title: Trianguleniums as Optical Probes for G-Quadruplexes: A Photophysical, Electrochemical, and Computational Study.
abstract: Nucleic acids can adopt non-duplex topologies, such as G-quadruplexes in vitro. Yet it has been challenging to establish their existence and function in vivo due to a lack of suitable tools. Recently, we identified the triangulenium compound DAOTA-M2 as a unique fluorescence probe for such studies. This probe's emission lifetime is highly dependent on the topology of the DNA it interacts with opening up the possibility of carrying out live-cell imaging studies. Herein, we describe the origin of its fluorescence selectivity for G-quadruplexes. Cyclic voltammetry predicts that the appended morpholino groups can act as intra- molecular photo-induced electron transfer (PET) quenchers. Photophysical studies show that a delicate balance between this effect and inter-molecular PET with nucleobases is key to the overall fluorescence enhancement observed upon nucleic acid binding. We utilised computational modelling to demonstrate a conformational dependence of intra-molecular PET. Finally, we performed orthogonal studies with a triangulenium compound, in which the morpholino groups were removed, and demonstrated that this change inverts triangulenium fluorescence selectivity from G-quadruplex to duplex DNA, thus highlighting the importance of fine tuning the molecular structure not only for target affinity, but also for fluorescence response.
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
authors.forename: Arun
authors.initials: A
authors.lastname: Shivalingam
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
authors.forename: Aurimas
authors.initials: A
authors.lastname: Vyšniauskas
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Albrecht
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK.
authors.forename: Andrew J P
authors.initials: AJ
authors.lastname: White
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK. m.kuimova@imperial.ac.uk.
authors.forename: Marina K
authors.initials: MK
authors.lastname: Kuimova
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London, SW7 2AZ, UK. r.vilar@imperial.ac.uk.
authors.forename: Ramon
authors.identifier: http://orcid.org/0000-0003-2992-199X
authors.initials: R
authors.lastname: Vilar
mesh_terms: D004247:DNA / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D054856:G-Quadruplexes; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D005456:Fluorescent Dyes; D009696:Nucleic Acids; D009841:Oligonucleotides; D004247:DNA
keywords: DNA; nucleic acids; optical probes; quadruplexes; triangulenium