AbstractChelating diphosphine ligands have been prepared for two main applications: cytotoxic
Ru complexes and organopalladium alkylation catalysts. By applying rational design ideas
to the ligand targets, the desired properties of the resulting metal complexes have been
Ruthenium diphosphine complexes derived from [RuCl(DMSO-S)2(cis-tach)]Cl (2.1) have
been synthesised and assessed as cytotoxic agents by physical inorganic measurements, in
vitro assays, and imaging techniques. The structures of the diphosphine ligand backbone
and metallacycle size both have a significant influence on cytotoxicity. Therefore,
diphosphines have been specifically designed to be capable of interacting with DNA by
intercalation. Complexes with flexible aliphatic backbones (2.7-2.8) or planar aromatic
backbones (2.17-2.19) are the most active, and we have demonstrated cytotoxicity may be
the result of multiple mechanisms.
The diphosphine bis((diphenylphosphino)methyl)glycine L3.1 is a versatile amide coupling
partner with a variety of aryl and alkyl amines, producing fluorescent ligand conjugates.
In addition, L3.1 forms a Ru chelate complex [RuCl(cis-tach)(L3.1)]Cl (3.1) which serves as
a Ru precursor to fluorescent complex conjugates by coupling of the carboxylic acid
functional group. The photophysical properties of the resulting diphosphine ligands and
Ru complex conjugates have been assessed, and the methodology has been applied to
other fluorescent, therapeutic agents. The cytotoxicity of a pyrene complex conjugate
[RuCl(cis-tach)(L3.2)]Cl (3.3) has been investigated in collaboration with the University of
York and compared to (cis-tach)Ru complexes 2.17-2.19. Changing from an all-carbon
backbone to a PCNCP backbone does not have a detrimental effect on cytotoxicity and
provides a useful point of derivatisation for metal diphosphine drug conjugates.
A series of primary, secondary, and tertiary 1-pyrenylphosphines L4.1-L4.3 has been
synthesised. The luminescence and air stability properties of these ligands and their
associated (arene)Ru complexes have been investigated and it was found that phosphine
oxidation increases fluorescence quantum yield, whereas Ru coordination dramatically
quenches emission. The resistance to air-oxidation of 1-pyrenylphosphines has been
explored experimentally and by computational studies on the phosphine radical cations.
A series of aminophosphine pincer ligands L5.1-L5.9 have been synthesised and their
derived organopalladium complexes with both symmetric (5,5- and 6,6-) and nonsymmetric (5,6-) metallacycles were prepared. The ligands that form non-symmetric
metallacycles have been shown to have a dramatic impact on the Pd coordination
chemistry. When applied as catalysts in allylic alkylation reactions, the larger 5,6- and 6,6-
metallacycles show superior catalytic activity to the widely studied 5,5-metallacyclic
systems. By optimising the reaction, we have found organopalladium catalysts that
perform allylation of dimethylmalonate with high activity and excellent linear selectivity
under mild conditions.
|Date of Award||11 May 2021|
|Supervisor||Paul G Pringle (Supervisor)|