THE SYNTHESIS AND CHARACTERISATIONS OF POROUS THIOAMIDE-SULFONATED-MODIFIED POLY (ACRYLONITRILE-CO-DIVINYLBENZENE-80) AS POTENTIAL SORBENT TO CAPTURE POLAR ANALYTES

Pharmaceuticals contain biologically active components that can pollute watercourses as a result of excretion from individuals and the uncontrolled release of residues from chemical plants. Pharmaceutical residues can persist at low concentrations in the environment, and thus may be potentially harmful to aquatic animals and humans. The control and monitoring of such residues are therefore of prime interest by, for example, solid-phase extraction using solid sorbents to purify and preconcentrate the residues prior to their chemical analysis. poly(acrylonitrile- co -divinylbenzene-80) (poly(AN- co- DVB-80)) sorbents were synthesised by varying the comonomer feed ratios under precipitation polymerisation conditions to deliver a family of porous polymer microspheres. Acrylonitrile confers polar character onto the sorbents, and the acrylonitrile-derived nitrile groups can be chemically transformed via polymer-analogous reactions into thioamide and sulphonyl functional groups which make the sorbents even more suitable for the capture of polar analytes, including pharmaceuticals. In the present study, the Fourier transform infrared (FTIR) spectroscopy results confirmed the chemical modification of poly(AN- co -DVB-80) (P33) to form thioamide-modified poly(AN- co -DVB-80) (TP33) and sulphonation thioamide-HSO 3 -modified poly(AN- co -DVB-80) (TP33-HSO 3 ) due to the presence of strong peaks at  1050 cm -1 and  1154.47 cm -1 that were assigned to the stretching vibrations of C=S group and SO 3 H group in TP33 and TP33-HSO 3 , respectively. The Bruneaur-Emmett-Teller (BET) data demonstrated that the specific surface area of P33 had decreased significantly from 565.0 m 2 g -1 (P33) to 330.0 m 2 g -1 (TP33) and 5.9 m 2 g -1 (TP33-HSO 3 ) after the chemical modifications were carried out with thiourea and sulphuric acid, respectively. The scanning electron microscopy (SEM) analysis proved that the morphologies structure of the copolymers was retained after chemical modification and sulphonation.

Pharmaceuticals contain biologically active components that can pollute watercourses as a result of excretion from individuals and the uncontrolled release of residues from chemical plants. Pharmaceutical residues can persist at low concentrations in the environment, and thus may be potentially harmful to aquatic animals and humans. The control and monitoring of such residues are therefore of prime interest by, for example, solid-phase extraction using solid sorbents to purify and preconcentrate the residues prior to their chemical analysis. In the present work, poly(acrylonitrile-co-divinylbenzene-80) (poly(AN-co-DVB-80)) sorbents were synthesised by varying the comonomer feed ratios under precipitation polymerisation conditions to deliver a family of porous polymer microspheres. Acrylonitrile confers polar character onto the sorbents, and the acrylonitrile-derived nitrile groups can be chemically transformed via polymer-analogous reactions into thioamide and sulphonyl functional groups which make the sorbents even more suitable for the capture of polar analytes, including pharmaceuticals. In the present study, the Fourier transform infrared (FTIR) spectroscopy results confirmed the chemical modification of poly(AN-co-DVB-80) (P33) to form thioamide-modified poly(AN-co-DVB-80) (TP33) and sulphonation thioamide-HSO3-modified poly(AN-co-DVB-80) (TP33-HSO3) due to the presence of strong peaks at 1050 cm -1 and 1154.47 cm -1 that were assigned to the stretching vibrations of C=S group and SO3H group in TP33 and TP33-HSO3, respectively. The Bruneaur-Emmett-Teller (BET) data demonstrated that the specific surface area of P33 had decreased significantly from 565.0 m 2 g -1 (P33) to 330.0 m 2 g -1 (TP33) and 5.9 m 2 g -1 (TP33-HSO3) after the chemical modifications were carried out with thiourea and sulphuric acid, respectively. The scanning electron microscopy (SEM) analysis proved that the morphologies structure of the copolymers was retained after chemical modification and sulphonation.

In the name of Allah, the Most Gracious, the Most Merciful
First of all, thanks to Allah S.W.T because giving me an opportunity to complete the thesis making just in time. Although I had to face with a lot of difficulties along to accomplish this task, I still manage to finish it successfully.     In this study, poly(AN-co-DVB-80) (Figure1.1) was formed via precipitation polymerisation. Precipitation polymerisation is a synthesis method that is used to form crosslinked monodisperse polymer microsphere (0.1-1.0 μm range). This method provides advantages to the copolymer, which involves nonincorporation of steric stabiliser or electronic surfactant. Therefore, the surface of the copolymer formed is free from any contaminant from surfactant-derived ionic charges. In addition, the morphologies of the polymer particles can be tuned by adjusting the precipitation polymerisation conditions. The formation of monodisperse particles with a narrow particles size distribution is advantageous for column packing in chromatography.

Figure 1.1: The Synthesis of Poly(AN-co-DVB-80)
In the present study, the monomers used were acrylonitrile (AN) and divinylbenzene (DVB-80). The initiator used was benzoyl peroxide (BPO), and the medium was a mixture of acetonitrile and toluene. The initiator (BPO) was utilized to initiate the polymerisation. The mixture of acetonitrile and toluene served as porogen and medium for precipitation polymerisation. Acrylonitrile (Figure 1.2) is an organic compound with the formula of CH2=CHCN, which is colorless, volatile, flammable, and water-soluble liquid at room temperature. It consists of a vinyl group linked to a nitrile and widely used in industry to produce elastomers, resins and to manufacture carbon fibres for aircraft, defense and aerospace industries.  (Figure 1.3) acts as a crosslinker agent, which helps in maintaining the firmness of the PAN system. For instance, the inclusion of DVB-80 units in the PAN system disrupts the nitrile-nitrile dipolar interaction along with the PAN system and consequently facilitate the access of modification reagents into polymer chains during the chemical modification process. The addition of DVB-80 is also to increase the porosity of PAN-based adsorbent and consequently to make adsorption more efficient. Poly(AN-co-DVB-80) porous particles provide micropore content which has a high specific surface area and thus has more interaction points with the analytes to be adsorbed.

Figure 1.3: Molecular Structure of Divinylbenzene-80 (DVB-80)
The copolymer formed was chemically modified by thiourea (Figure 1.4). Thiourea is a strong hydrogen bond donor, which can form hydrogen bonds with many groups such as carboxyl, nitro and in particular phosphate groups due to its -NH2 and sulphur group that can coordinate with pharmaceuticals to form a complex compound. Thus, the chemically modified copolymer with thiourea is expected to act as an active sorbent to adsorb pharmaceutical residues. It was demonstrated that the adsorption performance of these adsorbents was enhanced to some extent owing to their strong complexation interaction with a polar compound such as pharmaceuticals. In addition, by the presence of thiourea in a copolymer may also increase the selectivity of the copolymer as a sorbent towards the polar compound. The adsorbent that has been modified with thiourea promotes ion exchange interactions with the anionic compounds (analytes). Pharmaceuticals were adsorbed at the active site of the thioamide-modified poly(AN-co-DVB-80) which were at C=S and NH groups. Therefore, thioamide-modified poly(AN-co-DVB-80) is expected to be selective for the adsorption of anionic compounds in pharmaceuticals.
Sulphonation was performed on the modified copolymer to form thioamide-HSO3-modified poly(AN-co-DVB-80) (Figure 1.5). Sulphonated polymer leads to a better ion exchange resin which the polymers having positively and negatively charged functional group that can exchange their mobile ions equal charge with the surrounding medium. In addition, introducing sulphonic acid group into the polymer will transform the polymer into the ionomers. An ionomer is a polymer composed of repeat units of both electrically neutral repeating units and ionized units covalently bonded to the polymer backbone as pendant group moieties. These ionomers have excellent chemical and thermal stability and can absorb large amounts of water. They are often used as ion-selective membranes. Other than that, introducing a sulphonic group into the polymer can improve the hydrophilicity of the polymer. Incorporation of polar groups by sulphonation favors water uptake, thus inducing stronger interactions between the resin and oppositely charged ions in pharmaceuticals. The sulphonic acid group leads to the formation of proton and cation conductivity, which ideal for the membranes like proton exchange membrane fuel cells. A sulphonated polymer is highly used in membranes for fuel cells and electrodialysis, exchange resins and catalysts, surgical instruments and wound healing dressings.
The sulphonation can take place before polymerisation (pre-sulphonation) or via post-sulphonation which gives direct influence on the degree of the sulphonation and properties of the sulfonated copolymer. Most of the postsulphonation processes are conducted in a homogenous way which allows the use of less reactive reagent, like complexes of SO3 with amines or phosphates.   Figure 1.6, 1.7, and 1.8 show the molecular structure of the targeted compounds that are mefenamic acid (MA), salicylic acid (SA) and diclofenac (DCF), respectively. MA is an anthranilic acid derivative and belongs to a nonsteroidal anti-inflammatory drug (NSAID). It is used for the treatment of analgesia. Other than that, it also used as an antirheumatic and antipyretic drug, for the treatment of dental pain, headache, and dysmenorrheal (Naveed and Qamar, 2014). MA has side effects that cause headaches, nervousness, vomiting, diarrhea, hematemesis, and haematuria. SA is a medication that widely used as a removal of the outer layer of the skin such as ringworm, warts, acne, and dandruff. SA causes stomach ache, diarrhea, and headache if excessively consumed. DCF is a NSAID that is used to reduce inflammation, joint stiffness caused by arthritis and as an analgesic reducing pain in a certain condition. DCF causes side effects like chest pain, weakness, coughing up blood, and vomit if excessively consumed. In addition, DCF is also known as a compound that affects organ histology and gene expression in fish at concentrations as low as 1 µg·L -1 .

Targeted Compound in This Study
MA, SA and DCF are some of the pharmaceutical residues that may affect the aquatic environment and water supplement. In

Dispersive Solid Phase Extraction (dSPE) Techniques
In this study, dispersive solid-phase extraction (dSPE) technique was used for the extraction process. dSPE is a sorbent-based technique that is widely applied in sample preparation for both samples clean up or analyte preconcentration. It shows considerable benefits over conventional solid phase extraction (SPE), especially in terms of the simplicity of the procedure. This technique is based on the dispersion of a solid sorbent in liquid samples in the extraction isolation and clean-up of different analytes from complex matrices. DSPE is used in pretreatment technique for the analysis of several compounds, for example, extraction, isolation, clean-up, and preconcentration of residues of veterinary drugs, animal tissue, foodstuff, etc. DSPE has a wide range of applications in several fields because it is considered as a selective, robust, and versatile technique.

Research Problems and Research Approaches
The presence of pharmaceutical manufacturers in Malaysia may lead to the discharge of pharmaceutical waste into water sources. On the other hand, the pharmaceutical waste is also introduced into the water sources by excretion from individuals or patients that have consumed pharmaceutical compounds for medicinal purposes. Pharmaceuticals contain an active ingredient that might cause toxicity and pollutes the water. Pharmaceuticals exist in the long term with low concentration and may harmful to aquatic life and human. Most of the factories in Malaysia are inefficient in the removal of these pollutants since the primary and secondary treatments usually applied were not designed for this purpose. However, since legislation on the discharge of pharmaceuticals is expected to come out soon, it is necessary to find efficient treatments (Coimbra et al., 2018). Thus, many works were dedicated by researcher to enhance the uptake of low concentration of pharmaceuticals in water by designing various adsorbents such as activated carbon, carbon nanotubes (CNTs) and zeolites (Basheer, 2018).
However, the major disadvantages of these adsorbents are due to their low adsorption capacities, relatively weak interactions with ions, and difficulties of separation and regeneration from water. Ion-exchange resins were able to remove ions substantially; however, they had low selectivity and showed a high degree of swelling and poor mechanical stability (Samiey et al., 2014).
To overcome these limitations, porous and highly functionalised poly(AN-co-DVB-80), microspheres particles were prepared in the present work. The DVB-80 monomer acted as a crosslinking agent that helped to maintain the firmness and develop a three-dimensional molecule (and hence develop porosity) in the PAN copolymer system. The efficacy of the adsorption capacity was expected to improve with the development of the porosity of the PAN-based polymeric adsorbent. The porous resin had active functional groups upon its chemical treatment with thiourea (on the nitrile units) to develop a basic anion exchanger of poly(AN-co-DVB-80) matrix. Thioamide was selected to instill three amine groups on each of the cyano group with longer pendant chains. The anion exchangers which carried cationic groups (≡N + , =NH + and -NH2 + ) were expected to attach to the reversely charged counterions by electrostatic interactions. In addition, sulphuric acid was introduced onto the thioamide-modified poly(AN-co-DVB-80) by sulphonation to increase the ion exchange resin and induce stronger interactions with the polar compounds (Patiño et al., 2016).
In the present work, a multi-residue method based on dSPE followed by HPLC analysis was used to determine the detection of the pharmaceutical residues during the extraction.

Objectives of The Study
1. To synthesis porous poly(AN-co-DVB-80) copolymer via precipitation polymerisation. 2. To chemically modify the poly(AN-co-DVB-80) copolymer with thiourea to form thioamide-modified poly(AN-co-DVB-80) and sulphonated with sulphuric acid to form thioamide-HSO3-modified poly(AN-co-DVB-80). 3. To evaluate the performance of chemically-modified poly  to capture pharmaceuticals via dispersive solid-phase extraction (

Project Motivation and Research Novelty
In the present work, the novel thioamide-modified poly(AN-co-DVB-80) and thioamide-HSO3-modified poly(AN-co-DVB-80) were produced and used for the extraction of pharmaceuticals to evaluate the performance of the adsorbents. Thus, the polymeric material that is produced in this work is expected to have a potential for application in environmental clean-up, specifically to extract polar pharmaceuticals.
Preparation of porous and highly functionalised poly(AN-co-DVB-80) by using thiourea and sulphuric acid has not been reported elsewhere. The presence of the primary amines in thioamide groups is expected to form various active cationic groups (≡N + , =NH + and -NH2 + ) for the capture of anionic polar compounds. The presence of sulphur in the thioamide group and OSO2 from sulphonation is expected to form various anionic groups (-SH -, R-S-H -2 , O-SO2 -2 ) for the capture cationic polar compounds. In addition, S groups from the thioamide group can be used to form hydrogen bond and in water and can coordinate with pharmaceutical to form complex form.the sulphonation will enhance the ion exchange of the polymer and promoted better interaction with the pharmaceutical residues.
The combination of porous characteristic and highly functionalised copolymer is expected to produce adsorbent with high capacity and selectivity to extract pharmaceuticals due to the pharmaceuticals' potential to bind through either the S or the amine N atoms in thioamide modified poly(AN-co-DVB-80) and -SO3 in thioamide-HSO3-modified poly(AN-co-DVB-80).