OAR@UM Collection:

Molecular logic gates as fluorescent markers and DNA binding agents

2025-11-25T11:03:29Z

Title: Molecular logic gates as fluorescent markers and DNA binding agents Abstract: N/A Description: Ph.D.(Melit.)

Green chemistry alternatives for an established industrial process of an active pharmaceutical ingredient (API)

2024-04-03T05:53:44Z

Title: Green chemistry alternatives for an established industrial process of an active pharmaceutical ingredient (API) Abstract: In this research, an effort was made to improve the protection of a starting molecule used in the industrial process for the synthesis of an API. Three protecting groups were utilized, 2- (Trimethylsilyl)ethoxymethyl Chloride (SEM-Cl), Di-tert-butyl Dicarbonate (BOC2O), and Pivaloyloxymethyl Chloride (POM-Cl). Trials were conducted with each group, even attempting to optimize the preexisting reactions, however, only the ones for BOC2O gave good results. The optimization attempt for the SEM-Cl protection failed as the catalyst available to us was not strong enough for the reaction, while no optimization was possible for the POM-Cl as the best catalyst was already being used, and no alternative was available. After analyzing all final purified products with 1H-NMR, IR, and GC, it was clear that the optimized BOC2O protections, despite working well, still contained quite some impurities. However, in comparison to the trials with the other protecting groups, the modified BOC2O trials were still the best alternatives out of all. Ultimately, the results gathered during this research gave an insight to potential alternatives to the industrial synthesis of this API. Furthermore, findings from this research could also be utilized in the optimization of other industrial processes that make use of similar reactions. Description: B.Sc. (Hons)(Melit.)

When computation meets experiment : a combined approach towards understanding crystalline materials properties

2024-03-12T08:39:56Z

Title: When computation meets experiment : a combined approach towards understanding crystalline materials properties Abstract: The solid-state behaviour of an active pharmaceutical ingredient has a significant influence on its function and effectiveness in the body. Due to such importance, a crystallographic study was conducted to analyse and predict such behaviour in three prominent antivirals, namely ganciclovir, famciclovir and valacyclovir (hydrochloride form), all of which act as nucleoside analogue polymerase inhibitors against herpesviruses. This investigation incorporates the complementary use of multiple computational approaches, novel or otherwise, which offer a direct comparison of results and provide a more holistic understanding. A new scoring system for the quantification of molecular flexibility was devised, given the proven lack of appropriateness of the number of rotatable bonds parameter to represent such molecular feature exhaustively. This was followed by conformational analysis, which provided the parameters of the accessible conformational space of each molecule. In addition, this investigation entailed a detailed exploration of each crystalline antiviral, particularly the administered form, from intramolecular and intermolecular levels, including full interaction maps and energy frameworks. This analysis provided an insight of how features at these levels can manifest their impacts on supramolecular traits, such as the conformational polymorphism between GCV form I and II. The crystallographic behaviour was also characterised through the use of variable temperature powder X-ray diffraction and simultaneous thermal analysis. Both intermolecular analysis and experimental work supported the thermodynamic stability of GCV and FCV form I, with minimal risk of polymorphism, as opposed to VCV⸱HCl. This study displayed how polymorphism is governed by the present degree of stability, which in return is influenced by the HB donors to acceptors ratio, HB coordination number per group and the strength of other non-bonding contacts, beyond HB. Different polymorph and co-crystal formation prediction techniques were validated against parallel experimental work and examined to understand better the extent of their applicability. Results demonstrated how the HB propensity model approach is not adequate to classify the thermodynamic stability of forms whose non-bonding network is heavily composed of non-conventional HB interactions and other contacts beyond HB, as GCV and FCV form I. The prediction of co-crystallisation was conducted through four distinct approaches, which were accompanied by the testing of multiple settings so as to improve the quality of outcomes. These considerations were related to the inputted molecular conformations and the selection of interactions. The ranking based on the excess enthalpy evaluated through the COSMO approach, resulted to be an adequate indicator of the suitability of coformers, especially for FCV co-crystals. The highest overall success rate was associated with the HB energy approach at 74.47%, followed by molecular complementarity (68.97%) and HB propensity model (65.38%) procedures, all of which performed better for GCV trials. Description: Ph.D.(Melit.)

The occurrence and distribution of persistent and emerging organic pollutants in Maltese coastal areas

2024-02-21T14:20:50Z

Title: The occurrence and distribution of persistent and emerging organic pollutants in Maltese coastal areas Abstract: The presence of organic contaminants in the marine environment has been a focal point of interest to researchers as they pose a threat to aquatic organisms and human health. In the past, research has often focused on persistent organic pollutants (POPs). This includes legacy contaminants such as several organochlorine pesticides. These are known to be highly resistant to biodegradation and they tend to bio-accumulate in aquatic organisms. However, nowadays research has shifted to include the evaluation of emerging pollutants. This includes chemicals which are not being regulated, and although they may not be persistent by nature, they are constantly being released into the environment. It can be noted that data available on these types of pollutants in the Maltese islands is very limited. Hence, the aim of this study is to investigate the presence of POPs and emerging pollutants in Maltese coastal areas. During this study samples were collected from marine surface waters, during the months of June to August 2021, across the islands of Malta and Gozo. The contaminants present were then extracted using the solid phase extraction technique. A preliminary study, consisting of 10 sampling sites, was first carried out in order to identify the different types of organic pollutants present. This was performed using gas chromatography-mass spectrometry. From this investigation, different types of pollutants were identified including fuel derivatives, personal care products, pharmaceuticals, pesticides, plastic additives and flame retardants. Most of the contaminants were identified as being emerging pollutants rather than legacy contaminants, showing the relevance of these pollutants. For the latter part of this study, a group of emerging pollutants known as phthalate acid esters were investigated across 28 sampling sites. These were quantified using ultraperformance liquid chromatography mass spectrometry. Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) were investigated as these are some of the most common plasticisers used in various plastic products. In fact, both of these contaminants were found in 96% of the locations sampled with concentrations ranging from