Jean Wilfried Hounfodji

Wilfried G Kanhounnon

Gaston Kpotin

Guy S Atohoun

Juliette Lainé

Yann Foucaud

Michael Badawi

Molecular insights on the adsorption of some pharmaceutical residues from wastewater on kaolinite surfaces

Keywords: DFT, clay, aspirin, paracetamol, ibuprofen, diazepam

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Wastewaters contain a wide range of chemical products [START_REF] Stackelberg | Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds[END_REF] among which more than 55 pharmaceuticals over the 150 daily used in significant amounts worldwide are present in significant concentrations [START_REF] Sui | Occurrence, sources and fate of pharmaceuticals and personal care products in the groundwater: A review[END_REF][START_REF] Huerta-Fontela | Occurrence and removal of pharmaceuticals and hormones through drinking water treatment[END_REF]. They are used for various applications, including anticancers, anti-biotics, anti-inflammatory, anxiolytic…, and are particularly concentrated in hospital sewage [START_REF] Yessoufou | Pharmaceuticals and Personal Care Products (PPSPS) in the Aquatic Environment: Status and Issues in the Republic of Benin[END_REF]: among the common 55 above-mentioned drugs, around 35 are found in concentrations up to 1200 ng/L [START_REF] Huerta-Fontela | Occurrence and removal of pharmaceuticals and hormones through drinking water treatment[END_REF]. In particular, aspirin, paracetamol -or acetaminophen -, ibuprofen, diclofenac (all common anti-inflammatory drugs), diazepam, and carbamazepine (well-known antiepileptic medications) represent the most used and, therefore, the most discarded compounds. Most of them are categorized as essential by the World Health Organization (WHO) in its 21 st Essential Medicines List. Each year, about 40,000 tons of aspirin are consumed worldwide under the form of around 120 billion 300-mg tablets [START_REF] Chandrasekharan | COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression[END_REF]. In France, 260 million paracetamol doses are used each year, which makes this molecule one of the most consumed of the country; in the USA, in 2017, it was the 25 th most recommended medicine, representing over 24 million prescriptions. Studies in source waters from a US drinking water treatment plant showed that carbamazepine was detected in 92% of the samples and acetaminophen in 75% [START_REF] Stackelberg | Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds[END_REF], while both compounds were detected in a Chinese effluent [START_REF] Lin | Occurrence, removal and risk assessment of pharmaceutical and personal care products (PPCPs) in an advanced drinking water treatment plant (ADWTP) around Taihu Lake in China[END_REF] or in various countries in Europe (with concentrations higher than 13 ng.L -1 for carbamazepine) [START_REF] Huerta-Fontela | Occurrence and removal of pharmaceuticals and hormones through drinking water treatment[END_REF]. The bioaccumulation of these molecules represents a serious ecotoxicological risk and causes severe sanitary threats such as organisms antibioresistance, metabolisms disruptions, bacteria strains proliferation, and various other pathologies [7,[START_REF] Schreurs | Interaction of Polycyclic Musks and UV Filters with the Estrogen Receptor (ER), Androgen Receptor (AR), and Progesterone Receptor (PR) in Reporter Gene Bioassays[END_REF]. If they have disastrous effect on the fauna, such as fish feminization phenomena [START_REF] Gross-Sorokin | Assessment of Feminization of Male Fish in English Rivers by the Environment Agency of England and Wales[END_REF], renal lesions, and gills alteration of fishes exposed to diclofenac [START_REF] Poiger | Photodegradation of the pharmaceutical drug diclofenac in a lake: pathway, field measurements, and mathematical modeling[END_REF], humankind can also be strongly affected through water drinking or halieutic products consuming. Antiepileptic medications like carbamazepine can be neuroteratogenic [START_REF] Olney | Environmental agents that have the potential to trigger massive apoptotic neurodegeneration in the developing brain[END_REF], that is, analgesic overdoses of such compounds may cause severe -even fatal -skin reactions and an overconsumption of aspirin and/or paracetamol can also cause severe chronic failures or gastric ulcers [START_REF] Fored | Acetaminophen, Aspirin, and Chronic Renal Failure[END_REF][START_REF] Duggan | Progress report. Aspirin in chronic gastric ulcer: an Australian experience[END_REF][START_REF] Zhu | Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications[END_REF].

They can also cause strong allergic reactions as well as a habituation making their use pointless.

A drinking water plant usually follows a process route with different chemical removing techniques: chlorination (disinfection), ozone treatment, and/or sand and GAC (Granular Activated Carbon) filtration [START_REF] Stackelberg | Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds[END_REF][START_REF] Huerta-Fontela | Occurrence and removal of pharmaceuticals and hormones through drinking water treatment[END_REF]. However, they are generally poorly efficient, especially for the removal of the aforementioned molecules from sewage, since they are not well-adapted for their specific treatment. For instance, a study conducted on more than 113 compounds from water and sediments from a drinking-water plant showed than carbamazepine was detected in all the studied end-of-process water samples, which meant that this molecule was not completely removed from the water [START_REF] Stackelberg | Efficiency of conventional drinking-water-treatment processes in removal of pharmaceuticals and other organic compounds[END_REF][START_REF] Huerta-Fontela | Occurrence and removal of pharmaceuticals and hormones through drinking water treatment[END_REF] and, therefore, rejected in nature. Another study, realized on 5 European countries, demonstrated that, albeit more than 90% of the total amount of ibuprofen is removed, only 39% of the total amount of diclofenac is extracted [START_REF] Paxéus | Removal of selected non-steroidal anti-inflammatory drugs (NSAIDs), gemfibrozil, carbamazepine, b-blockers, trimethoprim and triclosan in conventional wastewater treatment plants in five EU countries and their discharge to the aquatic environment[END_REF]. To the best of our knowledge, the processes behind the molecules removal is poorly understood and, although hypotheses might be assumed, no real conclusions are offered; hence, finding a good depolluting route to process all the aforementioned chemicals is yet to be proposed. Besides, the presence of all the pharmaceuticals together in the environment, on top of increasing their toxicity, may influence their removal [START_REF] Brausch | A review of personal care products in the aquatic environment: Environmental concentrations and toxicity[END_REF]. Various techniques -physical, chemical, and biological -already exist and have been developed for the depollution of wastewaters in terms of pharmaceuticals [START_REF] De Andrade | Adsorption of Pharmaceuticals from Water and Wastewater Using Nonconventional Low-Cost Materials: A Review[END_REF][START_REF] Gadipelly | Pharmaceutical Industry Wastewater: Review of the Technologies for Water Treatment and Reuse[END_REF][START_REF] Bhadra | Adsorption of diclofenac sodium from water using oxidized activated carbon[END_REF][START_REF] Shamsudin | Fabrication and characterization of a thin coated adsorbent for antibiotic and analgesic adsorption: Experimental investigation and statistical physical modelling[END_REF]. However, they all display various sanitation efficiency degrees along with significant limitations, mainly entailed by high process costs and the generation of more-or-less dangerous by-products. Among all the above-mentioned processes, the adsorption appears to be the most efficient method to remove pollutants from sewage [START_REF] Arica | Poly(dopamine) grafted bio-silica composite with tetraethylenepentamine ligands for enhanced adsorption of pollutants[END_REF][START_REF] Arica | Magnetic MCM-41 silica particles grafted with poly(glycidylmethacrylate) brush: Modification and application for removal of direct dyes[END_REF][START_REF] Bayramoglu | Removal of reactive dyes from wastewater by acrylate polymer beads bearing amino groups: isotherm and kinetic studies[END_REF][START_REF] Bhatnagar | Application of Adsorbents for Water Pollution Control[END_REF][START_REF] Bhadra | Adsorptive removal of ibuprofen and diclofenac from water using metal-organic framework-derived porous carbon[END_REF][START_REF] Khalil | Selective Capture of Phenol from Biofuel Using Protonated Faujasite Zeolites with Different Si/Al Ratios[END_REF][START_REF] Khalil | Biofuel purification: Coupling experimental and theoretical investigations for efficient separation of phenol from aromatics by zeolites[END_REF][START_REF] Azambre | Effects of the cation and Si/Al ratio on CH3I adsorption by faujasite zeolites[END_REF]. Among all the materials that were investigated as adsorbents, activated carbon is currently the most adsorptive and used [START_REF] Bhadra | Adsorption of diclofenac sodium from water using oxidized activated carbon[END_REF][START_REF] Bhadra | Adsorptive removal of ibuprofen and diclofenac from water using metal-organic framework-derived porous carbon[END_REF][START_REF] Li | Adsorption of hazardous dyes on functionalized multiwalled carbon nanotubes in single and binary systems: Experimental study and physicochemical interpretation of the adsorption mechanism[END_REF][START_REF] Fierro | Adsorption of phenol onto activated carbons having different textural and surface properties[END_REF], including in water treatment plants (GAC filtration).

Nonetheless, its preparation and regeneration are generally significantly expensive, which decreases their overall accessibility [START_REF] Crini | Sorption processes and pollution: conventional and non-conventional sorbents for pollutant removal from wastewaters[END_REF]. On the other hand, clay materials are cheap and extremely abundant, since they are naturally formed by the alteration and weathering of rocks.

They are, along with aluminosilicates [START_REF] Zadaka | Modified silicates and porous glass as adsorbents for removal of organic pollutants from water and comparison with activated carbons[END_REF][START_REF] Li | Adsorption of ibuprofen on organo-sepiolite and on zeolite/sepiolite heterostructure: Synthesis, characterization and statistical physics modeling[END_REF], thoroughly investigated as potential pollutant adsorbents [START_REF] Srinivasan | Advances in Application of Natural Clay and Its Composites in Removal of Biological, Organic, and Inorganic Contaminants from Drinking Water[END_REF][START_REF] Bentahar | Adsorptive properties of Moroccan clays for the removal of arsenic(V) from aqueous solution[END_REF][START_REF] Uddin | A review on the adsorption of heavy metals by clay minerals, with special focus on the past decade[END_REF][START_REF] Elmoubarki | Adsorption of textile dyes on raw and decanted Moroccan clays: Kinetics, equilibrium and thermodynamics[END_REF][START_REF] Szabó | New Insights on the Simultaneous Removal by Adsorption on Organoclays of Humic Acid and Phenol[END_REF]. Interestingly, they display large specific surfaces, high ion exchange capacities, good adsorption properties, and an absence of toxicity, which make them materials of choice for the removal of pollutants from wastewaters. In particular, kaolinite [Al2Si2O5(OH)4] has been widely investigated for the adsorption of various types of molecules such as phenol, pesticides, dyes, etc., for their removal [START_REF] Dehmani | Chemical characterization and adsorption of oil mill wastewater on Moroccan clay in order to be used in the agricultural field[END_REF][START_REF] Alkaram | The removal of phenol from aqueous solutions by adsorption using surfactant-modified bentonite and kaolinite[END_REF][START_REF] Polati | Sorption of Pesticides on Kaolinite and Montmorillonite as a Function of Hydrophilicity[END_REF][START_REF] Nabbou | Removal of fluoride from groundwater using natural clay (kaolinite): Optimization of adsorption conditions[END_REF]. Kaolinite is a common component of soils and kaolinite deposits are very common on all continents, which induces its significant availability and its low cost. Therefore, understanding the mechanisms involved in the adsorption of pharmaceuticals on kaolinite is of paramount interest to enhance the wastewaters depolluting processes and to propose new perspectives of low-cost and efficient water treatments routes.

To the best of our knowledge, the adsorption mechanisms of the above-mentioned chemicals on kaolinite are poorly understood and documented. Nonetheless, this information is hardly accessible by experiments and, therefore, we suggest the use of atomistic simulations to shed light on this scientific problematic. Among the various existing computational methods, density functional theory (DFT) provides a good compromise between cost calculation and accuracy [START_REF] Hafner | Ab-initio simulations of materials using VASP: Density-functional theory and beyond[END_REF][START_REF] Foucaud | A review of atomistic simulation methods for surface physical-chemistry phenomena applied to froth flotation[END_REF]. This theory is widely used to study adsorption phenomena in various systems [START_REF] Chibani | Impact of the Si/Al ratio on the selective capture of iodine compounds in silver-mordenite: a periodic DFT study[END_REF][START_REF] Foucaud | Molecular Insight into Fatty Acid Adsorption on Bare and Hydrated (111) Fluorite Surface[END_REF][START_REF] Chibani | A DFT study of RuO4 interactions with porous materials: metal-organic frameworks (MOFs) and zeolites[END_REF][START_REF] Jabraoui | Adsorption of volatile organic and iodine compounds over silver-exchanged mordenites: A comparative periodic DFT study for several silver loadings[END_REF][START_REF] Berro | Atomistic description of phenol, CO and H2O adsorption over crystalline and amorphous silica surfaces for hydrodeoxygenation applications[END_REF] and is, nowadays, one of the most used in material science. In particular, the adsorption of various molecules as water on kaolinite (and clays in general) has already been intensively investigated using quantum mechanical simulations [START_REF] Underwood | Wetting Effects and Molecular Adsorption at Hydrated Kaolinite Clay Mineral Surfaces[END_REF][START_REF] Chen | Experimental investigation and DFT calculation of different amine/ammonium salts adsorption on kaolinite[END_REF] and it has been clearly demonstrated that they can give real insights of the occurring mechanisms. This work aims, first, at identifying and accurately characterizing the adsorption modes of the aforementioned medical compounds on kaolinite and, second, at comparing the adsorption energies between those molecules to identify eventual competitions in their adsorption. With this investigation, we aim at offering new insights in the adsorption of common medical molecules at a molecular scale and at opening new perspectives for the environmental sciences by using theoretical atomistic tools.

Material and methods

Structural model

Kaolinite (Al2Si2O5(OH)4), part of phyllosilicate minerals group, was used for this study. A primitive cell with lattice parameters a = 5.15 Å, b = 8.94 Å, c = 7.39 Å, α = 91.93°, β = 105.05°, and γ = 89.80° [START_REF] Bish | Rietveld Refinement of Non-Hydrogen Atomic Positions in Kaolinite[END_REF] was fully relaxed by DFT and used to generate a 2x2x2 supercell. The kaolinite bulk is formed by a repetition of silicon tetrahedra (SiO4) layers and aluminum octahedra (AlO6) layers along the c-axis [START_REF] Deng | Effect of structural stress on the intercalation rate of kaolinite[END_REF], see Figure 1. Each aluminum octahedron contains two hydroxyl groups, which establish H-bonds with oxygen atoms of the silica tetrahedra. This ensures the stability of the crystal structure by bonding the silica tetrahedra layers to the aluminum octahedra layers. The 2x2x2 supercell was fully relaxed by DFT and used to generate a (001) surface, which, considering the weakness of H-bonds that link the silica tetrahedra to the aluminum octahedra, is the most exposed cleavage plane [START_REF] Deer | An Introduction to the Rock-Forming Minerals[END_REF]. This also explains the presence of two types of surfaces for kaolinite: an aluminol (hydroxylated due to the presence of the hydrogen atoms) surface and a siloxane (non-hydroxylated) surface (Figure 2). To avoid any interaction between the adsorbed molecules and the periodic image of the slab, a vacuum of 20 Å was systematically added along the c direction (Figure 2).

Molecules

The six molecules considered hereafter are presented in Table 1 as well as in Figure 3. They were all relaxed by DFT calculations in vacuo conditions before being placed at the vicinity of the surface.

DFT calculation settings

DFT calculations were performed using the Vienna Ab initio Simulation Package (VASP) [START_REF] Kresse | Ab initio molecular dynamics for liquid metals[END_REF]. The semi-local exchange-correlation functional of Perdew-Burke-Ernzrhof (PBE) in the general gradient approximation (GGA) [START_REF] Grimme | Semiempirical GGA-type density functional constructed with a long-range dispersion correction[END_REF] was used [START_REF] Perdew | Generalized gradient approximation made simple[END_REF]. The electron-ion interactions were described using the Projected Augmented Wave (PAW) method [START_REF] Kresse | From ultrasoft pseudopotentials to the projector augmented-wave method[END_REF] and Kohn-Sham equations were solved self-consistently with a convergence criterion of 10 -6 eV. After a convergence analysis, the cut-off energy was set to 450 eV. The ionic relaxation was systematically conducted until all the forces applied on each atom were smaller than 0.02 eV/A. Considering the large size of the cells, the integration of the Brillouin zone was performed using the Γ-point only. Furthermore, to describe accurately the adsorption mechanisms of the different considered molecules, dispersion interactions were evaluated using the D2 method of Grimme [START_REF] Grimme | Semiempirical GGA-type density functional constructed with a long-range dispersion correction[END_REF][START_REF] Grimme | Accurate description of van der Waals complexes by density functional theory including empirical corrections[END_REF].

The adsorption energies, as well as the dispersion energies, of the different molecules on kaolinite surfaces, ∆Eads, were calculated using the total energies of the sole kaolinite slab, Ekao, of the sole molecule, EX, and of the system where the molecule is adsorbed on the kaolinite surface, Ekao-X, as follows:

(1) ∆Eads = Ekao-X -Ekao -EX

The Bader charges (Q) were also computed [60][START_REF] Tang | A grid-based Bader analysis algorithm without lattice bias[END_REF][START_REF] Henkelman | A fast and robust algorithm for Bader decomposition of charge density[END_REF][START_REF] Sanville | Improved grid-based algorithm for Bader charge allocation[END_REF]. For a given molecule, the Bader charge of each atom was evaluated before and after the adsorption, i.e. when the molecule is alone in vacuum phase and when the molecule is adsorbed on the kaolinite surface, respectively. Also, the difference in terms of electronic charge, ΔQ, was computed (Eq. 2) and allowed us to assess the contribution of each atom to the adsorption as well as the possible charge transfers between the molecule and the surface [START_REF] Bader | Atoms in molecules: a quantum theory[END_REF][START_REF] Tang | A grid-based Bader analysis algorithm without lattice bias[END_REF][START_REF] Sanville | Improved grid-based algorithm for Bader charge allocation[END_REF][START_REF] Henkelman | A fast and robust algorithm for Bader decomposition of charge density[END_REF]:

(2)

∆Q = Q / - /
where Q / is the Bader charge of the atom A of the molecule adsorbed on kaolinite and / is the Bader charge of the same atom of the molecule in vacuo condition. Moreover, the variations of the electron density (Δρ) induced by the adsorption were calculated following Eq. 3 and subsequently visualized using the VESTA software [START_REF] Momma | VESTA : a three-dimensional visualization system for electronic and structural analysis[END_REF]:

(3) Δρ = ρ -ρ -ρ
where , , and are the electron densities of the sole kaolinite slab, of the sole molecule, and of the system where the molecule is adsorbed on the kaolinite slab, respectively. On all the figures, the represented electron density variation iso-surface indicates a variation of 0.004 electron/Å -3 before and after the adsorption, which corresponds to typical hydrogen bonds [START_REF] Klein | Electron Density Topological Analysis of Hydrogen Bonding in Glucopyranose and Hydrated Glucopyranose[END_REF].

Results and discussion

Molecules adsorption

All the studied molecules were placed on the aluminol and siloxane kaolinite surfaces in both vertical and flat configurations, to assess the most favored adsorption mode in vacuum. The adsorption energies are displayed in Table 2.

The adsorptions of all the considered molecules, whatever their configuration, are exothermic.

In almost all cases, the exothermic aspect of the molecule adsorption can be attributed to the significant contribution of dispersion interactions (Table 2). In addition, all the molecules adsorb more favorably on the aluminol surface rather than on the siloxane surface. Therefore, the aluminol surface is expected to adsorb most pollutants, although the two surfaces should exist in equal proportions when kaolinite is cleaved. Based on these results, the adsorption mechanisms of each molecule have been studied only on the aluminol surface hereafter, particularly in terms of geometries and electron densities. In the vertical configuration, PAR adsorbs by establishing two hydrogen bonds between its terminal hydroxyl group and two surface hydroxyl groups of kaolinite (Figure 4a) while the rest of the molecule does not interact with the surface. Besides, when PAR is adsorbed in a flat configuration, several hydrogen bonds are established between the molecule and the surface. The two main bonds occur between the PAR hydroxyl group and a surface oxygen atom with d = 1.58 Å and between the oxygen atom of the amide group and a surface hydroxyl group with d = 1.80 Å (Figure 4b). The existence of these two bonds is confirmed by the electron density changes (Figure 4c), which allows the identification of an additional hydrogen bond, between the terminal methyl group and a surface oxygen atom with d = 2.2 Å. Furthermore, Bader charges display no charge transfer between the surface and the molecule (Table S1), which is consistent with the sole presence of hydrogen bonds that only rely on electronegativity differences.

Ibuprofen (IBU)

As PAR, IBU adsorbs with lower adsorption energies on aluminol surface than on siloxane surface, for both configurations. On the former, the flat adsorption is significantly favored In vertical configuration, IBU adsorbs by two hydrogen bonds established between the molecule carboxylic group and a surface oxygen atom/hydroxyl group (Figure 5a). The rest of the chain does not interact with the surface. In flat configuration, the most favored one, the oxygen atom of the carboxyl group forms one hydrogen bond with a surface hydroxyl group with d = 1.8 Å (Figure 5b). However, other hydrogen bonds are present between some surface oxygen atoms and the non-aromatic hydrogen atoms of the molecule (Figure 5c). As for PAR,

Bader charges indicate no electron transfer between IBU and the surface (Table S1), which is consistent with the adsorption through hydrogen bonds and π interactions.

Carbamazepine (CAR)

CAR adsorbs most favorably in a vertical configuration on the aluminol surface with an energy of ΔEads = -137.7 kJ.mol -1 including ΔEdisp = -51.7 kJ.mol -1 (contribution of 38%), which is slighly lower than for the flat configuration that exhibits ΔEads = -127.1 kJ.mol -1 including ΔEdisp = -92.6 kJ.mol -1 (representing 73%). CAR adsorbs through hydrogen bonds, which are established between the nitrogen and oxygen atoms of the carbamoyl group and the surface hydrogen atoms with d = 1.9 Å and d = 1.8 Å, respectively (Figure 6a). In addition, two other hydrogen bonds are created between the closest-to-the-surface CH group from the two external benzoic cycles and two surface oxygen atoms (Figure 6c), which is confirmed by the electron density changes induced by the adsorption. They share one oxygen atom of the surface (located at 2.6 and 2.8 Å of the considered atoms) and are also bonded to their one oxygen (d = 2.1 and d = 2.6 Å). Besides, considering the significant contribution of the dispersion forces for the flat adsorption, no bond is observed for the flat adsorption (Figure 6b). Overall, the calculation of Bader charges confirms the absence of any electron transfer (Table S1), which is consistent with the sole presence of hydrogen bonds for the vertical adsorption and of dispersive interactions for the flat adsorption.

Aspirin (ASP)

On the aluminol surface, ASP adsorbs in the vertical configuration with ΔEads = -46.2 kJ.mol -1 including ΔEdisp = -31.3 kJ.mol -1 (68%) while the flat adsorption occurs with ΔEads = -115.1 kJ.mol -1 including ΔEdisp = -98.2 kJ.mol -1 , which represents 85% of the overall energy. Considering the considerable contribution of dispersion energy in the total adsorption energies, the adsorption of ASP is mainly controlled by dispersive interactions. In vertical configuration, the C-H from the terminal methyl group however establishes a hydrogen bond with a surface oxygen atom (Figure 7a). Besides, in flat configuration, the two oxygen atoms of the ester group form hydrogen bonds with surface hydrogens with d = 2.4 and 2.3 Å (Figure 7b). The two oxygen atoms of the carboxylic group also establish hydrogen bonds with three surface hydrogen atoms with d = 2.2 Å, 2.5 Å, and 2.7 Å, respectively, which is confirmed by the electron density differences (Figure 7c). Dispersive interactions probably include the interactions between the C=C from the molecule cycle and hydrogen atoms from the surface, which exhibit an average distance of 2.2 Å (Figure 7b). The differences in Bader charges calculated before and after the adsorption are negligible (see Table S1), which is consistent with the interactions involved in the present case.

Diclofenac (DIC)

DIC is most favorably adsorbed on the aluminol surface in a flat configuration with ΔEads = -114.2 kJ.mol -1 including ΔEdisp = -114.5 kJ.mol -1 while, in the vertical configuration, it adsorbs with an energy of -88.0 kJ.mol -1 with a dispersion contribution of -47.6 kJ.mol -1

(representing 54% of the overall energy). In vertical configuration, a hydrogen bond with d = 2 Å is formed between the oxygen atom of the carboxyl group with a surface hydrogen while the -OH of the carboxyl group points away from the surface (Figure 8a). This bond is also observed for the flat configuration (Figure 8b) along with a hydrogen bond established between a chlorine atom from the dichlorophenyl cycle and a surface hydrogen atom (Figure 8b) with d = 2.3 Å, which is possible considering the significant difference of electronegativities of Cl and H (3.2 and 2.2, respectively). Meanwhile, a weak hydrogen bond, only observable with electron density changes (Figure 8c), is formed between a surface oxygen and the amino phenyl group of the molecule. Another hydrogen bond links a C-H group of the ethanoic termination of DIC with a surface oxygen atom, with d = 2.0 Å (Figure 8c). Bader charges calculation does not exhibit any electron transfer between the two systems (Table S1), which is consistent with the adsorptions by sole hydrogen bonds.

Diazepam (DIA)

Like all the other studied molecules, DIA is most favorably adsorbed on the aluminol surface.

Flat adsorption is more stable than vertical adsorption since ΔEads = -96.8 kJ.mol -1 including ΔEdisp = -113.5 kJ.mol -1 against ΔEads = -70.9 kJ.mol -1 including ΔEdisp = -39.kJ.mol -1 , respectively. Interestingly, the dispersion contribution is significantly lower than the total adsorption energy for the flat adsorption, indicating the existence of steric repulsion. DIA is adsorbed on (001) kaolinite surface by hydrogen bonds. In vertical configuration, the oxygen atom of the carbonyl group establishes two hydrogen bonds with two different surface hydrogen atoms (Figure 9a). However, in flat configuration, this atom points away from the surface and DIA adsorbs by means of a hydrogen bond between its chlorine atom and a surface hydrogen atom (Figure 9b), with d = 2.2 Å. Another interaction exists between a C-H group of the cycle and a surface oxygen atom with d = 2.1 Å. Also, very weak hydrogen bonds can be observed on the electron density variations (Figure 9c), which also confirm the two aforementioned bonds. Additionally, Bader charges calculations demonstrate no electron transfer between the surface and the molecule (Table S1), which is consistent with the adsorption by hydrogen bonds only.

Comparison between all molecules

Based on the adsorption energies values, the six molecules can be classified from the most strongly adsorbed to the less strongly adsorbed, i.e. from the lower adsorption energy to the highest: paracetamol > ibuprofen > carbamazepine > aspirin > diclofenac > diazepam. Table 3 summarizes the adsorption energies and the dispersion contributions of the most favored configurations. Interestingly, for the two less strongly adsorbed molecules -diclofenac and diazepam -the cause of the exothermic behavior of the adsorptions solely comes from the dispersion interactions, which contribution is equal or superior to 100%. This can be attributed to the presence of chlorine atoms in the molecules that make the polar component of the adsorption energy positive, and also to some global steric repulsion between the surface and the molecule. Besides, the molecules can be classified from the one exhibiting the lowest dispersion contributions to the one with the highest dispersion contribution: carbamazepine < paracetamol < ibuprofen < aspirin < diclofenac < diazepam. Dispersive interactions play an important role (except for the carbamazepine) since their order of magnitude is the same than that of the overall adsorption energies. The presence of chlorine atoms seems to decrease the polar component of the adsorption energy in absolute values, which induces that the adsorption is mostly based on dispersion interactions.

Competition with water

Since the main objective of this study is to investigate the removal of the six considered molecules from water, the whole process is mandatorily conducted in hydrated conditions.

Therefore, water molecules are most probably pre-adsorbed on kaolinite surfaces and can significantly compete with the pharmaceutical molecules' adsorption. Hence, we also investigated the adsorption of a single water molecule on the kaolinite surfaces. Water adsorbs more preferably on the aluminol surface with an adsorption energy of -90.6 kJ.mol -1 including a dispersion contribution of -18.7 kJ.mol -1 compared to the siloxane surface, which exhibits an adsorption energy of -23.4 kJ.mol -1 including a dispersion contribution of -11.0 kJ.mol -1 . These results are consistent with the literature: some authors reported that the aluminol surface is hydrophilic while the siloxane one is hydrophobic [START_REF] Šolc | Wettability of kaolinite (001) surfaces -Molecular dynamic study[END_REF][START_REF] Chen | Mechanism research on surface hydration of kaolinite, insights from DFT and MD simulations[END_REF][START_REF] Tunega | Ab Initio Molecular Dynamics Study of a Monomolecular Water Layer on Octahedral and Tetrahedral Kaolinite Surfaces[END_REF]. Among all the studied molecules, water presents the lowest adsorption energy in absolute value for both surfaces. Therefore, it will theoretically not represent a competition for the adsorption of the other molecules, except for diazepam on the aluminol surface, where the adsorption energy is close to that of water.

Evaluation of the risk of by-product formation

During the adsorption process, the formation of residual and undesirable by-products might occur, which could put into question the whole removal process [START_REF] Hessou | A first principle evaluation of the adsorption mechanism and stability of volatile organic compounds into NaY zeolite[END_REF][START_REF] Hessou | Dibenzyl Disulfide Adsorption on Cationic Exchanged Faujasites: A DFT Study[END_REF]. Indeed, the reactivation of the adsorbent may be difficult or represent a danger due to the liberation of byproducts that could be more dangerous than the initial pharmaceutical products.

To prevent the formation of those residual by-products during the adsorption, the bonds of the adsorbed molecules must not be activated throughout the process. Therefore, one can assess the risk of by-product formation by monitoring the variation of intramolecular bonds lengths during the adsorption [START_REF] Hessou | Adsorption of NO, NO2, CO, H2O and CO2 over isolated monovalent cations in faujasite zeolite: a periodic DFT investigation[END_REF]. Table S2 gather intramolecular distances of pharmaceutical molecules before and after adsorption on kaolinite surfaces. The intramolecular O-H bonds are the most affected during the molecule adsorption on the (001) kaolinite aluminol surface.

Their evolution upon adsorption is presented in Figure 11. From the bonds lengths variations study, we can conclude that (Figure 11):

O-H bonds in ASP is elongated of 0.021 Å during the adsorption process, which could lead to an acidification of the environment by a proton liberation. It is consistent with the acid-base nature of ASP induced by the carboxylic group that can liberate a proton.

Basically, this should not represent a problem since the pKa of ASP is reported around 3.5, as many other carboxylic acids, which means that, at neutral pH, ASP is already under its anionic form. This could significantly increase the ASP adsorption energies on kaolinite since our calculations considered only the acidic form.

O-H bond in PAR is extended from 0.01 to 0.06 Å on respectively aluminol and siloxane surfaces. However, the liberation of a proton is unlikely to occur since the formation of an alcoholate would require a considerable activation energy, solely attained for high pH values (> 14).

Overall, a shortening of all other targeted bonds has been exhibited, which mean that they are not activated.

Based on the aforementioned results and discussions, the adsorption of all the considered molecules on kaolinite presents no risk of by-product formation. Therefore, kaolinite could be applied to the hospital sewage depollution for the removal of the six considered molecules.

Material regenerability

The adsorbate regeneration after pollutant adsorption for its reuse is an important concern that may be considered. Thus, we calculated the free adsorption enthalpies (ΔG) of the six studied molecules on the kaolinite aluminol surface at different temperatures using thermodynamic corrections based on partition functions as used in [START_REF] Badawi | DFT study of furan adsorption over stable molybdenum sulfide catalyst under HDO conditions[END_REF][START_REF] Badawi | Guaiacol derivatives and inhibiting species adsorption over MoS2 and CoMoS catalysts under HDO conditions: A DFT study[END_REF][START_REF] Kanhounnon | Quantum mechanistic study of furan and 2-methylfuran hydrodeoxygenation on molybdenum and tungsten sulfide clusters[END_REF]:

(4) ΔrG°(T)= ΔEads + ΔZPE + ΔH + ΔH !" + ΔH -T(ΔS + ΔS !" + ΔS )

where ΔEads is the adsorption energy at 0 K, ΔZPE the zero-point energy, ΔHvib and ΔSvib the vibrationnal enthalpy and entropy, ΔHtrans and ΔStrans the translational enthalpy and entropy, and ΔHrot and ΔSrot the rotational enthalpy and entropy. By considering the involvement of the adsorbed molecules in a motionless complex, one can neglect the translation and rotation components [START_REF] Humbert | Competitive adsorption of nitrogen and sulphur compounds on a multisite model of NiMoS catalyst: A theoretical study[END_REF]. Besides, the vibration terms are assumed to roughly compensate each other before and after the adsorption reaction, which induces that ΔSvib = 0. Consequently, we can write Eq. 5 and Eq. 6.

(

) ΔZPE = $%& (6) ΔrG° (T) = ΔEads + $%& -[' ( ) (X) + ' ( (X)] -T [+ ( ) (X) ++ ( (X)] 5
The different terms of Eq (6) are determined from the following equations [START_REF] Jensen | Introduction to Computational Chemistry[END_REF]:

ZPVE = R 1 ℎ3 25 67 8
9:

(7) H = R 1 ℎ3 5 1 ? @A B / C -1 (8) 67 8

9:

H !" = E F GH (9)
H = 6 F GH for non linear molecule [START_REF] Poiger | Photodegradation of the pharmaceutical drug diclofenac in a lake: pathway, field measurements, and mathematical modeling[END_REF] where R is the constant of perfect gas, h is the Planck constant, k is the Boltzmann constant, vi is a vibration frequency computed with the harmonic approximation, T is the temperature.

We aimed at estimating the temperatures corresponding to the adsorbate desorption, i.e. when the free enthalpy of the system reaches 0 and changes of sign. The molecule desorption begins at 448 K for PAR, at 323 K for ASP, at 350 K for CAR and at 360 K for IBU. The adsorption free enthalpies of DIC and DIA reach 0 at temperatures below 298 K, which means that, at ambient temperature, these molecules are lowly adsorbed. This is consistent with the DFT calculations results, which exhibit lower adsorption energies of those two molecules compared to the other studied molecules, particularly DIA, whose adsorption is less favored than water. The thermal agitation attained at 360 K should enable kaolinite to discharge its pollutant while only water would still be adsorbed on the clay mineral (T(ΔGwater=0) = 523 K), which is not an issue since, to be reused, the hydrated material would be in contact again with aqueous effluents.

Conclusion

The theoretical study of organic pollutants adsorption such as aspirin, paracetamol, ibuprofen, diazepam, diclofenac, and carbamazepine on kaolinite have been performed using DFT calculations. We demonstrated that:

The adsorptions of these components are exothermic.

The adsorption of molecules on the aluminol (001) surface of kaolinite is more favored than on the siloxane surface and occurs preferentially with a flat configuration for most molecules.

The adsorption of water on the kaolinite aluminol surface is favored in its top position and should inhibit only the adsorption of diazepam considering the adsorption energies.

Kaolinite is a good candidate for the depollution of wastewaters since the six most encountered pharmaceutical molecules adsorb spontaneously, i.e. with an exothermic nature, on its (001) surface without risking the formation of dangerous by-products or any water acidification.

Finally, by heating kaolinite to 360 K, it can discharge the six studied pollutants and be reactivated for further uses, which make kaolinite an excellent candidate for the water depollution.

This theoretical study shed light onto the adsorption mechanisms of the six considered molecules and demonstrated that kaolinite can be used for the removal of pharmaceutical pollutant molecules from wastewater. It constitutes an encouraging result since it could improve the efficiency of water treatment facilities by using kaolinite in the depollution process.

Figure 1 .

 1 Figure 1. The 2x2x2 kaolinite supercell generated from the primitive cell and used to create the (001) surfaces, seen from the a Miller index (a) and from the b Miller index (b). Dashed lines represent hydrogen bonds.

Figure 2 .

 2 Figure 2. The two different cells used for this study including the (001) kaolinite surface, which can be (a) the aluminol surface or (b) the siloxane surface, and a vacuum of 20 Å, seen from the b Miller index.

Figure 3 .

 3 Figure 3. 3D explicit representations of the conformations of the six studied molecules.

3. 1 . 1 1 including

 111 Paracetamol (PAR)On the aluminol surface, PAR adsorbs preferably in a flat configuration with ΔEads = -159.4 kJ.mol -1 including ΔEdisp = -91.0 kJ.mol -1 , which represents 57% of the total interaction energy. The vertical adsorption is significantly less favored, with ΔEads = -91.1 kJ.mol -ΔEdisp = -31.1 kJ.mol -1 .

Figure 4 .

 4 Figure 4. Final geometries of paracetamol (PAR) when it is adsorbed on kaolinite (001) aluminol surface in the vertical configuration (a) and in the flat configuration (b) and the electron density iso-surface for the flat adsorption (c). The yellow and blue represented iso-surfaces indicate variations of +0.004 and -0.004 electron/Å - 3 , respectively. Dashed lines represent hydrogen bonds.

  over the vertical adsorption: ΔEads = -154.8 kJ.mol -1 including ΔEdisp = -111.0 kJ.mol -1 (contribution of 71%) for the flat configuration compared to ΔEads = -137.8 kJ.mol -1 including ΔEdisp = -50.3 kJ.mol -1 (contribution of 37%) for the vertical configuration.

Figure 5 .

 5 Figure 5. Final geometries of ibuprofen (IBU) when it is adsorbed on kaolinite (001) aluminol surface in the vertical configuration (a) and in the flat configuration (b) and the electron density change iso-surface for the flat adsorption (c). The yellow and blue represented iso-surfaces indicate variations of +0.004 and -0.004 electron/Å -

Figure 6 .

 6 Figure 6. Final geometries of carbamazepine (CAR) when it is adsorbed on kaolinite (001) aluminol surface in the vertical configuration (a) and in the flat configuration (b) and the electron density change iso-surface for the vertical adsorption (c). The yellow and blue represented iso-surfaces indicate variations of +0.004 and -0.004 electron/Å -3 , respectively. Dashed lines represent hydrogen bonds.

Figure 7 .

 7 Figure 7. Final geometries of aspirin (ASP) when it is adsorbed on kaolinite (001) aluminol surface in the vertical configuration (a) and in the flat configuration (b) and the electron density change iso-surface for the flat adsorption (c). The yellow and blue represented iso-surfaces indicate variations of +0.004 and -0.004 electron/Å -

Figure 8 .

 8 Figure 8. Final geometries of Diclofenac (DIC) when it is adsorbed on kaolinite (001) aluminol surface in the vertical configuration (a) and in the flat configuration (b) and the electron density change iso-surface for the flat adsorption (c). The yellow and blue represented iso-surfaces indicate variations of +0.004 and -0.004 electron/Å - 3 , respectively. Dashed lines represent hydrogen bonds.

Figure 9 .

 9 Figure 9. Final geometries of Diazepam (DIA) when it is adsorbed on kaolinite (001) aluminol surface in the vertical configuration (a) and in the flat configuration (b) and the electron density change iso-surface for the flat adsorption (c). The yellow and blue represented iso-surfaces indicate variations of +0.004 and -0.004 electron/Å -

Figure 10 .

 10 Figure 10. Adsorption energies of water and the six pharmaceutical molecules in their most favored configuration on both aluminol and siloxane surfaces. The blue and green dotted lines represent the water adsorption energy for the aluminol and the siloxane surfaces, respectively.

Figure 11 .

 11 Figure 11. O-H distances in the molecules containing O-H groups before (red circles) and after (blue squares) adsorption.

Figure 12 .

 12 Figure 12. Variation of adsorption free enthalpies of the six studied molecules and water on (001) kaolinite aluminol surface versus the system temperature.

Table 1 .

 1 IUPAC name, chemical formula, code used in the text, and medical utilizations of the six studied molecules.

	Molecule	IUPAC name	Chemical formula	Code Utilizations
	Paracetamol	N-(4-hydroxyphenyl)acetamide	C8H9NO2	PAR Antalgic, anti-pyretic
	Ibuprofen	2-[4-(2-methylpropyl)phenyl]propanoic acid	C13H18O2	IBU	Anti-inflammatory, anti-pyretic, pain killer

Table 2 .

 2 Adsorption energies (in kJ.mol -1 ) of water, aspirin (ASP), paracetamol (PAR), ibuprofen (IBU),

	diazepam (DIA), diclofenac (DIC), and carbamazepine (CAR) on the (001) kaolinite aluminol and siloxane
	surfaces for flat and vertical configurations.
	Molecule	Aluminol surface	Siloxane surface

Table 3 .

 3 Comparison of the adsorption energies and the dispersion contribution for each most favored molecule's

	configuration.
	Molecule	Configuration	ΔEads (kJ mol -1 )	ΔEdisp (kJ mol -1 )	Contribution of Edisp
	Aspirin	Flat	-115.1	-98.2	85%
	Paracetamol	Flat	-159.4	-91.0	57%

, respectively. Dashed lines represent hydrogen bonds.

Acknowledgments

This work received funding from the Scientific Council of University of Abomey-Calavi through the Third Edition of its Competitive Research Fund Program (No 632-2018/UAC/SG/AC/SAF/VR-RU/SPRSP/SA). We also thank Professor Daouda MAMA, Coordinator of the "TEHOSAREC" Project, which aims at the treatment of hospital effluents from university health centers in the department of southern Benin, with natural or modified clays and electrochemical methods. We acknowledge the PMMS (Pôle Messin de Modélisation et de Simulation) and GENCI-TGCC (Grant No. 2020-A0080910433) for providing us the computational resources. MB thanks financial support through the COMETE project (COnception in silico de Matériaux pour l'EnvironnemenT et l'Energie) co-funded by the European Union under the program "FEDER-FSE Lorraine et Massif des Vosges 2014-2020".

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.