Determination of Surface Physicochemical Parameters of Styrene–Divinylbenzene Copolymer Modified by 5-Fluouracil Using Inverse Gas Chromatography

1. Introduction

Styrene–divinylbenzene (S-DVB) copolymers are widely recognized for their structural stability, tunable porosity, and versatility in industrial and biomedical applications [1-4]. The modification of Styrene–divinylbenzene copolymers with 5-Fluorouracil (5-FU) has garnered significant attention due to its potential applications in drug delivery, biomedical engineering, and catalysis [5,6]. Indeed, the incorporation of 5-FU, a chemotherapeutic agent, into these copolymers introduces functional groups that enhance their surface properties, making them suitable for targeted drug delivery and controlled release systems [7-11]. Several surface properties are involved by the modified copolymers. The modification with 5-FU alters the London dispersive and polar free energies of the copolymer, enhancing its interaction with polar and non-polar molecules. This property is crucial for adsorption and separation processes. While the functional groups such as carbonyl and amine groups through 5-FU modification increase the reactivity of the copolymer surface, enabling further functionalization and improving its compatibility with biological systems [12]. The incorporation of 5-FU also affects the porosity and surface morphology of the copolymer, optimizing it for applications such as controlled drug release and catalysis. Enhanced porosity allows for better drug encapsulation and release profiles [8-11,13]. On the other hand, the enhanced biocompatibility of the modified copolymer makes it suitable for biomedical applications, including implants and localized drug delivery systems [6]. Nevertheless, the modification often improves the thermal stability of the copolymer, ensuring its structural integrity during high-temperature processes [14]. This is particularly important for applications in catalysis and industrial processing [15]. Several studies have shown that the supramolecular structure formed by 5-FU on the copolymer surface contributes to increased sorption activity [16]. This is particularly useful in applications requiring selective adsorption, such as chromatography and purification. Whereas, the shielding effect of fluorine atoms in 5-FU reduces surface polarity, can influence interactions with polar solvents and molecules [16,17]. The modified copolymer also influences the surface charge of the copolymer and the Lewis acid-base characteristics, which enhance its ability to interact with specific molecules [18].

Several studies were devoted to study the modification of S-DVB copolymers by modifiers such as 5-Fluouracil and realized supramolecular structures used in many industrial applications [19-27]. However, there is an incredible lack in knowledge of the surface thermodynamic properties of S-DVB copolymer modified by 5-fluouracil, and especially, in the London dispersive and polar surface properties of these materials.

In two recent papers [28,29], we determined the various surface properties of Styrene–divinylbenzene copolymer modified respectively by melamine and 5-hydroxy-6-methyluracil (HMU) by varying the modifier percentage and the temperature using the powerful inverse gas chromatography (IGC) at infinite dilution [30-67]. Indeed, this IGC technique allowed determining the net retention volume $Vn$ of the various organic solvents adsorbed on the S-DVB modified by melamine [28] and HMU [29] for different percentages. The experimental determination of $Vn$ characteristic of the interaction between the solid materials and n-alkanes and polar organic molecules led to the values of all surface thermodynamic parameters of adsorption [46-49,54,64-67], particularly, the free energy of adsorption $∆G_a^0\left(T\right)$, the London dispersive free energy $∆G_a^d\left(T\right)$, the free polar energy $∆G_a^{sp}\left(T\right)$, the Lewis enthalpic acid K_A and base K_D, and the Lewis entropic acid ${\omega }_A$ and base ${\omega }_D$, the London dispersive surface energy ${\gamma }_s^d\left(T\right)$, the polar (or acid–base) surface energy ${\gamma }_s^p$, and the total surface energy ${\gamma }_s$ of the modified copolymers [28,29]. The results obtained with these two systems are very promising in the field of surface chemistry of the modified copolymers.

We aim in this study to fill the gaps and lack of literature in this area by investigating the surface thermodynamic properties of S-DVB copolymers modified by 5-FU at different concentrations using IGC technique at infinite dilution using our new methodology that proved to be the best suited to the study of the physicochemical properties of solid surfaces [54,64-67]. Indeed, the new proposed methodology has remedied the various errors encountered in the literature over the last fifty years and better characterized the surface properties of solid materials using IGC technique at infinite dilution. A comparison of the new results on S-DVB copolymers modified by 5-FU obtained in this work was carried out with those previously determined by modification of S-DVB by melamine and HMU [28,29].

2. Materials and Methods

2.1. Materials and Technique

In this study, the various model organic solvents and the S-DVB copolymers were identical to those employed in two recent papers [28,29], while the 5-FU modifier was purchased from Vecton, St. Petersburg, Russia, using the same experimental protocol. The experimental measurements of the net retention time and retention volume of the adsorbed organic solvents on the system S-DVB / 5-FU at different percentages were obtained from the Chromos GC-1000 chromatograph (from Chromos, Russia) equipped with a flame ionization detector (FID) used with the same previous procedure [28,29].

2.2. Thermodynamic Methods

2.2.1. Polar Free Energy of Adsorption and Lewis Acid-Base Equations

The experimental determination of the net retention volume of the adsorbed molecules led to the values of the free energy of adsorption at various temperatures using the fundamental thermodynamic equation of inverse gas chromatography:

$$∆G_a^0\left(T\right)=-RTlnVn+C\left(T\right)$$

(1)

where $T$ is the absolute temperature, $R$ the perfect constant gas, and $C\left(T\right)$ a constant parameter of adsorption.

Knowing that $∆G_a^0\left(T\right)$ is divided into two contributions: the first one concerns the London dispersive energy $∆G_a^d\left(T\right)$ obtained from the interaction between the modified copolymer and the non-polar solvents such as the n-alkanes (Equation 2) and the second term represents the free polar energy $∆G_a^p\left(T\right)$ obtained by Hamieh method [66,67]:

$$∆G_a^d\left(T\right)=-{\displaystyle \frac{{\alpha }_{0S} }{ H^6}}\left[{\displaystyle \frac{3\mathcal{N}}{{2\left(4\pi {\epsilon }_0\right)}^2}}{\mathcal{P}}_{SX}\right]$$

(2)

where $\mathcal{N}$ is the Avogadro number, ${\epsilon }_0$ the dielectric constant of vacuum, ${\alpha }_{0S}$the deformation polarizability of the solid material denoted by S, $H$ the separation distance between the organic solvent and the solid surface, and ${\mathcal{P}}_{SX}$an interaction parameter used by Hamieh [66,67] as a chromatographic index (Equation 3):

$${\mathcal{P}}_{SX}={\displaystyle \frac{{\epsilon }_S {\epsilon }_X}{\left({\epsilon }_S+{\epsilon }_X\right)}}{\alpha }_{0X}$$

(3)

where ${\alpha }_{0X}$ is the deformation polarizability of the solvent $X$, and ${\epsilon }_S$ and ${\epsilon }_X$ are respectively the ionization energies of the solid and the solvent

The values of $∆G_a^p\left(polar\right)$ were determined using Equation 4:

$$∆G_a^p\left(T, polar\right)=RTlnVn \left(T, polar\right)-RTlnVn \left(T, X_{n.p.}\right)$$

(4)

where $X_{n.p.}$is the geometric point representing the intersection between the straight n-alkanes line with the perpendicular drawn from the point representing the polar probe.

The variations of $∆G_a^p\left(T\right)$ versus the temperature led to the values of the polar enthalpy $\left(-∆H_a^p\right)$ and entropy $\left(-∆S_a^p\right)$ of adsorption obtained using Equation (5):

$$∆G_a^p\left(T\right)=∆H_a^p-T∆S_a^p$$

(5)

Whereas the Lewis enthalpic (K_A, K_D) and entropic (${\omega }_A$, ${\omega }_D$) acid–base parameters were obtained from Equations (6)::

$$\left\{\begin{array}{c}\left(-∆H^p\right)= K_A\times D{N}^{\text{'}}+K_D\times A{N}^{\text{'}} \\ \left(-∆S_a^p\right)={\omega }_A\times {DN}^{\text{'}}+{\omega }_D\times {AN}^{\text{'}}\end{array}\right.$$

(6)

where $D{N}^{\text{'}}$and $AN\text{'}$are, respectively, the corrected electron donor and acceptor numbers of the polar molecule [64-67].

2.2.2. Surface Energetics of the modified copolymers

The application of the Hamieh thermal model [46,46,57, 64-67] allowed us obtaining the London dispersive surface energy ${\gamma }_s^d\left(T\right)$ of the modified copolymer using Equation 7:

$$RTln{V}_n=2\mathcal{N}a\left(T\right){\left[{\gamma }_l^d\left(T\right){\gamma }_s^d\left(T\right)\right]}^{1/2}+\beta \left(T\right)$$

(7)

where $a\left(T\right)$ is the surface area of solvents given by Hamieh [46] as a function of the temperature, ${\gamma }_l^d\left(T\right)$ the London dispersive component of the surface energy of the solvent, and $\beta \left(T\right)$ a constant depending only on the temperature and the solid material.

If ${\gamma }_s^p$ represents the polar surface energy of the S-DVB copolymer, the total surface energy ${\gamma }_s$ can be then written as:

$${\gamma }_s={\gamma }_s^d+{\gamma }_s^p$$

(8)

The Van Oss et al.’s method [36] applied to the modified copolymers led to the values of the Lewis acid ${\gamma }_s^{+}$, and base ${\gamma }_s^{-}$ surface energies using the $∆G_a^p\left(T\right)$ and the known surface parameters of ethyl acetate and dichloromethane:

$$∆G_a^p\left(T\right)=2\mathcal{N}a\left(T\right)\left(\sqrt{{\gamma }_l^{-}{\gamma }_s^{+}}+\sqrt{{\gamma }_l^{+}{\gamma }_s^{-}}\right)$$

(9)

The values of ${\gamma }_s^p$ can be therefore obtained from Expression (10):

$${\gamma }_s^{AB}={\gamma }_s^{p }=2\sqrt{{\gamma }_s^{+}{\gamma }_s^{-}}$$

(10)

3. Results

3.1. Variations of the Free Energy of Adsorption

By determining the values of $RTln{V}_n\left(T\right)$ of different probes adsorbed on the system S-DVB - 5-FU for various temperatures and 5-FU percentages, the results were plotted in Figure 1. Linear variations of $RTln{V}_n\left(T\right)$ were found (Figure 1) for all solvents and solid materials showing a large difference in the behavior in the values of the free energy of adsorption of the probes and copolymers. Higher energy of interaction was obtained with the modified S-DVB for higher percentage of 5-FU. Figure 1 also showed that the polar solvents exchanged the highest free of adsorption. The highest values of $RTln{V}_n\left(T\right)$ were obtained in the case of i-butanol and i-propanol. These preliminary results indicate the higher possibility to have more free energy of interaction with S-DVB modified by 5-FU. These observations were confirmed in the next section by the determination of free polar energy of adsorption of the various polar solvents adsorbed on the modified copolymer proving the high potentiality of the use of such copolymers in industrial and pharmaceutical applications that need more polar surface groups in the copolymer structure.

3.2. Determination of the London Dispersive Surface Energy

The values of ${\gamma }_s^d\left(T\right)$ of the S-DVB / 5-FU systems were determined using Equation (7) for the various modifier percentages at each temperature and applying the Hamieh thermal model [46,47,54,60,64,65]. A decrease of ${\gamma }_s^d\left(T\right)$ was observed in Figure 2a when the temperature increased. However, the London dispersive surface energy of S-DVB copolymer decreased until a 5-FU percentage of 1% and slightly increased for higher percentage of the 5-FU modifier for T =253.15K and 258.13K. An inversion of the tendency was showed in Figure 2b for T =268.15K and 273.13K, where a sharp increase was seen at these temperatures until 1% of 5-FU and then a slight increase was observed for 5% and 10% 5-FU. While a linear increase was observed at a temperature of 263.15K.

The large difference in the values of ${\gamma }_s^d\left(T\right)$ when the 5-FU percentage can be more visualized by giving in Table 1, the various equations of ${\gamma }_s^d\left(T\right)$ of copolymers with other surface thermodynamic parameters by supposing a global linearity of ${\gamma }_s^d\left(T\right)$ versus the temperature.

Results in Table 1 proved an increase in absolute value of the London dispersive surface entropy ${\epsilon }_s^d$ of copolymer, an increase of the extrapolated dispersive surface energy ${\gamma }_s^d(T=0K)$ at 0K, and a gradual decrease of the maximum temperature $T_{Max}$. These results can be better understood in Table 2.

Table 1 clearly showed the important role of the modifier percentage on the various surface parameters of S-DVB copolymer.

Ou new results were compared to the those obtained by using the Dorris-Gray method [69]. This method used Equation (11) to determine ${\gamma }_s^d$ of a solid material:

$${\gamma }_s^d={\displaystyle \frac{{\left[RTln\left[\frac{V_n\left(C_{n+1}{H}_{2(n+2)}\right)}{V_n\left(C_n{H}_{2(n+1)}\right)}\right]\right]}^2}{4{\mathcal{N}}^2{a}_{-CH2-}^2{\gamma }_{-CH2-}}}$$

(11)

where $C_n{H}_{2(n+1)}$ and $C_n{H}_{2(n+1)}$ are the respective formula of two consecutive n-alkanes, $a_{-CH2-}$the surface area of methylene group equal to 6 Ų, and ${\gamma }_{-CH2-}$ its surface energy.

The results obtained using Equation (11) were given in Table 3.

Table 3 showed that the various surface parameters of the modified copolymers are very different from those obtained by our methodology. The deviation between the two methods results from the wrong hypothesis admitted by Dorris-Gray method supposing that the surface area of methylene group does not depend on the temperature. This hypothesis was proved by the Hamieh thermal to be wrong. Indeed, the Hamieh model took into account the effect of the temperature on the surface area of n-alkanes and polar solvents and consequently on the surface area of the methylene group.

3.3. Polar Free Energy of Adsorption

The values of $\left[-∆G_a^p\left(T\right)\right]$ of the adsorbed polar solvents were given in Table S1 versus the temperature. The evolution of $\left[-∆G_a^p\left(T\right)\right]$ against the temperature was drawn in Figure 3. The straight-lines plotted in Figure 3 led to the values of polar enthalpy ($-∆H_a^p)$ and entropy ($-∆S_a^p)$ of adsorption. The obtained results (Figure 3) proved that the solvents with the highest polarity such as i-butanol and i-propanol gave the highest polar free energy of adsorption whatever the used solid surface and for all temperatures. Whereas the lower polar free energy was obtained in the case of benzene and toluene due to their weaker polarity. Nevertheless, it was shown that when the 5-Fu percentage increased the polar free energy increased too and for all polar solvents (Figure 3).

The effect of the 5-FU percentage on the polar energy of adsorption was shown in Figure 4 for the different adsorbed solvents and at various temperatures.

Different behaviors of the adsorbed polar probes were shown in Figure 4. A global increase of $\left[-∆G_a^p\left(T\right)\right]$ in the case of adsorption of solvents such as benzene, toluene, ethyl acetate, i-propanol, n-butanol, and i-propanol highlighting the strong effect of the modifier on the surface properties of the copolymer. An increase of $\left[-∆G_a^p\left(T\right)\right]$ was observed for ethanol followed by a sharp decrease after 1% 5-FU and stability after 5% 5-FU. Whereas a constant pallier was shown with n-butanol and dichloromethane after 1% 5-FU, while a maximum of $\left[-∆G_a^p\left(T\right)\right]$ was observed in the case of i-butanol, thus proving the important role of the terminal polar group of the adsorbed solvents on the modified S-DVB copolymer.

3.4. Lewis Acid–Base Properties

The values of the polar enthalpy $(-∆H_a^p)$ and entropy $(-∆S_a^p)$ of adsorption for the different copolymers obtained from the variations of $\left[-∆G_a^p\left(T\right)\right]$ of the adsorbed solvents given in Table S1 led deducing the Lewis acid-base parameters such as $K_A$, $K_D$, ${\omega }_A$, and ${\omega }_D$ of the different copolymers. The results were then quantified by drawing in Figure 5 the evolution of $\left({\displaystyle \frac{-∆H_a^p}{{AN}^{\text{'}}}}\right)$ and $\left({\displaystyle \frac{-∆S_a^p}{{AN}^{\text{'}}}}\right)$ as a function of $\left({\displaystyle \frac{{DN}^{\text{'}}}{{AN}^{\text{'}}}}\right)$ by varying the 5-FU percentage.

It was shown in Table 4. The results proved the amphoteric character of the different copolymers. A stronger Lewis acidity than the Lewis basicity was observed in the case of the S-DVB copolymer and for a modifier percentage equal to 1%. However, this tendency was inversed for a 5-FU percentage higher than 3% where the Lewis basicity was shown to be two times higher than their Lewis acidity.

All solid surfaces exhibited an amphoteric character (Table 4) showing higher Lewis acidity reaching $K_A=1.95$, with a decrease of the Lewis basicity force from $K_D=0.283$ for S-DVB copolymer to $K_D=0.177$ in the case 10% 5-FU on the S-DVB copolymer. An increase of the Lewis acidity was observed when the 5-FU percentage increased. The Lewis acidity of the modified copolymer increased 2.48 times with 10% 5-FU, while its basicity decreased 0.63 time relative to the alone copolymer. However, the global acid-base character given by $S_K$ and ${S\text{'}}_K$ strongly increased with the increase of the 5-FU percentage. These important results confer to the S-DVB modified by 5-FU to be an excellent candidate in several pharmaceutical and industrial applications that require more Lewis acid-base character.

The study of the various Lewis acid-base parameters against the 5-FU percentage led to the linear equations presented in Table 5 and plotted in Figure 6. Even if the linear regression coefficients are moderately acceptable, however, the different linear relations in Table 5 and shown in Figure 6 proved the crucial role of the addition of 5-FU in the S-DVB copolymer and the increase of the surface groups in the modified copolymer.

3.5. Polar surface energies

The values of $-∆G_a^p\left(T\right)$ of dichloromethane and ethyl acetate given in Table 6 led to those of the polar acid ${\gamma }_s^{+}\left(T\right)$ and base ${\gamma }_s^{-}\left(T\right)$ surface energies of the modified S-DVB copolymer, and therefore to the values of the polar surface energy ${\gamma }_s^p\left(T\right)$ as well as the total surface energy ${\gamma }_s^{tot.}\left(T\right)$ of the solid surfaces .The variations of the various surface energies were plotted in Figure 7.

The straight-lines representing the evolution of different surface energy parameters plotted in Figure 7 showed large difference depending on the 5-FU percentage, the temperature and the surface energy type. A maximum of the surface energy was obtained for the highest 5-FU percentage (10%). All surface energy parameters presented a decrease versus the temperature.

Our new methodology applied to the various copolymers led to the values of the polar surface energy of the solvents drawn in Figure 8, for the different 5-FU percentages. Results in Figure 8 showed that the polar surface energy of the solvents was the lowest in the case of adsorption on S-DVB copolymer (Dowex L-285), while the highest values were obtained in the case of 10% 5-FU on S-DVB copolymer. The conclusions observed in the section are the same as those obtained in other studies [28,29] carried out with other modifiers.

3.6. Determination of the Average Separation Distance H

Previous results led to the determination of the separation distance $H$ between the solvent and the S-DVB modified by 5-FU at various temperatures. The obtained results given in Figure 9 highlighted a difference in the variations of $H\left(T\right)$ between the different solid surfaces, where a slight decrease was observed for the various 5-FU percentages when the temperature increased, whereas an increase of $H\left(T\right)$ was noticed with S-DVB copolymer

3.7. Comparison with Previous Works and Discussion

The present study was devoted to the determination of the surface properties of the styrene–divinylbenzene copolymer modified by 5-fluouracil at different percentages from 1% to 10%, while the previous studies [28,29] were interested in studying the same copolymer but with other modifiers such as melamine [28] and 5-hydroxy-6-methyluracil [29].

Considering the results of the London dispersive surface energy obtained with 1% of the modifier on S-DVB, it was possible to study the effect of the modifier on ${\gamma }_s^d\left(T\right)$ of the modified copolymer. The different equations of ${\gamma }_s^d\left(T\right)$ were presented in Table 7 and their variations plotted in Figure 10.

Table 7 showed that the surface entropy decreased in absolute value as follows:

1% Melamine/S-DVB > 1% HMU/S-DVB > 1% 5-FU/S-DVB

The extrapolated London dispersive surface energy at 0K decreased from melamine to 5-fluouracil. However, the lowest maximum temperature was obtained with 1% 5-hydroxy-6-methyluracil. Whereas, Figure 10 allowed classifying the ${\gamma }_s^d\left(T\right)$ of the various modifiers in decreasing order as follows:

1% Melamine/S-DVB > 1% 5-FU/S-DVB > 1% HMU/S-DVB

The results in Figure 10 highlighted a highest ${\gamma }_s^d\left(T\right)$ with melamine on S-DVB copolymer was obtained, probably due to the severe modification in the surface groups of S-DVB modified by the supramolecule structure of melamine.

The comparison between the polar free energy of the various polar solvents adsorbed on the different modified copolymers allowed drawing the curves of Figure 11 that clearly showed the lowest values of $-∆G_a^p\left(T\right)$ in the case of S-DVB modified by melamine proving the lowest surface groups present at the surface of the modified copolymer. It was observed in Figure 11 that 5-fluouracil on S-DVB gave the highest polar free energy for most polar organic solvents, except for ethyl acetate and toluene that exhibited the highest $-∆G_a^p\left(T\right)$ with S-DVB modified by 5-hydroxy-6-methyluracil.

In order to better understand the effect of the various modifiers on the Lewis acid-base properties, we gave in Figure 12 the structure of these molecules as well their acid-base character.

The first modifier used in the first work [28] is the melamine that can be considered as a strong Lewis Base. Indeed, each –NH₂ group in his structure has a lone pair on the nitrogen, making them electron-rich (Figure 12a). The nitrogen atoms in the triazine ring also contain lone pairs (though their availability is reduced due to aromatic delocalization). Therefore, melamine can donate lone pairs, especially via its amino groups, to Lewis acids. Melamine is not a Lewis acid because it cannot accept electrons.

The second modifier, the 5-hydroxy-6-methyluracil molecule [29], is a pyrimidine derivative and includes the following key groups: two carbonyl groups (=O) at positions 2 and 4 (like in uracil), a hydroxy group (–OH) at position 5, a methyl group (–CH₃) at position 6 and nitrogen atoms at positions 1 and 3 (part of the ring) (Figure 12b). The carbonyl oxygen atoms (at positions 2 and 4) have lone pairs that can donate electrons and give Lewis base sites. Whereas, the hydroxy group at position 5 also has a lone pair on oxygen and can also act as a Lewis base. While the Ring nitrogen atoms have lone pairs, and depending on tautomeric form and protonation state, they may participate as electron donors. This makes 5-hydroxy-6-methyluracil molecule as Lewis base, because it has multiple Lewis base sites, thanks to its oxygen and nitrogen atoms with lone pairs. On the other hand, the hydrogen atoms on the –OH or ring NH groups can participate in hydrogen bonding, but that's Bronsted acidity, not strictly Lewis acidity. This molecule then lacks empty orbitals or strongly electron-deficient centers and cannot be a Lewis acid.

Finally, the 5-fluorouracil (5-FU) contains base ring (Figure 12c): pyrimidine with six-membered ring with nitrogen atoms (at positions 1 and 3) presenting lone pairs that can interact with acid sites, carbonyl groups (=O) at positions 2 and 4 that can donate electrons, and a fluorine atom at position 5, strongly electronegative, having lone pairs, though less available for bonding due to strong bond to carbon. 5-FU is then a Lewis base, capable of donating electron pairs, especially through its carbonyl oxygens and ring nitrogen atoms.5-FU cannot easily interact as Lewis acid because it does not readily accept electron pairs. In conclusion, the three modifiers can be classified in increasing order of Lewis basicity as follows:

5-Fluorouracil < 5-Hydroxy-6-methyluracil < Melamine

The Lewis acid-base results obtained with the three modifiers are given in Table 8. It can be observed that the S-DVB modified by melamine exhibited the highest Lewis acidity relatively to the other modifiers, followed by the copolymer modified by 5-fluouracil and the lowest Lewis acidity was obtained with the modification by 5-Hydroxy-6-methyluracil. Whereas the highest Lewis basicity was obtained with 5-Hydroxy-6-methyluracil followed respectively by 5-fluouracil and melamine modifiers. These results are in good agreement with the Lewis acid-base character discussed above. Indeed, the highest basicity of melamine after addition to S-DVB copolymer, conferred to the modified copolymer the highest acidity relatively to the two other modifiers. However, the highest basicity of the copolymer modified by 5-hydroxy-6-methyluracil is certainly due to the presence of three oxygen atoms which enhance the Lewis basic character of the modified copolymer.

4. Conclusions

All surface thermodynamic parameters of the styrene–divinylbenzene copolymer modified by 5-fluouracil were determined by varying the modifier percentage (from 1% to 10%) and for various temperatures. The free energy of adsorption of model organic molecules was obtained using the IGC technique at infinite dilution, the Hamieh thermal model, and the new method of the separation of the dispersive and polar components of the polar molecules adsorbed on the modified S-DVB copolymer. The new results proved that the highest energy of adsorption was obtained with the modified S-DVB for the highest percentage of 5-FU, and the highest free energy was obtained with i-butanol and i-propanol. Whereas, the London dispersive surface energy of S-DVB copolymer decreased by adding the modifier 5-FU for a percentage of 1%. The comparison between the Hamieh thermal model and the Dorris-Gray method showed an important deviation between the two methods due to the wrong hypothesis admitted by Dorris-Gray method supposing that the surface area of methylene group does not depend on the temperature. It was also observed that the solvents with the highest polarity such as i-butanol and i-propanol gave the highest polar free energy of adsorption whatever the used solid surface and for all temperatures. Whereas, the lower polar free energy was obtained in the case of benzene and toluene due to their weaker polarity, while the polar free energy increased for all polar solvents when the 5-Fu percentage increased. An amphoteric character of the different copolymers was showed. A higher Lewis acidity of the S-DVB copolymer was observed in the case of a modifier percentage equal to 1%. It was proved that the polar surface energy of the solvents was the lowest in the case of adsorption on alone S-DVB copolymer, while the highest values were obtained in the case of 10% 5-FU on S-DVB copolymer. The comparison between the different modifiers led us classifying their ${\gamma }_s^d\left(T\right)$ in decreasing order as follows:

1% Melamine/S-DVB > 1% 5-FU/S-DVB > 1% HMU/S-DVB

This highlighted a highest ${\gamma }_s^d\left(T\right)$ with melamine on S-DVB copolymer, probably due to the severe modification in the surface groups of S-DVB modified by the supramolecule structure of melamine. Furthermore, the lowest values of $-∆G_a^p\left(T\right)$ was obtained in the case of S-DVB modified by melamine proving the lowest surface groups of the modified copolymer. It was showed that 5-fluouracil on S-DVB gave the highest polar free energy for most polar organic solvents, except for ethyl acetate and toluene that exhibited the highest $-∆G_a^p\left(T\right)$ with S-DVB modified by 5-hydroxy-6-methyluracil. It can be also noticed that the S-DVB modified by melamine exhibited the highest Lewis acidity relatively to the other modifiers, followed by the copolymer modified by 5-fluouracil and the lowest Lewis acidity was obtained with the modification by 5-Hydroxy-6-methyluracil. Whereas the highest Lewis basicity was obtained with 5-Hydroxy-6-methyluracil followed respectively by 5-fluouracil and melamine modifiers.