Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Comparative biological evaluation and G-quadruplex interaction studies of two new families of organometallic gold(I) complexes featuring N-heterocyclic carbene and alkynyl ligands

Meier-Menches, Samuel M., Aikman, Brech, Döllerer, Daniel, Klooster, Wim T., Coles, Simon J., Santi, Nicolò ORCID: https://orcid.org/0000-0001-6361-5457, Luk, Louis ORCID: https://orcid.org/0000-0002-7864-6261, Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542 and Bonsignore, Riccardo ORCID: https://orcid.org/0000-0003-2699-4384 2020. Comparative biological evaluation and G-quadruplex interaction studies of two new families of organometallic gold(I) complexes featuring N-heterocyclic carbene and alkynyl ligands. Journal of Inorganic Biochemistry 202 , 110844. 10.1016/j.jinorgbio.2019.110844

[thumbnail of JIB-AuNHCs_revised_2019_09_07_revision3.pdf]
Preview
PDF - Accepted Post-Print Version
Download (742kB) | Preview
[thumbnail of Supplementary_JIB_AuNHCs_2019_09_07-revised3.pdf]
Preview
PDF - Supplemental Material
Download (5MB) | Preview

Abstract

Experimental organometallic gold(I) compounds hold promise for anticancer therapy. This study reports the synthesis of two novel families of gold(I) complexes, including N1-substituted bis-N-heterocyclic carbene (NHC) complexes of general formula [Au(N1-TBM)2]BF4 (N1-TBM = N1-substituted 9-methyltheobromin-8-ylidene) and mixed gold(I) NHC-alkynyl complexes, [Au(N1-TBM)alkynyl]. The compounds were fully characterised for their structure and stability in aqueous environment and in the presence of N-acetyl cysteine by nuclear magnetic resonance (NMR) spectroscopy. The structures of bis(1-ethyl-3,7,9-trimethylxanthin-8-ylidene)gold(I), (4-ethynylpyridine)(1,9-dimethyltheobromine-8-ylidene)gold(I) and of (2,8-Diethyl-10-(4-ethynylphenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-4λ4,5λ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinine)(1,3,7,9-tetramethylxanthin-8-ylidene)gold(I) were also confirmed by X-ray diffraction analysis. The compounds were studied for their properties as DNA G-quadruplex (G4 s) stabilizers by fluorescence resonance energy transfer (FRET) DNA melting. Only the cationic [Au(N1-TBM)2]BF4 family showed moderate G4 stabilization properties with respect to the previously reported benchmark compound [Au(9-methylcaffein-8-ylidene)2]+ (AuTMX2). However, the compounds also showed marked selectivity for binding to G4 structures with respect to duplex DNA in competition experiments. For selected complexes, the interactions with G4 s were also confirmed by circular dichroism (CD) studies. Furthermore, the gold(I) complexes were assessed for their antiproliferative effects in human cancer cells in vitro, displaying moderate activity. Of note, among the mixed gold(I) NHC-alkynyl compounds, one features a fluorescent boron-dipyrromethene (BODIPY) moiety which allowed determining its uptake into the cytoplasm of cancer cells by fluorescence microscopy

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Publisher: Elsevier
ISSN: 0162-0134
Date of First Compliant Deposit: 1 October 2019
Date of Acceptance: 8 September 2019
Last Modified: 29 Mar 2024 01:54
URI: https://orca.cardiff.ac.uk/id/eprint/125827

Citation Data

Cited 28 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics