Development of one pot synthetic reactions towards novel squaramides for application in...

Post summary

Applications are invited from suitably qualified candidates interested in pursuing a PhD in the area of organic and analytical chemistry on a recently funded research project within the PMBRC at WIT. This project will include aspects of organic synthesis, analytical method development and characterisation for the purpose of design, synthesis and evaluation of novel organic catalysts for enantioselective synthetic organic reactions as well as compounds capable of binding and transporting anions across biological membranes. The project will therefore include synthesis of novel target organic catalysts/anion receptors, evaluation of their performance as organocatalysts in pharmaceutically relevant organic reactions as well as anion binding and transport, generating a researcher with a broad set of skills highly relevant to the Pharmaceutical Industry.

Enantioselective organocatalysis is defined as the enhancement of chemical reactions using simple, organic, metal-free molecules towards a single enantiomer of synthetic product. It has received increasing attention in recent years in academia and in the pharmaceutical industry due to its benefits over more traditional metal-based catalysts. Organocatalysts possess reduced sensitivity to air and moisture, are more environmentally friendly and are more economically favourable to produce compared to their metal analogues. In addition, the use of enzymes as efficient and green biocatalysts in organic synthesis has 

attracted much attention due to their selectivity, environmental compatibility and ease of recovery. The binding and transport of anions across biological membranes is an important biological process; conditions such as cancer and in particular cystic fibrosis arise due to misregulation of the chloride anion in the human body.

Previously developed research from the PMBRC has generated a novel one-pot synthetic approach to squaramide based compounds and some of these have shown some anion binding and organocatalytic effects to date. This project aims to extend this work to produce the next generation of organocatalyst motifs to further investigate and build on previous results in addition to evaluating new techniques towards enantioselective catalysis and anion binding and transport.

Standard duties and responsibilities of the scholarship

The student will be expected to conduct a combination of literature research and laboratory experimental work and consistently display independent planning and initiative. The research methodology includes:

• Design, synthesis and characterisation of a number of families of novel squaramides (chiral and achiral) containing H-bond donating functionalities.
• Analysis of reaction mixtures and products using techniques such as NMR, MS (GC-MS and LC-MS), IR and HPLC.
• Development of HPLC analytical methods for reaction monitoring and enantioselectivity.
• Reaction mechanism evaluation using Mass Spectrometry.
• Evaluation of these organocatalysts in a chosen synthetic organic reaction, measuring product yield and enantioselectivity and optimising reaction conditions to maximise yield and enantiomeric excess of product.
• Testing the ability of the chosen targets to bind anions using appropriate techniques, evaluate binding stoichiometry and assess transmembrane anion transport using appropriate materials
• Complete and write literature review, reports, posters and PhD thesis outlining the research completed and analysing in full the results obtained.

The student will gain experience in several complementary disciplines, including organic chemistry, analytical chemistry and biology. The student will work within the PMBRC, with a wide range of equipment and expertise available. The student will also collaborate with other members of this group with ongoing related projects and present their work at group team meetings. The project will allow attendance at an international conference for result dissemination and networking. The student will also be required to prepare and submit research papers to high impact international journals as directed by and under the supervision of the Principal Investigator and gain experience in teaching to undergraduates also.