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Article

Exploring the Role of Water Molecules in Acetylsalicylic Acid Adsorption Energy on HY Zeolite: A Density Functional Theory Approach

by
Christina Gioti
1,
Dimitrios K. Papayannis
1,* and
Vasilios S. Melissas
2,*
1
Department of Material Science and Engineering, University of Ioannina, GR-451 10 Ioannina, Greece
2
Department of Chemistry, University of Ioannina, GR-451 10 Ioannina, Greece
*
Authors to whom correspondence should be addressed.
AppliedChem 2025, 5(3), 22; https://doi.org/10.3390/appliedchem5030022
Submission received: 30 June 2025 / Revised: 9 August 2025 / Accepted: 22 August 2025 / Published: 11 September 2025
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Abstract

Two different zeolite model clusters were considered in this study to shed light on the release mechanism of a drug, ASA (acetylsalicylic acid), adsorbed on the Y-type zeolite pore walls. Initially, the 3T cluster was employed as a preliminary approach to reveal the trends developed in the acetylsalicylic acid-zeolite system due to the presence of water molecules. Then, the cluster was expanded to 38T (12T:26T), and the adsorption of acetylsalicylic acid in the presence of water molecules inside the pores of the zeolite was studied by employing the hybrid (QM/MM) approximation at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory. The quantum chemical modeling explicitly shows the water molecules’ impact on the value of the adsorption energy. Specifically, the adsorption energy of acetylsalicylic acid gradually decreases from 32.55 kcal mol−1 (in the case of the 38T model cluster with no H2O molecules) to 22.10 kcal mol−1 in the presence of three water molecules.

Graphical Abstract

1. Introduction

Effective drug delivery requires the controlled release of therapeutic agents in optimal amounts, aiming to reduce, limit, or even eliminate potential side effects, which often depend on the dosage form used. Traditional drug formulations frequently result in undesirable adverse effects, such as nausea or diarrhea. However, these side effects can be significantly reduced through the application of advanced drug delivery strategies. In this context, Drug Delivery Systems (DDSs)—including polymer-based systems, mesoporous silicate materials, and others—have demonstrated strong potential as efficient drug carriers. As a result, extensive research has been conducted in recent years to explore and optimize their use in pharmaceutical applications [1,2,3,4,5,6,7,8]. Several studies have recently been reported on exploring the possibility of using zeolites in drug delivery systems [9,10,11,12].
Zeolites and zeolite-based materials exhibit exceptional physical and chemical properties, making them invaluable in a wide range of applications. Their unique structure—consisting of a porous network of molecular-sized channels and cavities—confers remarkable thermal stability, chemical resistance, and tunable active sites. These characteristics, combined with their adsorption and ion exchange capabilities, have established zeolites as critical materials in chemical technology and, increasingly, in pharmaceutical research.
A key advantage of synthetic zeolites for biomedical use is their biocompatibility and low toxicity, along with the ability to improve their physicochemical properties [13,14,15,16]. There are examples of biomedical zeolite applications reported in literature, including imaging, wound healing [17,18,19,20,21,22,23], and drug administration [24,25,26,27,28,29,30,31]. In these examples, different zeolite cations can be exchanged, activated, or provide sites for loading various drug molecules, depending on the specific biomedical application. Recently, the absorption of sulfonamide antibiotics in zeolite Y was investigated [25,26]. The loading and release of anthelmintic and other drugs from zeolites effectively result in controlled release of these molecules [26,29,31,32], e.g., successful in the controlled delivery of ibuprofen [27].
According to reports in the literature, acetylsalicylic acid causes gastrointestinal side effects in several patients [28,29]. Attempts have been made to resolve this problem, such as the simultaneous administration of an antacid, which seems to improve gastrointestinal tolerance to acetylsalicylic acid. An experimental study of the loading and release of acetylsalicylic acid from zeolite HY was carried out by Ashish Datt et al. [30]. This article explains that the acetylsalicylic acid molecule’s molecular dimensions allow it to enter the pores of zeolite Y, interacting with the super cages’ surface, 11.5 Å average diameter. Indeed, acetylsalicylic acid was successfully loaded into the pores of zeolite HY with three different ratios (SiO2/Al2O3) of 5, 30, and 60. HY-5 exhibited nearly complete release of acetylsalicylic acid, while HY-30 and 60 exhibited partial release of acetylsalicylic acid in aqueous solution at pH 7.4. The incomplete release was attributed to the increased hydrophobicity of the higher SiO2/Al2O3 materials, leading to increased van der Waals interactions. This result suggests, first, that water molecules can enter the zeolite pores more easily due to lower SiO2/Al2O3 ratios and, second, that water molecules may play a role in the adsorption energy of acetylsalicylic acid and, by extension, its release, reducing the effects of van der Waals interactions. Recent scientific studies present research papers dedicated to investigating the adsorption properties of biologically active molecules (ibuprofen) on mesoporous silicates. The results of these papers indicate that the presence of water molecules in the silicate plays an important role in the adsorption and release rates of ibuprofen molecules, greatly affecting the adsorption energy [7,8].
However, to optimize and control the loading and release of drug molecules, further research is needed to understand the fundamental interactions between zeolites and drug molecules. In the present study, acetylsalicylic acid was used as a model drug for the theoretical investigation of its adsorption on the inner pore walls of the zeolite crystal system of the faujasite structure, with or without the presence of water molecules. This was done to clarify the role of water in the adsorption energy of acetylsalicylic acid, as well as in its release from the protonated zeolite surface. This was first examined using a 3T linear model (Figure 1a) and then a 38T cluster ring model (Figure 1b), while employing the ONIOM2 (QM/MM) method.
The recent development of hybrid methods, combining quantum mechanics/molecular mechanics (QM/MM) techniques and the more general ONIOM2 method, allows the calculation of reliable results while handling larger model systems with minimal increase in CPU/physical memory consumption. In particular, the two-port ONIOM2 system, which uses a high-level approach for a limited number of tetrahedra and a low-level method, such as MM, for the rest of the complex, has found wide application. Furthermore, the development of new functionals within the density functional theory (DFT) framework, which are more suitably adjusted for the treatment of long-range forces, has provided a new perspective in the theoretical description of systems involving strong dispersion interactions [31,32,33,34]. In the present study, the representation of the high-level of theory was achieved by the hybrid functional HSEH1PBE, in conjunction with the 6-31+G(d,p) basis set [34,35,36,37,38,39]. HSEH1PBE (deciphered as the Heyd-Scuseria-Ernzerhof hybrid combined with Perdew, Burke, and Ernzerhof’s exchange and correlation functions), which is also known as the HSE06 approach, is a second-generation method using a hybrid functional (HSE06) with van der Waals (vdW) interactions and considered suitable for the treatment of noncovalent dispersion forces [40,41,42]. All calculations were carried out by means of the Gaussian 09 Quantum Chemistry Package (Revision D.01) [43].

2. Methods and Computational Details

Two model clusters were used in this study to represent the faujasite cavity and investigate the role of water in the release of acetylsalicylic acid from the zeolite surface. In the first preliminary investigation, density functional theory was implemented by applying the HSEH1PBE functional to the extended basis set of 6-31+G(d,p) to describe the adsorption of the acetylsalicylic acid molecule on the surface of FAU-type zeolite. A simulation cluster containing only three tetrahedra and an acid site of the general form Si2O3H8Al(OHp) was employed, where Hp denotes the protonic hydrogen (Figure 1a). In this calculation, we froze the coordinates of the silicate hydrogen atoms. We optimized the coordinates of all other atoms, namely those of the 3T cluster and the adsorbed acetylsalicylic acid molecule. Despite the small size of these models, such studies have provided valuable insights into the adsorption process and the catalytic mechanism. The 3T model has been applied extensively in the investigation of hydrocarbon heterogeneous reactions on the zeolite surface [43,44,45,46]. It is the smallest size cluster capable of producing a feasible and reliable description of the tendencies and trends governing the reactivity of these systems [44,45,46,47], where the calculated deprotonation energy was in good agreement with the experimental results [48]. However, due to the small size of the clusters employed, the framework effect, which plays an important role in the system’s structure and energetics, is not properly considered. As a result, the contribution of the van der Waals interactions between adsorbed species and the zeolite walls in the energetics of the adsorption/desorption process is often underestimated.
A more accurate picture of the reactivity is naturally expected when a larger cluster is employed [49,50]. To simulate the faujasite HY crystal structure, a 38T zeolite cluster (constructed from thirty-eight tetrahedral zeolite units) was adopted, including one Brønsted acidic hydroxyl site (BAS) called the O1 site. This extended 38T model cluster features two interconnecting rings by a 12-membered ring (MR) window of faujasite zeolite HY [51], with an average diameter of 11.5 Å, corresponding to the molecular formula Si37O56H38Al(OHp), as shown in Figure 1b. The advantage of using an extended model like the 38T relies on its capacity to incorporate further interactions of the adsorbate molecule with the rest O atoms of the ring, in addition to its main interaction with the zeolite active site. Such effects may significantly increase the stabilization energy of the adsorption complex and severely lower the overall potential energy surface, producing an improved picture of the system’s dynamics. Therefore, the use of a larger system is desirable when allowed by available computational resources.
The computational investigation into this second model was carried out using DFT combined with MM techniques within the ONIOM framework. All the 12T ring atoms in the model cluster 12T:26T, along with the acetylsalicylic acid molecules, were treated at the HSEH1PBE(full)/6-31+G(d,p) level of theory. The rest of the model was treated with the Universal Force Field (UFF) approximation to represent the confinement effect of the zeolite pore structure and to reduce the required computational time. All geometries were calculated with a tight geometry optimization criterion.
This particular scheme, employed in the present case, denoted as the two-layer ONIOM2 approximation, initiates from the energy calculation of the active part, E H i g h M o d e l , and further expands to the whole system, E L o w R e a l − E L o w M o d e l , which is supposed to provide an estimate for the total energy, E H i g h R e a l , of the system. The total ONIOM2 energy is provided by the relation:
E O N I O M 2 =   E L o w R e a l + E H i g h M o d e l − E L o w M o d e l ,
where the exponential terms “Real” and “Model” refer to the whole system and the active part, respectively. Similarly, indices “Low” and “High” concern the low and high levels of theory, respectively. ONIOM could be viewed as a hierarchical method gathering both system size and theory accuracy, while approximating an exact calculation on a large molecule [52].
Investigation of the acetylsalicylic acid molecule’s adsorption energy in a hydrated environment and the implication of more than one water molecule participation on the adsorption site was first carried out in the limited 3T cluster, implementing the DFT method, and then in the extended 38T model cluster with the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) methodology. To study the role of water in the release of acetylsalicylic acid from the zeolite surface and to clarify the role of hydrogen bonds in the adsorption energy, we followed a specific methodology. Initially, we calculated the adsorption energy of acetylsalicylic acid in the absence of water molecules while examining two possible orientations of the 3T zeolite cluster (Figure 2). Then, we analyzed the influence of water molecules on the adsorption energy of acetylsalicylic acid. The presence of one water molecule near the active site of the 3T zeolite cluster provides two possible conformations for the adsorbed acetylsalicylic acid molecule (Figure 3), as does the participation of two water molecules, which likewise provides configurations shown in Figure 4a,b, respectively. Specifically, in Figure 4a, the two water molecules interacting with hydrogen bonds create a connection bridge between the adsorbent and the adsorbate through the oxygen atoms O4 and O5, while in Figure 4b, the two water molecules interact while in Figure 4b, the water molecules engage in hydrogen bonding with the tetrahedral oxygen atom O5 of aluminum and the hydroxyl oxygen atom O3 of the ASA molecule.
Regarding the second selected zeolite cluster, namely 38T, the adsorption energy of the acetylsalicylic acid molecule on the zeolite surface as a function of the participating water molecules in the system (adjacent to the ester oxygen) was examined at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory, as shown in Figure 5. In this case, interaction between hydrated and non-hydrated acetylsalicylic acid molecules and the zeolite pore walls for the six encountered models, namely S0–S5, in the presence of 0–5 water molecules, respectively, produces a slightly linear increasing trend in adsorption energy (Figure 6). In contrast, the presence of water molecules near the active site of the zeolite complex led to energetically and thermodynamically more stable conformations and a significant adverse effect on the adsorption energy.
Vibrational frequencies were calculated for the acetylsalicylic acid molecule and the 38T zeolite at the HSEH1PBE/6-31+G(d,p) and the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) levels of theory, respectively.

Intramolecular Interactions

Intramolecular interactions in the acetylsalicylic acid molecule prevent its adsorption on the zeolite surface. Hence, further calculation of the rotational energy barrier of the free acetylsalicylic acid hydroxyl group for the configurations depicted in Figure 7 is considered necessary. The chosen molecular conformation for studying the adsorption phenomenon, where the dihedral O4-C-O3-H2 angle equals 0° (cis configuration), incorporates the global minimum configuration. Our selection is further supported by the available literature experimental data for the pKa constant of 3.49 at 25 °C, which indicates its acidic behavior. Therefore, most acetylsalicylic acid molecules in dissociation form in aqueous solution should allow for significant weakening of intramolecular interactions.
Figure 8 depicts the variation of torsional potential around the C-O3 carboxyl group bond of the free acetylsalicylic acid molecule as a function of the dihedral angle, while implementing a torsional angle scan from 0° to 360° in 30° steps. The energy barrier for hindered rotation around the C-O3 bond was calculated at 11.3 kcal mol−1, high enough to prevent rotation of the hydroxyl group, leading to its second (trans) configuration that favors intramolecular interaction with the ester oxygen. On the other hand, the cis- conformer retains a geometry 3 kcal mol−1 lower than that of the trans-one [53]. Moreover, rotation of the hydroxyl hydrogen around the C-O3 bond, within any available conformation, exhibits alternating energy maxima and minima every 90°.

3. Results and Discussion

3.1. DFT Calculations for the 3T Zeolite Model Cluster-Preliminary Investigation

Initially, the interaction of the acetylsalicylic acid molecule with the 3T cluster was studied in the absence of water molecules to elucidate the role of hydrogen bonds on the adsorption energy, implementing the carboxyl and ester group approach. Geometric parameters of the adsorbed acetylsalicylic acid molecule on the 3T zeolite cluster, when oriented with its acid group in front of the active site and with its ester group ahead, are shown in Figure 2a,b, respectively. The adsorption of the acetylsalicylic acid molecule depicted in Figure 2a appears to be shaped and guided by the cyclic hydrogen bonding complex between the zeolite’s protonic hydrogen and the acetylsalicylic acid oxygen atom, as well as between the acetylsalicylic acid hydroxyl hydrogen atom and the zeolite’s O1. The shift of the vibrational frequencies from 1757 to 1654 cm−1, as well as the lengthening of the O1-Hp bond from 0.965 to 1.043Å (Table 1), indicates an increase in the strength of the interaction. This is also reflected in the adsorption energy (−26.35 kcal mol−1) calculated by Equation (2),
ΔΕadsorption = Εzeolite-acetylsalicylic acid − (Εzeolite + Εacetylsalicylic acid),
On the contrary, in Figure 2b, the absence of a cyclic hydrogen bond complex creates conditions for a looser binding of the adsorbed acetylsalicylic acid and the adsorbent, resulting in a decrease in the interaction energy of more than 12 kcal mol−1 (Table 2).
In detail, the adsorption energy, according to Equation (2) and at the HSEH1PBE/6-31+G(d,p) level of theory, equals −26.3 kcal mol−1 when the acetylsalicylic acid molecule orients its acid group in front of the zeolite cluster’s active site (Figure 2a), while it measures −14.2 kcal mol−1 with its ester group ahead (Figure 2b). Such a significant difference in adsorption energy values between the two aforementioned conformations suggests the initial orientation (acid group-zeolite active site) as the most favorable one.
Next, we studied the complex formed during the adsorption of acetylsalicylic acid in the presence of water molecules. In this case, the contribution of water molecules in the investigated system weakens the cyclic hydrogen bond between the acetylsalicylic acid molecule and the zeolite cluster, thus reducing the adsorption energy and facilitating its release. In detail, we examined two different initial orientations of the water molecule, which resulted in two distinct minimum conformations. In the first configuration, the water molecule approaches the aluminum tetrahedral oxygen atoms. In contrast, in the second configuration, it approaches the interaction region of the acetylsalicylic acid molecule (carboxyl group approach) with the 3T zeolite cluster. The calculated adsorption energy ΔEads of acetylsalicylic acid, with the carboxyl group approach, showed a clear downward trend. Indeed, according to Table 2, the adsorption energy decreases from −26.35 to −19.40 and −22.15 kcal mol−1 for the two configurations, respectively (Figure 3a,b). The redistribution of electronic charge from the formation of new hydrogen bonds also affects the bond distances. Specifically, the bond length of the hydroxyl group in the acetylsalicylic acid molecule, namely r(O3-H2), extents from 0.969 Å, (Figure 7b), to 1.020 Å in the case of ASA within the zeolite cluster, (Figure 2a), and decreases to 1.004 and 1.014 Å for the two acetylsalicylic acid conformations engaged in the zeolite cluster with a single water molecule, (Figure 3a,b).
Similarly, the study of the effect of two water molecules on the complexation energy of acetylsalicylic acid was followed. Again, two different minimum energy configurations were obtained as shown in Figure 4. Τhis energy decreases from −26.35, in the original structure without water molecules (Figure 2a), to −18.71 and −14.09 kcal mol−1 in the two configurations (4a and 4b), respectively. In the second minimum configuration, the cyclic hydrogen bonding complex of acetylsalicylic acid with the zeolite cluster is broken with a simultaneous change of orientation, as depicted in Figure 4b. Τhe acetylsalicylic acid’s adsorption energy to the zeolite, ΔEads, for each of those two configurations, (Table 2) is calculated as follows:
ΔΕads = Εcomplex − Ε(asp‧‧‧H2O) − Ε(zeolite‧‧‧H2O) − Ε(H2O‧‧‧H2O) + 2EH2O,
where Εcomplex is the calculated energy of the acetylsalicylic acid-water-zeolite complex, Ε(asp‧‧‧H2O) is the acetylsalicylic acid-water complex computed energy, Ε(H2O‧‧‧H2O) is the water dimer calculated energy, and EH2O is a single water molecule’s computed energy.
The reduction of the adsorption energy of the acetylsalicylic acid molecule in both configurations in the presence of water molecules is impressive. This needs to be confirmed in a larger simulation model, as it seems that it is not a random, unrealistic result due to the inability to properly approximate the zeolitic environment. In the next section, we describe a different theoretical approach to an extended zeolitic model. However, regardless of the inadequacy of the theoretical results, we consider the recorded trends to be interesting. The aforementioned results were obtained by applying the HSEH1PBE methodology and the 6-31+G(d,p) basis set. Additionally, frozen atoms during geometry optimization were solely the terminal hydrogen atoms of the 3T zeolite cluster.

3.2. Two-Layer ONIOM-Method on the 38T Model Cluster and Water Molecule Effects

Based on the promising results mentioned above, further calculations are considered necessary to reassure the water molecules’ presence effect on the adsorption energy of the acetylsalicylic acid molecule on zeolites. Thus, while the calculated level of theory upgrades to the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) one, we apply to a more realistic standard, which is a thirty-eight tetrahedral (38T) complex with a large ratio on the active site. Figure 1b depicts the optimized geometry of the isolated 38T zeolite model cluster. The good agreement with the reported experimental findings on the faujasite cluster obtained from NMR studies [54,55] supports the reliability of the calculated geometry. For example, the distance between the Al and H atoms of a faujasite Brønsted acid site, Al-Hp, is calculated as 2.401 Å at the above level of theory, which is in close agreement with the experimental value estimated by Freude et al. [54] as 2.38 ± 0.04 Å. The calculated harmonic vibrational frequency of the acidic O1-Hp bond, as 3795 cm−1, is consistent with the reported experimental fundamentals between 3600 and 3623 cm−1 [56,57]. Furthermore, the calculated structure properly demonstrates the effect of the acidic Brønsted site on the neighboring Al-O and Si-O distances. In detail, the bond distance Al-O1 equals 1.849 Å, which connects the Al atom to the oxygen atom holding the protonic Hp, and is substantially extended compared to the Al-O2 distance of 1.712 Å, where O2 denotes the second oxygen atom bonded to the Al one. The same trend holds for the Si-O1 and Si-O2 bond distances, which are equal to 1.706 Å and 1.634 Å, respectively.
The current ONIOM2 model applies to the tetrahedral atoms of the ring, as well as the acetylsalicylic acid and water molecules, while molecular mechanics techniques were used for the lower calculations of the remaining framework atoms. The specific model was initially used to calculate the adsorption energy of the acetylsalicylic acid molecule without any encapsulated water molecules, as shown in Figure 5 (Complex S0), as well as to predict the vibrational spectrum of the complex for comparison purposes with available experimental values. However, our main goal was to investigate, in the extended model of thirty-eight tetrahedra, the effect of water molecules’ presence (near and far from the 3T active site of zeolite, i.e., [≡SiO(Hp)Al(O)2OSi≡]) on the adsorption energy of the acetylsalicylic acid molecule.
The presence of water molecules away from the Brönsted acidic site of the adsorbent produces a slightly linear increasing trend in the adsorption energy of the acetylsalicylic acid molecule due to the polarization of its electronic charge and, thus, a negative influence on its release from the zeolite surface. Figure 5 illustrates all available optimized configurations (S1–S5) in the presence of water molecules, as well as the optimized configuration S0 in the absence of water molecules. The interaction distances confirm the water molecules’ minor effect on the acetylsalicylic acid adsorption energy. This same trend is also depicted in the energy diagram in Figure 6. Indeed, the energy plot exhibits a firm upward trend in the adsorption energy change caused by increasing the water molecules near the ester oxygen of the acetylsalicylic acid molecule. In this case, the polarizing effects of the water molecules on the ASA molecule cause a gradual increase in the interaction between the active part of the zeolite and ASA. However, the relatively large distance from the site of interaction results in a gentle rate of this increase.
Therefore, the effect of water molecules’ participation on the calculation of the acetylsalicylic acid adsorption energy calls for further investigation, either when water molecules approach oxygen atoms on the acetylsalicylic acid carboxyl group or when they reach tetrahedral oxygen atoms of aluminum. As already mentioned, in the case of the 3T model cluster, this investigation produced very interesting results, related to significant changes in the adsorption energy.
After geometry optimization at the desired level of theory, we locate more local minimum configurations, denoted as Ci (i = 1–5) (Figure 9, Figure 10 and Figure 11), of the adsorbed acetylsalicylic acid molecule on the 38T zeolite complex (12T:26T) in the presence of one (C1, C2), two (C3, C4), and three (C5) water molecules, than the corresponding Si ones (Figure 5).
According to Figure 9, optimization reveals two configurations, namely C1 and C2, of the adsorbed acetylsalicylic acid molecule carrying one water molecule on the 38T zeolite complex. The C1 complex presents a water molecule approaching the acetylsalicylic acid carboxyl group oxygen, while in the C2 complex, a water molecule appears reaching the aluminum tetrahedral oxygen atom (Table 3).
Mulliken atomic populations (MAP) give a chemical intuitive representation of charge to each atom in a molecule, being regarded as a qualitative tool for interpreting tendencies about intramolecular charge transfer in a molecular system. Table 4 lists the MAP numbers of the atoms involved in the interaction between zeolite and acetylsalicylic acid for the structures of the S0, C1, and C2 complexes, as well as the bare framework and acetylsalicylic acid molecule. Significant differences between the O1 atom holding the protonic Hp and the O2 atom bonded to the Al atom, as well as between the carboxyl atoms of acetylsalicylic acid O3 and O4, are mentioned. The hydrogen-bonded interaction of the O4 acetylsalicylic acid carboxyl group oxygen atom with the water molecule develops conditions of electronic charge perturbation, resulting in the O2 tetrahedral atom acting as an electron donor with a polarization charge of 0.387e and the hydroxyl hydrogen of acetylsalicylic acid H2 as an electron acceptor with a polarization charge of 0.490e for the C1 complex. Also, the O3 and O4 carboxyl oxygen atoms of acetylsalicylic acid acquire a more negative charge than the corresponding ones for complexes S0 and C2. On the contrary, in complex C2, the interaction of the aluminum tetrahedral oxygen on the zeolite with the water molecule displays a greater polarization charge of 0.486e on the O2 atom, similar to that on O2 (0.492e) for the S0 complex. This insignificant difference in the value of the polarization charge of the O2 atom, as well as O1, O3, and O4 atoms for complexes S0 and C2, is consistent with their complexation energy. It is therefore useful to compare the polarization charge of the O2 in the isolated zeolite cluster (0.982e) with the corresponding polarization charges of the O2 atom for complexes S0 (0.492e), C1 (0.387e), and C2 (0.486e). Indeed, the polarization charge on the S0, C1, and C2 complexes is proportional to their complexation energy, S0 (−32.55 kcal mol−1), C1 (−28.52 kcal mol−1), and C2 (−30.83 kcal mol−1). Similar behavior was identified for the hydroxyl hydrogen atom H1 of acetylsalicylic acid, which acts as an electron donor. The corresponding polarization charge was calculated as +0.536e for the C0 complex, whereas values of +0.490e and +0.532e were determined for the C1 and C2 complexes, respectively. This difference in the polarization charge of the tetrahedral and carboxyl oxygen atoms for configurations C1 and C2, relative to that of the bare zeolite framework (38T), justifies the findings, which are reflected in Table 3 and Table 5. The first conformation C1 in Figure 9 shows a looser bond between the acetylsalicylic acid molecule and the zeolite framework since the adsorption energy of the C1 complex reduces by about 4 kcal mol−1 compared to that of the S0 (Table 5). This decrease should be due to the reduction of the positive charge on the zeolite’s oxygen atom O2, which causes a weakening of the hydrogen bond with the acetylsalicylic acid hydroxyl hydrogen atom. Afterwards, H1 exhibits a corresponding reduction of its positive charge. In general, quantum chemical modeling showed a considerable effect of water molecules on the alteration of the adsorption energy. More specifically, from −32.55 kcal mol−1 for acetylsalicylic acid, complexation energy decreased to −28.52 and −30.83 kcal mol−1 for the two complexes C1 and C2, respectively, in the presence of one water molecule, to −26.01 and −28.09 kcal mol−1 for complexes C3 and C4, individually, in the presence of two water molecules, and to −22.10 kcal mol−1 in the presence of three water molecules for complex C5.
Selected bond distances presented in Table 3 further support our findings. Specifically, the hydrogen bond length in complex C1, O2-H1, is 1.020 Å, while in complexes C2 and S0 becomes equal to 1.381 and 1.372 Å, respectively. The structure of complex C1 better resembles the free adsorbed acetylsalicylic acid molecule and the adsorbent geometry rather than the conformation of complexes S0 and C2. This indicates a weaker interaction between the adsorbent and the adsorbed molecule and therefore a looser bond. We also notice a negligible difference in the bond distance between the zeolite’s protonic hydrogen Hp and the carboxylic oxygen O4 for complexes C1 and C2. The hydrogen bond length for the C1 complex, O1-Hp, equals 1.427 Å, while for the C2 one, it becomes 1.411 Å.
C3 complex geometry was significantly disrupted due to the presence of two water molecules, as shown in Figure 10. The protonic hydrogen, Hp, of zeolite appears to have retreated entirely from the vicinity of the tetrahedral O1 atom, significantly expanding the O1-Hp distance to 1.553 Å. At the same time, it approaches the oxygen of the water molecule, almost losing its interaction with acetylsalicylic acid. On the other hand, acetylsalicylic acid interacts with the zeolite’s tetrahedral O2 atom only through the hydroxyl hydrogen of its carboxyl group at a distance of 1.721 Å, which is much longer than the 1.372 Å distance in the absence of water molecules. In brief, the acetylsalicylic acid molecule is nearly detached from a zeolite’s site and remains attached to the other one. This favors breaking the cyclic hydrogen bond, resulting in a significant weakening of the interaction, which further reduces the absorption energy to −26.01 kcal mol−1. Moreover, we locate a C4 conformation with two water molecules (Figure 10), which better resembles the C2 configuration, as does the corresponding adsorption energy. Specifically, the energy decreases from −32.55 kcal mol−1 in the absence of water molecules in complex S0 to −28.09 kcal mol−1 in the presence of two water molecules in complex C4. Three water molecules in the C5 complex appear to have the greatest impact on the adsorption energy, since it decreases to −22.10 kcal mol−1 from −32.55 kcal mol−1 in the S0 complex, representing a reduction exceeding 10 kcal mol−1, as shown in Figure 11. Table 5 records this significant reduction in the adsorption energy of acetylsalicylic acid on zeolite with water molecules enclosed, which may significantly contribute to its release. This result is also demonstrated in the energy diagram in Figure 12.

Vibrational Frequencies

The zeolite absorption spectra exhibit reasonable agreement between theoretical harmonics and experimental fundamentals. The characteristic vibrational bands of the zeolite framework appear in both spectra (Figure 13). The calculated vibrational frequency of the acidic O1-Hp bond, at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory for the 38T cluster, remains consistent with experimental findings for the H-FAU.
More specifically, the broad band in the experimental IR spectrum of faujasite in a hydrated environment (with relatively high water loadings arising from the air during the experimental process) at approximately 3600 cm−1, which is due to the stretching vibrations of the adsorbed water molecules and vibrations assigned to the counterion Hp cations with the zeolite lattice oxygens (O1-Hp bond vibrations), appears to be slightly shifted in the theoretical spectrum due to anharmonicity. Computed harmonic vibrational frequencies are typically larger than the experimentally observed fundamentals, due to the neglect of anharmonic effects, the incorporation of electron correlation, and the use of a finite basis set [57,58,59].
As shown in Figure 13, a small shoulder appears in the experimental spectrum at 1095 cm−1 at lower frequencies, whereas in the calculated spectrum, it forms a low-intensity peak. Nevertheless, the peak (or shoulder) at 1095 cm−1 is mainly due to the internal linkages between SiO4 and AlO4 tetrahedra of the zeolite [58,59]. The high-intensity band at 1003 cm−1 is due to the overlap of the asymmetrical vibrations between bridging (Si-O) and non-bridging (Si-O-) Si-O bonds [60]. Moreover, in both spectra, lower frequency bands, which appear at 557 cm−1 and 465 cm−1, are attributed to symmetrical stretching of the external linkages and bending vibrations of the Si-O bonds, respectively [58,59,61]. Finally, in the experimental spectrum, a low-frequency band at 667 cm−1 appears as a slightly shifted peak in the calculated spectrum. This band could be assigned to Al-O vibrations [60] or to symmetrical stretching of the internal tetrahedra [58,62].
Experimental and theoretical FTIR absorption spectra of acetylsalicylic acid are provided in Figure 14. The experimental spectrum manifests the characteristic vibrational peaks of the free acetylsalicylic acid molecule. At high frequencies, the broad bands in the vibrational region of 2554 to 3488 cm−1 are attributed to the carboxylic acid in the liquid and solid phases, due to hydrogen bonding (O-H stretching vibrations) [63,64]. At lower frequencies, the high-intensity peaks at 1606 and 1685 cm−1 are assigned to the -C=O double bond of the carboxylic group. According to the literature, the ring carbon-carbon stretching vibration occurs in this particular region, forming two or three bands due to skeletal vibration, and is usually more intense [63,64,65]. Peaks in the vibrational region of 1305 to 1481 cm−1 are due to the C-O stretching vibrations, while peaks from 754 to 1219 cm−1 are due to the C-H vibrations. More specifically, peaks from 1016 to 1219 cm−1 are assigned to the in-plane deformation due to the C-H vibration, while peaks from 754 to 918 cm−1 are assigned to the out-of-plane deformation [63,66]. Finally, the low-frequency peaks at 511, 603, and 668 cm−1 occur due to the C-H bending vibrations, aromatic in-plane ring rocking, and aromatic out-of-plane ring deformation, respectively [63,64]. The theoretical FTIR spectrum of the free acetylsalicylic acid molecule strongly agrees with the experimental one, but it involves certain alterations, such as the one correlated to the stretching asymmetric vibration frequency of the carbonyl group, νasCOO-. This particular peak is shifted by about 72 cm−1, from 1685 (experimental frequency) to 1757 cm−1 (calculated frequency). Also, an important deviation between the experimental and theoretical values occurs in the symmetric stretching vibration frequency νsCOO-, i.e., 1481 (experimental) and 1383 cm−1 (calculated). Such deviations easily account for anharmonicity effects, which are not accounted for in theoretical values. On the other hand, the decrease in the stretching vibrational frequency of the -C=O double bond in the adsorbed acetylsalicylic acid molecule, compared to the free one, is 205 cm−1 (from 1757 cm−1 in the free acetylsalicylic acid molecule to 1552 cm−1 in the adsorbed form) (Table 3). This decrease is fully justified due to its strong interaction with the active part of the 38T zeolite complex. This is consistent with the smaller frequency shift of 103 cm−1 (from 1757 cm−1 in the free acetylsalicylic acid molecule to 1654 cm−1 in the adsorbed form), for the 3T model, as shown in Table 1, where the interaction was found to be weaker by 6.2 kcal mol−1.

4. Conclusions

To expand our understanding of important processes, such as drug delivery and the degradation of drugs by excipients, accurate structures and energy values of drugs interacting with the zeolite surface must be precisely known. The present work reports the first all-electron density functional characterization based on a hybrid functional of a drug, namely acetylsalicylic acid, confined in a realistic model of zeolite material to investigate in depth the effect of the presence of water molecules on the adsorption energy of acetylsalicylic acid. The acetylsalicylic acid molecule, having smaller dimensions than those of the pores of the HY zeolite, enters its inner surface and interacts with the zeolite’s active site, forming a cyclic hydrogen bond complex. Nevertheless, the theoretically calculated high adsorption energy (approximately 32.5 kcal mol−1) does not justify its release, as has been experimentally established, in aqueous solution at pH 7.4. On the other hand, the intramolecular forces within the acetylsalicylic acid molecule may prevent its binding to the zeolite surface, since the hydroxyl hydrogen is internally oriented. Therefore, a preliminary test is useful and necessary. The study of the hydroxyl group rotation barrier in the acetylsalicylic acid molecule showed that this interaction could not reduce the acidity of the acetylsalicylic acid molecule. The calculated rotation energy barrier of 13 kcal mol−1 is sufficiently high to prevent the hydroxyl group from rotating, thereby stabilizing it in its second (cis) configuration. This is further supported by the literature value of the pKa constant, which equals 3.49, at 25 °C, indicating that it is an acidic drug. Those preliminary results led us to further investigate the mechanism of acetylsalicylic acid release and how it occurs, despite the strong binding of acetylsalicylic acid to the active site of the zeolite, as shown by our theoretical calculations. Hence, our research focused on the effect of water molecules on the adsorption energy. Implementing the HSEH1PBE/6-31+G(d,p) and the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) methods, respectively, on the 3T and 38T(12T:26T) model clusters, the physical adsorption of acetylsalicylic acid on the zeolite surface in the presence of water molecules was studied. In both cases, results indicated that water molecules’ participation in configurations approaching the active part of the zeolite has a significant impact on the adsorption energy. More specifically, as the water molecules approach the active part of the zeolite, the most stable structures are created, where the adsorption energy of acetylsalicylic acid gradually decreases from 32.55 kcal mol−1, as is the case of the 38T model cluster, to 22.01 kcal mol−1 in the presence of three water molecules, as in the case of complex C5. Those results demonstrate the crucial role of water molecules in the release mechanism of acetylsalicylic acid from zeolites.

Author Contributions

Conceptualization, D.K.P.; Methodology, D.K.P.; Validation, V.S.M.; Formal analysis, V.S.M.; Investigation, D.K.P.; Data curation, C.G.; Writing—original draft, C.G.; Writing—review & editing, D.K.P.; Supervision, V.S.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. (a) The 3T zeolite cluster at the HSEH1PBE/6-31+G(d,p) level of theory. (b) The 38T zeolite cluster at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
Figure 1. (a) The 3T zeolite cluster at the HSEH1PBE/6-31+G(d,p) level of theory. (b) The 38T zeolite cluster at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
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Figure 2. Structures of adsorbed ASA molecule on the 3T zeolite cluster oriented (a) with its acid group in front of the active site and (b) with its ester group in front of the active site, both structures at the HSEH1PBE/6-31+G(d,p) level of theory.
Figure 2. Structures of adsorbed ASA molecule on the 3T zeolite cluster oriented (a) with its acid group in front of the active site and (b) with its ester group in front of the active site, both structures at the HSEH1PBE/6-31+G(d,p) level of theory.
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Figure 3. Configurations (a,b) of adsorbed ASA molecule on the 3T zeolite cluster, bearing a single water molecule in the active site, at the HSEH1PBE/6-31+G(d,p) level of theory.
Figure 3. Configurations (a,b) of adsorbed ASA molecule on the 3T zeolite cluster, bearing a single water molecule in the active site, at the HSEH1PBE/6-31+G(d,p) level of theory.
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Figure 4. Configurations (a,b) of adsorbed ASA molecule on the 3T zeolite cluster, bearing two water molecules in the active site, at the HSEH1PBE/6-31+G(d,p) level of theory.
Figure 4. Configurations (a,b) of adsorbed ASA molecule on the 3T zeolite cluster, bearing two water molecules in the active site, at the HSEH1PBE/6-31+G(d,p) level of theory.
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Figure 5. Interaction details between ASA and zeolite pore walls for the six, namely S0–S5, 38T cluster models bearing 0–5 water molecules away from the active site.
Figure 5. Interaction details between ASA and zeolite pore walls for the six, namely S0–S5, 38T cluster models bearing 0–5 water molecules away from the active site.
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Figure 6. The ASA molecule’s adsorption energy on the zeolite surface as a function of the water molecules’ number in the system environment (near the ester oxygen) at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
Figure 6. The ASA molecule’s adsorption energy on the zeolite surface as a function of the water molecules’ number in the system environment (near the ester oxygen) at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
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Figure 7. The two most stable (energetically equivalent) configurations of the ASA molecule, at the HSEH1PBE/6-31+G(d,p) level of theory, exhibit a very small energy difference of 0.95 kcal mol−1. (a) The hydroxyl group is as far away from the ester group. (b) The hydroxyl group is on the side of the ester functional group.
Figure 7. The two most stable (energetically equivalent) configurations of the ASA molecule, at the HSEH1PBE/6-31+G(d,p) level of theory, exhibit a very small energy difference of 0.95 kcal mol−1. (a) The hydroxyl group is as far away from the ester group. (b) The hydroxyl group is on the side of the ester functional group.
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Figure 8. Torsional potential around the C-O3 bond of the ASA molecule’s carboxyl group vs. O4CO3H2 dihedral angle.
Figure 8. Torsional potential around the C-O3 bond of the ASA molecule’s carboxyl group vs. O4CO3H2 dihedral angle.
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Figure 9. The adsorbed ASA molecule on the 38T (12T:26T) zeolite cluster, in the presence of a single water molecule near the active site, leading to configuration C1 (the water molecule resides in the back of the figure) and configuration C2 (the water molecule settles in front of the figure) at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
Figure 9. The adsorbed ASA molecule on the 38T (12T:26T) zeolite cluster, in the presence of a single water molecule near the active site, leading to configuration C1 (the water molecule resides in the back of the figure) and configuration C2 (the water molecule settles in front of the figure) at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
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Figure 10. The adsorbed ASA molecule on the 38T (12T:26T) zeolite cluster, in the presence of two water molecules near the active site, leading to configuration C3 and configuration C4 at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
Figure 10. The adsorbed ASA molecule on the 38T (12T:26T) zeolite cluster, in the presence of two water molecules near the active site, leading to configuration C3 and configuration C4 at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
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Figure 11. The adsorbed ASA molecule on the 38T (12T:26T) zeolite cluster, in the presence of three water molecules near the active site, leading to configuration C5 at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
Figure 11. The adsorbed ASA molecule on the 38T (12T:26T) zeolite cluster, in the presence of three water molecules near the active site, leading to configuration C5 at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF level of theory.
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Appliedchem 05 00022 g012
Figure 12. Adsorption energy values (ΔEads), including Zero Point Energy (ZPE) corrections, in kcal mol−1, of the acetylsalicylic acid molecule on the 38T zeolite cluster as a function of the water molecules’ number in the system environment (near the active site), at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
Figure 12. Adsorption energy values (ΔEads), including Zero Point Energy (ZPE) corrections, in kcal mol−1, of the acetylsalicylic acid molecule on the 38T zeolite cluster as a function of the water molecules’ number in the system environment (near the active site), at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
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Appliedchem 05 00022 g013
Figure 13. Comparison between the calculated theoretical IR spectra of the 38T cluster, while employing the HSEH1PBE/6-31+G(d,p) level of theory, and the experimental FTIR absorption spectra of the H-FAU.
Figure 13. Comparison between the calculated theoretical IR spectra of the 38T cluster, while employing the HSEH1PBE/6-31+G(d,p) level of theory, and the experimental FTIR absorption spectra of the H-FAU.
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Figure 14. Comparison between the calculated theoretical IR spectra of free acetylsalicylic acid, computed at the HSEH1PBE/6-31+G(d,p) level of theory, and the experimental FTIR absorption spectra of ASA.
Figure 14. Comparison between the calculated theoretical IR spectra of free acetylsalicylic acid, computed at the HSEH1PBE/6-31+G(d,p) level of theory, and the experimental FTIR absorption spectra of ASA.
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Table 1. Selected optimized bond distances (Å) and vibrational frequencies (cm−1) of the 3Τ cluster, the acetylsalicylic acid, and the 3T-ASA-xH2O (x = 0, 1, 2) complexes at the HSEH1PBE/6-31+G(d,p) level of theory.
Table 1. Selected optimized bond distances (Å) and vibrational frequencies (cm−1) of the 3Τ cluster, the acetylsalicylic acid, and the 3T-ASA-xH2O (x = 0, 1, 2) complexes at the HSEH1PBE/6-31+G(d,p) level of theory.
Bond
Lengths		Cluster
3T		Acetylsalicylic
Acid (ASA)		Complex1
3T-ASA		Complex2
3T-ASA-1H2O		Complex3
3T-ASA-2H2O
O1-Hp0.965------1.0431.045 a
1.013 b		1.033 c
1.085 d
O2-H2------------1.5491.566 a
1.601 b		1.658 c
1.655 d
O4-Hp------------1.4271.422 a
1.544 b		1.461 c
4.653 d
O3-H2------0.9691.0201.004 a
1.014 b		1.005 c
1.004 d
Al-Hp2.464
2.38 ± 0.04 e		-----------------------------
Frequencies
νasCOO-		 17571654
a,b Optimized bond distances for configurations a and b, respectively, in Figure 3. c,d Optimized bond distances for configurations a and b, respectively, in Figure 4. e From Ref. [54].
Table 2. Adsorption energy values (ΔEads), including Zero Point Energy (ZPE) corrections, in kcal mol−1, of the acetylsalicylic acid molecule on the plain 3T zeolite cluster (Complex 1, 3T-ASA) and the hydrated 3T-xH2O (x = 1, 2) complexes (Complex 2 and 3, 3T-ASA-xH2O, x = 1, 2), at the HSEH1PBE/6-31+G(d,p) level of theory.
Table 2. Adsorption energy values (ΔEads), including Zero Point Energy (ZPE) corrections, in kcal mol−1, of the acetylsalicylic acid molecule on the plain 3T zeolite cluster (Complex 1, 3T-ASA) and the hydrated 3T-xH2O (x = 1, 2) complexes (Complex 2 and 3, 3T-ASA-xH2O, x = 1, 2), at the HSEH1PBE/6-31+G(d,p) level of theory.
SpeciesComplex1
3T-ASA		Complex2
3T-ASA-1H2O		Complex3
3T-ASA-2H2O
ΔEads−26.35−19.40 a, −22.15 b−18.71 c, −14.09 d
ΔEads−14.05 e--------------
a,b Adsorption energy values for configurations a and b (carboxyl group approach), respectively, in Figure 3. c,d Adsorption energy values for configurations a and b (carboxyl group approach), respectively, in Figure 4. e Adsorption energy value via the ester group approach in Figure 2b.
Table 3. Selected optimized bond distances (Å) and vibrational frequencies (cm−1) of the 38Τ cluster, the acetylsalicylic acid, and the 38T-ASA-xH2O (x = 0, 1, 2, 3) complexes at the ONIOM2//HSEH1PBE/6-31+G(d,p):UFF level of theory.
Table 3. Selected optimized bond distances (Å) and vibrational frequencies (cm−1) of the 38Τ cluster, the acetylsalicylic acid, and the 38T-ASA-xH2O (x = 0, 1, 2, 3) complexes at the ONIOM2//HSEH1PBE/6-31+G(d,p):UFF level of theory.
Bond
Lengths		Cluster
38T		Acetylsalicylic
Acid (ASA)		Complex1
3T-ASA		Complex2
3T-ASA-1H2O		Complex3
3T-ASA-2H2O		Complex4
3T-ASA-3H2O
O1-Hp0.968 1.3801.427 a, 1.411 b1.553 c, 1.549 d1.533
O2-H1------ 1.3721.020 a, 1.381 b1.721 c, 1.056 d1.717
O3-H1------0.9681.0811.553 a, 1.076 b1.006 c, 1.422 d
O4-Hp-------------1.0731.061a, 1.061 b2.886 c, 1.019 d2.923
Al-Hp2.401
2.38 ± 0.04 e
2.48 ± 0.04 e
2.43 ± 0.03 e		-----------------------------------
Frequencies
νasCOO		 17571552
a,b Optimized bond distances for configurations C1 and C2, respectively, in Figure 9. c,d Optimized bond distances for configurations C3 and C4, respectively, in Figure 10. e From Ref. [54].
Table 4. Mulliken Atomic Populations for atoms in (i) the free acetylsalicylic acid molecule at the HSEH1PBE/6-31+G(d,p) level of theory, and (ii-a) the bare zeolite framework and (ii-b) the hydrogen-bonded complexes S0, C1, and C2, with all zeolite structures treated at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
Table 4. Mulliken Atomic Populations for atoms in (i) the free acetylsalicylic acid molecule at the HSEH1PBE/6-31+G(d,p) level of theory, and (ii-a) the bare zeolite framework and (ii-b) the hydrogen-bonded complexes S0, C1, and C2, with all zeolite structures treated at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
MAP (e)
AtomsFragmentsComplex S0
38T-ASA		Complex C1
38T-ASA-1H2O		ComplexC2
38T-ASA-1H2O
38TASA
O1−0.935 −0.449−0.434−0.448
O2−0.982 −0.49−0.387−0.486
O3 −0.504−0.392−0.411−0.394
O4 −0.458−0.502−0.522−0.503
Hp+0.524 +0.531+0.526+0.524
H1 +0.407+0.536+0.490+0.532
Table 5. Adsorption energy values (ΔEads), including Zero Point Energy (ZPE) corrections, in kcal mol−1, of the acetylsalicylic acid molecule on the plain 38T zeolite cluster (Complex 1, 38T-ASA) and the hydrated 38T-xH2O (x = 1, 2, 3) complexes (Complex 2, 3 and 4, 38T-ASA-xH2O, x = 1, 2, 3), at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
Table 5. Adsorption energy values (ΔEads), including Zero Point Energy (ZPE) corrections, in kcal mol−1, of the acetylsalicylic acid molecule on the plain 38T zeolite cluster (Complex 1, 38T-ASA) and the hydrated 38T-xH2O (x = 1, 2, 3) complexes (Complex 2, 3 and 4, 38T-ASA-xH2O, x = 1, 2, 3), at the ONIOM2//(HSEH1PBE/6-31+G(d,p):UFF) level of theory.
SpeciesComplex1
38T-ASA		Complex2
38T-ASA-1H2O		Complex3
38T-ASA-2H2O		Complex4
38T-ASA-3H2O
ΔEads−32.55−28.52 a−26.01 c−22.10
ΔEads-------−30.83 b−28.09 d-------
a,b Adsorption energy values for configurations C1 and C2, respectively, in Figure 9. c,d Adsorption energy values for configurations C3 and C4, respectively, in Figure 10.
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Gioti, C.; Papayannis, D.K.; Melissas, V.S. Exploring the Role of Water Molecules in Acetylsalicylic Acid Adsorption Energy on HY Zeolite: A Density Functional Theory Approach. AppliedChem 2025, 5, 22. https://doi.org/10.3390/appliedchem5030022

AMA Style

Gioti C, Papayannis DK, Melissas VS. Exploring the Role of Water Molecules in Acetylsalicylic Acid Adsorption Energy on HY Zeolite: A Density Functional Theory Approach. AppliedChem. 2025; 5(3):22. https://doi.org/10.3390/appliedchem5030022

Chicago/Turabian Style

Gioti, Christina, Dimitrios K. Papayannis, and Vasilios S. Melissas. 2025. "Exploring the Role of Water Molecules in Acetylsalicylic Acid Adsorption Energy on HY Zeolite: A Density Functional Theory Approach" AppliedChem 5, no. 3: 22. https://doi.org/10.3390/appliedchem5030022

APA Style

Gioti, C., Papayannis, D. K., & Melissas, V. S. (2025). Exploring the Role of Water Molecules in Acetylsalicylic Acid Adsorption Energy on HY Zeolite: A Density Functional Theory Approach. AppliedChem, 5(3), 22. https://doi.org/10.3390/appliedchem5030022

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