Novel rhenium and technetium metal complexes of N-centred tripodal phosphine ligands towards SPECT imaging
File(s)
Author(s)
Cooper, Saul
Type
Thesis
Abstract
The design and synthesis of targeted radiopharmaceuticals incorporating the diagnostic technetium-99m radioisotope for use in molecular imaging is an ongoing research endeavour in nuclear medicine. Despite notable successes in the use of diphosphines for the formulation of 99mTc-radiopharmaceuticals in the past, such as [99mTc]-[TcO2(tetrofosmin)2]+ for myocardial perfusion imaging, heterofunctionalised phosphines remain an underexplored class of ligand in the design of new imaging agents based on molecular targeting units.
The work presented in this thesis applies the NP2PhXR class of heterofunctionalised phosphines, which has been shown to exhibit robust and tuneable coordination chemistry with several transition metals, to the coordination chemistry of technetium and its heavier congener rhenium. This class of ligand is readily synthesisable and the third arm of N-centred tripodal unit can be further functionalised to facilitate tridentate coordination to a metal centre or reactivity towards the formation of bioconjugate functional groups.
The coordination chemistry of both the parent ligand (NP3Ph) and a phenol-functionalised variant (NP2PhOHAr) have been applied to the coordination chemistry of the [ReVO]3+ unit to explore a [3+2] mixed-ligand approach towards the formation of novel 99mTc radiopharmaceuticals. In the case of the latter ligand, a wide range of derivatives can be obtained following tridentate coordination of the ligand. Such chemistry has also been extended to [ReV(NPh)]3+ imido units, and the long-lived Tc radioisotope 99Tc.
Further derivatisation of the NP2PhXR scaffold has led to the synthesis of several novel ligands bearing N-heterocyclic donors, which have been shown to coordinate effectively to [ReI(CO)3]+ units. These ligands could provide the basis of novel tridentate bifunctional chelators for application to the [99mTc]-[Tc(CO)3(H2O)3]+ core. The robust bidentate coordination exhibited by NP2PhXR has also provided the basis for the synthesis of a series of [ReI(CO)3]+ complexes based on a [2+1] mixed-ligand strategy. Thermal decarbonylation of [ReI(CO)3]+ complexes bearing NP2PhXR ligands has facilitated the synthesis of a novel class of [2+2] cis-[Re(CO)2]+ complexes bearing diimine co-ligands. These complexes have been shown to exhibit MLCT emission bands in the 580 – 600 nm range.
NP2PhXR ligands have been applied in the synthesis of [ReVO2(NP2PhXR)2]+ complexes, which provide a basis for the extension of such heterofunctionalised phosphines to 99mTc radiochemistry.
The work presented in this thesis applies the NP2PhXR class of heterofunctionalised phosphines, which has been shown to exhibit robust and tuneable coordination chemistry with several transition metals, to the coordination chemistry of technetium and its heavier congener rhenium. This class of ligand is readily synthesisable and the third arm of N-centred tripodal unit can be further functionalised to facilitate tridentate coordination to a metal centre or reactivity towards the formation of bioconjugate functional groups.
The coordination chemistry of both the parent ligand (NP3Ph) and a phenol-functionalised variant (NP2PhOHAr) have been applied to the coordination chemistry of the [ReVO]3+ unit to explore a [3+2] mixed-ligand approach towards the formation of novel 99mTc radiopharmaceuticals. In the case of the latter ligand, a wide range of derivatives can be obtained following tridentate coordination of the ligand. Such chemistry has also been extended to [ReV(NPh)]3+ imido units, and the long-lived Tc radioisotope 99Tc.
Further derivatisation of the NP2PhXR scaffold has led to the synthesis of several novel ligands bearing N-heterocyclic donors, which have been shown to coordinate effectively to [ReI(CO)3]+ units. These ligands could provide the basis of novel tridentate bifunctional chelators for application to the [99mTc]-[Tc(CO)3(H2O)3]+ core. The robust bidentate coordination exhibited by NP2PhXR has also provided the basis for the synthesis of a series of [ReI(CO)3]+ complexes based on a [2+1] mixed-ligand strategy. Thermal decarbonylation of [ReI(CO)3]+ complexes bearing NP2PhXR ligands has facilitated the synthesis of a novel class of [2+2] cis-[Re(CO)2]+ complexes bearing diimine co-ligands. These complexes have been shown to exhibit MLCT emission bands in the 580 – 600 nm range.
NP2PhXR ligands have been applied in the synthesis of [ReVO2(NP2PhXR)2]+ complexes, which provide a basis for the extension of such heterofunctionalised phosphines to 99mTc radiochemistry.
Version
Open Access
Date Issued
2021-05
Date Awarded
2021-10
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Long, Nicholas
Sponsor
Engineering and Physical Sciences Research Council
Grant Number
EP/L015226/1
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)