Lipophilic and cationic gallium-68 complexes for the detection of mitochondrial dysfunction

This thesis gives an account of the synthesis of macrocyclic and acyclic ligands for radiolabelling with gallium-68 to afford lipophilic and cationic radiotracers to report on mitochondrial dysfunction. These radiotracers are designed to be lipophilic enough to ensure the successful permeation of lipid bilayer membranes, and to also possess a cationic charge in order to be attracted into the mitochondria in a manner dependent on the mitochondrial membrane potential. The synthesis of novel macrocyclic chelators for gallium-68 labelling is described in chapter 2. The synthesis of three sets of macrocyclic compounds are discussed, beginning with a focus on triarylphosphonium functionalisation to afford lipophilic and cationic compounds. All three sets of compounds described in chapter 2 were successfully radiolabelled with generator-produced gallium-68. Chapter 3 describes this radiolabelling, starting with the optimisation of radiochemical yields through a series of altering reaction condition experiments. Initial screening of these radiolabelled compounds was performed through the measurement of their log D values. RadioHPLC analysis was used to investigate the purity of the reaction mixture and assess the presence of speciation. Chapter 4 described the candidate radiotracer’s behaviour in a preclinical model. The cardiac uptake and retention of the candidate radiotracer was determined using the ex vivo Langendorff isolated perfused heart model in both healthy and depolarised mitochondria, with MIBI used as a baseline for this model. This work provides the foundation for additional, more thorough, biological evaluation of such radiotracers, as well as informing on the design and development of future lipophilic and cationic gallium-68 radiotracers. As well as macrocyclic ligands discussed in chapter 2, several acyclic ligand families were also synthesised. These series of acyclic ligands are described in chapter 5, including a focus on bis(salicylaldimine) compounds and some phosphinic acid functionalised analogues, two series of tridentate ligands which have been shown to selectively form 2:1 complexes with metals in the oxidation state of +3, and a final series of bis(semicarbazone) chelates with a focus on triarylphosphonium functionalisation to yield lipophilic and cationic compounds. Chapter 6 summarises the conclusions of this thesis and ideas for future work of this research. Chapter 7 summarises the experimental procedures for the synthetic chemistry and radiochemistry. Chapter 8 contains an Appendix for NMR, MS and DFT data.Open Acces

Take Me Back to the Garden of Love

[Verse 1] Sweet thoughts of first love are filling me,With joy but once we feel;While thoughts of fear are thrilling me,Its joy may prove unreal.Often ‘twould seem love is luring me,To find that you’re untrue;To have, you reassure me,In hope I long for you. [Chorus]Take me back to your Garden of Love, dear,Once again let me bloom in your heart,Take me back to the beautiful spring time,Where sunshine and love never part.To the rose in my heart that is dying,You are just like the dew from above,I need you, I want you, I love you,Take me back to your Garden of Love. [Verse 2] If in your heart you regret me not,Renew each vow to me;Just like a sweet forget-me-not,Once more each word will be.If in your dreams you could understand,Your love’s a fragrant bow’r;Your heart’s my key to wonderland,Come claim this fading flow’r. [Chorus]

Calf Performance Related to Pasture Quality and Supplements

WVU-Extension fact shee

Calves Weaned and Backgrounded on Pasture Respond to Pasture Nutritive Value and Supplements

How forage quality and feed supplementation effect average daily gain of calves backgrounded on pastur

Class C Orphans in GtoPdb v.2023.1

This set contains class C 'orphan' G protein coupled receptors where the endogenous ligand(s) is not known

Class C Orphans (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

This set contains class C 'orphan' G protein coupled receptors where the endogenous ligand(s) is not known

Unfrustrated Qudit Chains and their Ground States

We investigate chains of 'd' dimensional quantum spins (qudits) on a line with generic nearest neighbor interactions without translational invariance. We find the conditions under which these systems are not frustrated, i.e. when the ground states are also the common ground states of all the local terms in the Hamiltonians. The states of a quantum spin chain are naturally represented in the Matrix Product States (MPS) framework. Using imaginary time evolution in the MPS ansatz, we numerically investigate the range of parameters in which we expect the ground states to be highly entangled and find them hard to approximate using our MPS method.Comment: 5 pages, 5 figures. Typos correcte