The chemistry of new fluorescent and amino acid-appended phosphorus-based ligands

This thesis describes the use of the phosphorus analogous Mannich based condensation reaction, a procedure well established within our research group, to synthesise a number of phosphine containing ligands and their associated coordination complexes which may have potential for medicinal applications.

The first research and discussion (R&D) chapter of this thesis (Chapter 2) utilises the well-established route of adding substituents, in this case PPh₂CH_2- groups, through a hydrazide moiety on a naphthalimide substructure, affording PCNCP ligands 2.16 - 2.19 in yields of 76 – 94%. Synthesised phosphine containing naphthalimide ligand’s coordination capabilities were explored utilising late transition metal precursors PtCl₂(cod), PdCl₂(cod), Au(tht)Cl and AgBF₄. Preliminary fluorescence measurements were conducted on two naphthalimide ligands (2.18 and 2.19) and their associated coordination complexes, excluding silver(I) complexes which could not be explored due to solubility issues. Fluorescence was quenched on coordination to platinum(II) and palladium(II); this may allow the phosphine containing naphthalimides synthesised to be used as a “turn-off” sensor for these species.

Chapter 3 explores another class of phosphine containing fluorescent compounds. Naphthalimide fluorophores were substituted for fluorescein (C₂₀H₁₂O₅) and rhodamine (C₂₈H₃₀N₂O₃) derivatives. In a similar approach to Chapter 2, a hydrazide group was introduced to the fluorophore to allow the subsequent monoaddition of a PPh₂CH_2- group, yielding monophosphine (PCN) ligands 3.5 and 3.6. Fluoresceinamine isomer I (C₂₀H₁₃NO₅) was also investigated as a precursor; fluoresceinamine isomer I does not require the addition of the hydrazide functionality since it already possesses an amine moiety which can undergo addition of PPh₂CH_2- groups. This provided access to a bisfunctionalised (PCNCP) fluorescein derivative 3.18 and allowed for exploration of the effect the position of the PPh₂CH_2- groups has on photophysical properties. Phosphine ligands 3.5, 3.6 and 3.18 were coordinated to dichloroplatinu (II), dichloropalladium(II) and chlorogold(I) species and preliminary fluorescence measurements were conducted on all ligands synthesised and their associated coordination complexes.

Similarly to the phosphine functionalised fluorescein ligand (3.5) synthesised, the fluoresceinamine derivative (3.13) fluorescence was quenched on coordination to the metal centres explored. The rhodamine derivative (3.6) preliminarily explored however displayed an additional UV absorption and fluorescence emission band when coordinated to Pt(II) and Pd(II); this may suggest that the rhodamine ligand synthesised could be used as a sensor for the detection of Pt(II) and Pd(II) species.

The final R&D chapter of this thesis (Chapter 4) is a continuation of work studied both by the Smith group and in the literature; synthesising aminomethylphosphine ligands with amino acid backbones. The work described explores expanding the number of amino acids, natural and unnatural, and dipeptides, with PPh₂CH_2- substituents. Examples of (Ph₂PCH₂)₂NX ligands synthesised include: where X = CH₂CONHCH(CH₃)CO₂H (4.8), NHCO₂CH₂CH₃ (4.11) and CH(CH₂Ph)CO₂CH₃ (4.20). Like Chapter 2 and 3, phosphine moieties were introduced via the phosphorus analogous Mannich based condensation reaction.

The coordination capabilities of synthesised aminomethylphosphine ligands, both novel and known, were investigated using PtCl₂(cod), [Ru(η⁶-p-cymene)Cl₂]₂ and Au(tht)Cl precursors, as well as Group 11 metals [Cu(I), Ag(I), Au(I)] which are widely known to exhibit medicinal properties. All compounds synthesised as part of this thesis were analysed through standard spectroscopic techniques, such as ¹H NMR, ³¹P{¹H} NMR, FTIR, ESI-MS and CHN analysis, with some compounds also studied by single crystal X-ray crystallography. A preliminary study of the antibacterial properties of silver(I) complexes, 4.71 – 4.77, synthesised here as part of Chapter 4 is also included and demonstrates silver(I) complexes synthesised showed antibacterial activity against E. Coli and S. Aureus.