Study of allene-based ligands for transition metal complexes – synthesis and applications in catalysis and as metallodrugs

Maliszewska, Hanna Katarzyna (2021) Study of allene-based ligands for transition metal complexes – synthesis and applications in catalysis and as metallodrugs. Doctoral thesis, University of East Anglia.

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Abstract

From being regarded as a chemical curiosity the allene functional moiety emerged as one of very useful synthetic tools of modern organic chemistry over the past few decades. Inherent axial chirality of the allene skeleton makes it especially attractive in the context of highly demanded new asymmetric synthesis methods. This doctoral thesis explores the use of the allene group as a backbone in a new ligand scaffold for the synthesis of novel allene-derived transition metal complexes for applications in catalysis and as metallodrugs.

Examples of optically active allene-containing complexes equipped mainly with phosphorus-based donor groups have been developed in the past decade and some of them have been found to act as catalysts in asymmetric transformations. However, the field remains highly underexplored.

This doctoral study presents the development and synthesis of new allene-based ligand candidates as well as the use of reported examples in unprecedented settings. These ligands were used to prepare a range of novel symmetric, non-symmetric, neutral and cationic complexes with Pd, Pt and Au metal centres. Depending on the nature of the metal used, the allene-based ligands could retain their cumulene system in the new organometallic compounds. While in the presence of others, the cyclisation afforded new carbene-type complexes (Figure 1). The new series of organometallic compounds were extensively characterised including techniques such as HR-MS, X-ray diffraction, variable temperature NMR spectroscopy and cyclic voltammetry.

The synthesis of allene-derived metal complexes was followed by the investigation of their catalytic activity and bioactivity. The new compounds performed well as catalysts in Heck reaction, cyclisation of 1,6-enynes or metal-catalysed nucleophilic addition to allenes. Preliminary testing of the antimicrobial properties of new complexes showed their high toxicity towards bacteria and fungi with one hit compound currently being evaluated in in vivo models. The antiproliferative properties against MDA-MB-231 human breast adenocarcinoma cancer cell line was probed, showing cytotoxicity in a low micromolar range for selected compounds. The new allene-derived complexes were also found to interact with non-canonical DNA secondary structures such as i-motif and G-quadruplex, giving a first look at potential mechanism of action of these metallodrug candidates.

Preparation of optically enriched allene-based ligands for the asymmetric version of the project was also briefly explored.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Chemistry
Depositing User: Chris White
Date Deposited: 06 Apr 2022 08:37
Last Modified: 06 Apr 2022 08:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/84493
DOI:

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