, and occurs spontaneously under standard conditions. Further investigations explored the influence of external factors such as temperature and the presence of water as a solvent. Results indicated that lower temperatures enhance the adsorption process, while the interaction remains robust and viable even in an aqueous environment, underscoring its practical applicability in real-world scenarios. Additionally, a detailed analysis of the electronic properties of B12N12 revealed significant changes upon NZ adsorption. The pristine nanocluster’s bandgap, initially measured at 6.664 eV, was significantly reduced to 3.121 eV after adsorption, marking a substantial percentage decrease of 53.167%. This reduction in bandgap corresponds to a notable improvement in the material’s electrical conductivity, further enhancing its functionality as a sensor. Collectively, these findings strongly suggest that B12N12 is an excellent candidate for dual applications: as an adsorbent for removing NZ from environments and as a sensitive sensor for detecting its presence.
The authors declare that they have no conflicts of interest related to this work.
