https://www.um.edu.mt/library/oar/handle/123456789/77751 Sun, 19 Apr 2026 11:12:53 GMT 2026-04-19T11:12:53Z https://www.um.edu.mt/library/oar/handle/123456789/78608 Title: Physiochemical properties of medicinal compounds in the World Health Organisation's anatomical therapeutic chemical classification Abstract: The Anatomical Therapeutic Chemical (ATC) classification system managed by the World Health Organisation is nowadays considered the most widely used drug classification system. The system encompasses a large number of medicinal products, and studies by Farrugia and Fenech (2014) have investigated the possibility of establishing predictive algorithms for chemical compounds, based on their physiochemical properties, that will anticipate the potential ATC classification of drug candidates. The objective of the study was to extend the studies performed to date by Fenech and Farrugia (2014) to all of the medicinal compounds found in the ATC Classification. Description: M.SC.CHEMISTRY Fri, 01 Jan 2016 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/78608 2016-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/78497 Title: Towards heterogeneous green catalysis for Aza-Michael reactions Abstract: Aza-Michael addition of amines has played an influential role in the pharmaceutical industry because products of such reactions serve as synthetic intermediates for other biologically active molecules. Catalysts implemented for aza-Michael reactions suffer drawbacks, including side-product formation and difficult product extractions, which thus further contribute to the generation of environmentally unfriendly chemical waste. The scope of this research was to find a heterogeneous catalyst that can efficiently promote aza-Michael synthesis under the guidelines of green chemistry. Starting with an assortment of heterogeneous acidic catalysts, each one was tested for double aza-Michael addition. Silica-supported polyphosphoric acid (PPA/SiO) catalyst seemed to be the most promising. Therefore it was introduced to different combinations of reaction temperature, substrates stoichiometry and catalyst loading for the purpose of finding the most optimal conditions. Optimization trials were later repeated for secondary amine mono-addition. Under the determined reaction conditions, PP A/Si07 was found to enhance the versatility of aza-Michael addition by successfully incorporating a structurally diverse collection of amines. Substrate scope was extended to a,B-unsaturated esters, acrylonitrile and 2-propenamide as Michael acceptors to give products in good to excellent yields. All isolated products were successfully characterized using infra-red spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry. The selected catalyst was simple to prepare, stable under long-term storing and easy to separate from the products formed. In addition, PPA/Si02 catalysis did not require drastic reaction conditions such as refluxing temperatures to ensure near stoichiometric yields. Description: M.SC.CHEMISTRY Fri, 01 Jan 2016 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/78497 2016-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/78058 Title: Heterogeneous catalysis in the nitro-mannich reaction Abstract: A simple, efficient, and environmentally friendly method was devised for the nitro Mannich reaction guided by the concept of green chemistry and its twelve principles. A heterogeneous catalyst, Amberlyst A-21-supported copper(!) iodide (Cul.A-21), with a low loading of 5 mol %, was successfully used to catalyse a multicomponent nitro Mannich reaction for the synthesis of P-nitroamines, which are versatile intermediates for the access of valuable bioactive natural products and pharmaceuticals. The Cul.A-21 catalyst was determined to be advantageous in terms of green chemistry due to being relatively cheap, requiring a simple two-step process for preparation, showing high activity since 'it was reusable for at least eight cycles with consistent results and exhibiting high stability, with only 1 % copper leached into solution after eight cycles. Optimisation of the reaction between aldehydes, amines and nitroalkanes at mild reaction conditions, including a solvent-free medium, insensitivity to air or to anhydrous conditions, and an industrially acceptable temperature of 100°C resulted in the synthesis of P-nitroamines, in relatively short times of between 1.5 to 10 h and high yields. Examination of the scope of the reaction, both at room temperature and the optimised 100°C temperature, gave similar results for each product, in terms of isolated yield, despite longer reaction times under the former condition. A wide versatility was observed with 38 products being synthesised, including more than 25 novel P nitroamine products. Reaction times and isolated yields were affected by steric and electronic effects, as well as lone pair availability for the imine nitrogen activation by the bifunctional catalyst. Aromatic aldehydes and amines were highly reactive and resulted in moderate to excellent yields, greater than 90% in some cases. Aliphatic aldehydes were less reactive, furnishing poorer yields whilst aliphatic amines were unreactive. Nitroalkanes, other than nitromethane, resulted in lower yields. The multicomponent reaction was shown to exhibit a green protocol with a 93% atom economy and an E-factor of 1.26. Description: M.SC.CHEMISTRY Fri, 01 Jan 2016 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/78058 2016-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/77769 Title: Method optimisation and robustness testing in HPLC analysis of Angiotensin II receptor blockers (ARB) antagonists Abstract: The active pharmaceutical ingredients irbesartan, losartan and valsmian are three members of a newer class of antihypertensive agents known as angiotensin II receptor blockers. These agents help the blood vessels to dilate, which consequently lowers the blood pressure allowing the hemi to pump blood easier and without extraneous effort. The objective of this dissertation was to optimise an assay and related substances method for each respective active ingredient. The methods optimised were all perf01med in reverse phase chromatography and required an HPLC system coupled with a UV detector as instrnmentation. The optimisation process required gathering information on the physicochemical parameters of the named components first. The second step was to generate an experimental design in a one-variable-at-a-time (OVAT) set up, where certain parameters such as flow rate, column temperature, mobile phase composition, mobile phase buffer pH and HPLC columns were tested and evaluated using statistical tools. Software simulation was used to scout for the best parameters and obtain the finalized method. The third step was to build the optimised method from the results of the OV AT analysis, test it and fine tune accordingly. Once the optimisation goals were met and the final method confirmed, the fourth step was to perform robustness, testing different pre-defined factors at extreme tolerance. Assay method development was performed on irbesartan, losartan and valsartan in reverse phase mode as part of a secondary objective of this study. The developed HPLC method was planned to be transferred geometrically on UHPLC to increase the efficiency and throughput. Therefore, the method development started with pre-selected columns onto which the rest of the method was developed. The data collected from the previous optimisation stage together with various scouting runs led to the development of a robust method. The development strategy and development goals were key for a successful method outcome. Software simulation was also an integral asset especially in the determination of the pH of the mobile phase, where pH 2.0, 3.0 and 4.0 were tested during scouting and the results achieved inputted into the software to generate a resolution map for the whole range of pH values between pH 2.0 and 4.0. In conclusion it was determined that with the knowledge of the physiochemical parameters of the components of interest one can deduce through limited experimentation an optimised method which is effective and robust. Through the same concept, a method was developed and transferred geometrically from HPLC to UHPLC retaining the same component selectivity and specificity. Description: M.SC.CHEMISTRY Fri, 01 Jan 2016 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/77769 2016-01-01T00:00:00Z