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Synthesis and evaluation of analogues of HYNIC as bifunctional chelators for technetium

Meszaros, L.K., Dose, A., Biagini, S.C.G., Blower, P.J. (2011) Synthesis and evaluation of analogues of HYNIC as bifunctional chelators for technetium. Dalton Transactions, 40 (23). pp. 6260-6267. ISSN 14779226 (ISSN). (doi:10.1039/c0dt01608j) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Abstract

6-Hydrazinonicotinic acid (HYNIC, 1) is a well-established bifunctional technetium-binding ligand often used to synthesise bioconjugates for radiolabelling with Tc-99m. It is capable of efficient capture of technetium at extremely low concentrations, but the structure of the labelled complexes is heterogeneous and incompletely understood. In particular, it is of interest to determine whether, at the no-carrier-added level, it acts in a chelating or non-chelating mode. Here we report two new isomers of HYNIC: 2-hydrazinonicotinic acid (2-HYNIC, 2), which (like 1) is capable of chelation through the mutually ortho hydrazine and pyridine nitrogens and 4-hydrazinonicotinic acid (4-HYNIC, 3), which is not (due to the para-relationship of the hydrazine and pyridine nitrogens). LC-MS shows that the coordination chemistry of 2 with technetium closely parallels that of conventional 1, and no advantages of one over the other in terms of potential labelling efficiency or isomerism were discernable. Both 1 and 2 formed complexes with the loss of 5 protons from the ligand set, whether the co-ligand was tricine or EDDA. Ligand 3, however, failed to complex technetium except at very high ligand concentration: the marked contrast with 1 and 2 suggests that chelation, rather than nonchelating coordination, is a key feature of technetium coordination by HYNIC. Two further new HYNIC analogues, 2-chloro-6- hydrazinonicotinic acid (2-chloro-HYNIC, 4a) and 2,6-dihydrazinonicotinic acid (diHYNIC, 5) were also synthesised. The coordination chemistry of 4a with technetium was broadly parallel to that of 1 and 2 although it was a less efficient chelator, while 5 also behaved as an efficient chelator of technetium, but its coordination chemistry remains poorly defined and requires further investigation before it can sensibly be adopted for 99mTc-labelling. The new analogues 4a and 5 present an opportunity to develop trifunctional HYNIC analogues for more complex bioconjugate synthesis. © 2011 The Royal Society of Chemistry.

Item Type: Article
DOI/Identification number: 10.1039/c0dt01608j
Additional information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] J2 - Dalton Trans. [Field not mapped to EPrints] C2 - 21350776 [Field not mapped to EPrints] AD - King's College London, Division of Imaging Sciences, St Thomas' Hospital, London SE1 7EH, United Kingdom [Field not mapped to EPrints] AD - Functional Materials Group, School of Physical Sciences, University of Kent, Canterbury CT2 7NJ, Kent CT2 7NH, United Kingdom [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled keywords: Bifunctional, Bioconjugates, Coordination chemistry, Key feature, Ligand concentration, Low concentrations, Pyridine nitrogen, Radiolabelling, Biomolecules, Hydrazine, Isomers, Ligands, Pyridine, Stereochemistry, Technetium, Chelation, 6 hydrazinopyridine 3 carboxylic acid, 6-hydrazinopyridine-3-carboxylic acid, chelating agent, coordination compound, drug derivative, EDDA, edetic acid, hydrazine derivative, nicotinic acid derivative, technetium, article, chemistry, high performance liquid chromatography, isomerism, mass spectrometry, synthesis, Chelating Agents, Chromatography, High Pressure Liquid, Coordination Complexes, Edetic Acid, Hydrazines, Isomerism, Mass Spectrometry, Nicotinic Acids, Technetium
Subjects: Q Science > QD Chemistry
R Medicine > R Medicine (General) > R895 Nuclear Medicine
Divisions: Faculties > Sciences > School of Physical Sciences > Functional Materials Group
Depositing User: Giles Tarver
Date Deposited: 21 Jul 2015 10:44 UTC
Last Modified: 29 May 2019 14:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/49610 (The current URI for this page, for reference purposes)
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