Zahra Abada

Zahra Abada photo

Project Title: 

Multidisciplinary approaches towards affordable antimalarial drugs

Host Organisation: 

School of Chemistry, University of Nottingham

Short Biography

After a Masters in pharmaceutical science at the faculty of pharmacy of the University of Paris-Sud, I joined the team of the Prof. Bruno Figadère in the field of enantioselective catalysis within a CIFRE - Industrial Training and Research Agreement with the start-up Alpha Chimica. My PhD allowed me to explore two important scientific areas. One was the synthesis of chiral catalysts heme-like for enantioselective oxidation of prochiral carbons or ethylenic bonds. The rigid macrocyclic core of porphyrins represent attractive templates for building asymmetric catalysts as cytochromes P450 mimics. The second was to explore these conjugated molecules as antiparasitic agents thanks to their specific electronic properties. Assays were performed using porphyrin derivatives and precursors as antimalarial, antileishmanial and tripanocidal agents showing very interesting activities, sometimes equal to the current best treatments. This project combines several subjects developed in my PhD: the use of porphyrins as photocatalysts, synthetic organic chemistry and compounds that are active against pests.

During my postdoctoral position at the University of Tours in the team of the Prof. François Tran Van, I was involved in an industrial project which required skills in organometallic and polymer chemistry. During the past 2 years I have gained experience with conjugated molecules and macromolecules with interesting application in a wide range of applications in the field of material science. This has stimulated me to think about different ways to combine life science and environmental protection along with contributing to work on processes used for scientific research to industrial area. I am keen to combine my interest in life science with my knowledge and willingness to use green processes applied to medic chemistry and make it transferable to the industrial sector.

My CASCADE-FELLOWSHIP not only allowed me to use these skills, but it also taught me new things in photochemistry, flow chemistry and spectroscopy that will help me to follow my career plan to combine chemistry and life science. Prof. Martyn Poliakoff and his team have, for over 10 years, conducted excellent research in a wide range of topics linked by the themes of green chemistry spectroscopy and alternative solvents, particularly supercritical fluids. I believe this Fellowship has offered me valuable skills represented by the different topics developed by Prof. Martyn Poliakoff and Prof. Mike George, as well as experience abroad and personal development. Finally, it has been a valuable opportunity for me to experience new research, and compare that experience with what I have had in France.

At the end of my CASCADE-FELLOWS Fellowship, I have gained wide range of skills in various domains. As a short term target (1 year) I intend to go back to France and apply for a research grant in a research lab with within the CNRS. I remain interested in applying in start-up companies as in a long-term plan (5 years) I would like to be involved in a entrepreneurship adventure.

Brief description of research project

Artemisinin is an important natural antimalarial drug and its derivatives are first line treatments for fighting malaria. The photochemical generation of singlet oxygen ('02) is a key step in the semi-synthetic production of artemisinin from dihydroartemisinic acid (DHAA) using a photocatalyst to introduce two oxygen molecules through both singlet and triplet states. The attempts to increase the yield of the photochemical route were unsuccessful as several routes were developed giving a 55-67% plateau yield. One of these processes, developed in Nottingham, involved a green strategy where an ambient temperature reaction in THF/H20 with only dihydroartemisinic acid, oxygen and a photocatalyst giving only pure crystalline of artemisinin.' There were additional developments that appeared between the submissions of this CASCADE-FELLOWSHIP application and the start of the project. These developments indicated that the key focus was to obtaining a better understanding of the mechanism of this reaction. Therefore, the research has developed in two parallel directions: (1) the use of high field continuous flow NMR to obtain high-resolution spectra as the reaction proceeds to its various stages. This has resulted in a considerably improved understanding on the relationship of the different intermediates particularly the keto/enol equilibrium. These experiments are now being written for publication. (2) The use of EPR and spin traps to probe radical pathways in these reactions. The EPR experiments have been complemented with the use of phosphorus-containing spin traps and 31P NMR spectroscopy of the resulting trapped radicals. This work is also in preparation for publication. These experiments have given me extensive experience in flow chemistry and high Pressure reactions. This has enabled me to supervise two PhD students: one working on photo-oxidation with singlet oxygen in supercritical scCO2 and the other on the first continuous reaction for the synthesis of quinoline from bio-derived precursors via the Skraup reaction. The photochemical experiments are continuing while the Skraup results are under review in the journal Green Chemistry; this reaction is also a new application of Niobium phosphate as a solid acid catalyst. I have attended several conferences and workshops. I attended career development workshops in York and various courses at the University of Nottingham and have acted as a Co-Chair in the Postdoc Forum Committee, a role that involves among other activities, organizing a one-day symposium for postdoctoral researchers to present their results. Fortunately, the University has provided an additional 5-month funding so that further experimental work could be carried out, with still time to write up the research as papers for high quality journals.