Jack D. Fradgley

Bio: Jack D. Fradgley is an academic researcher from Durham University. The author has contributed to research in topics: Europium & Pyridine. The author has an hindex of 4, co-authored 7 publications receiving 27 citations.

The design of responsive luminescent lanthanide probes and sensors.

Abstract: The principles of the design of responsive luminescent probes and sensors based on lanthanide emission are summarised, based on a mechanistic understanding of their mode of action. Competing kinetic pathways for deactivation of the excited states that occur are described, highlighting the need to consider each of the salient quenching processes. Such an analysis dictates the choice of both the ligand and its integral sensitising moiety for the particular application. The key aspects of quenching involving electron transfer and vibrational and electronic energy transfer are highlighted and exemplified. Responsive systems for pH, pM, pX and pO2 and selected biochemical analytes are distinguished, according to the nature of the optical signal observed. Signal changes include both simple and ratiometric intensity measurements, emission lifetime variations and the unique features associated with the observation of circularly polarised luminescence (CPL) for chiral systems. A classification of responsive lanthanide probes is introduced. Examples of the operation of probes for reactive oxygen species, citrate, bicarbonate, α1-AGP and pH are used to illustrate reversible and irreversible transformations of the ligand constitution, as well as the reversible changes to the metal primary and secondary coordination sphere that sensitively perturb the ligand field. Finally, systems that function by modulation of dynamic quenching of the ligand or metal excited states are described, including real time observation of endosomal acidification in living cells, rapid urate analysis in serum, accurate temperature assessment in confined compartments and high throughput screening of drug binding to G-protein coupled receptors.

Synthesis and Evaluation of Europium Complexes that Switch on Luminescence in Lysosomes of Living Cells.

Abstract: A set of four luminescent Eu(III) complexes bearing an extended aryl‐alkynylpyridine chromophore has been studied, showing very different pH‐dependent behaviour in their absorption and emission spectral response. For two complexes with p K a values of 6.45 and 6.20 in protein containing solution, the emission lifetime increases very significantly following protonation. By varying the gate time during signal acquisition, the ‘switch‐on’ intensity ratio could be optimised and enhancement factors of between 250 to 1330 were measured between pH 8 and 4. The best behaved probe showed no dependence on the concentration of common endogenous cations, selected reductants and serum albumin and was examined in live cell imaging studies and used to monitor time‐dependent lysosomal acidification, for which the increase in observed image brightness due to acidification was found to be a factor of 50 in NIH‐3T3 cells.

A family of readily synthesised phosphorescent platinum(II) complexes based on tridentate N^N^O-coordinating Schiff-base ligands

Abstract: The synthesis and photophysical properties of 22 platinum(II) complexes featuring N^N^O-coordinating ligands are described. The complexes have the form Pt(N^N^O-Ln)Cl (n = 1 to 20). The tridentate ligands comprise lateral pyridine and phenolate rings, offering the metal N and O coordination respectively, linked via an imine or hydrazone unit that provides a further, central N atom for coordination. The proligands HLn, some of which have previously been reported for the coordination of 1st row transition metal ions in other contexts, are Schiff bases that are readily synthesised by condensation of salicylaldehydes either with 8-aminoquinoline (to generate imine-based ligands HL1–4) or with 2-hydrazinopyridines (to generate hydrazone-based proligands HL5–20). The Pt(II) complexes are prepared under mild conditions upon treatment of the proligands with simple Pt(II) salts. Metathesis of the chloride ligand by an acetylide is possible, as exemplified by the preparation of two further complexes of the form Pt(N^N^O-Ln)(–CC–Ar), where Ar = 3,5-bis(trifluoromethyl)phenyl. Nine of the complexes have been characterised in the solid state by X-ray diffraction. The imine-based complexes have intense low-energy absorption bands around 520 nm attributed to charge-transfer transitions. They display deep red phosphorescence in solution at ambient temperature, with λmax in the range 635–735 nm, quantum yields up to 4.6% and lifetimes in the microsecond range. The hydrazone complexes that feature a py–NH–NC–Ar linker display pH-dependent absorption spectra owing to the acidity of the hydrazone NH: these complexes have poor photostability in solution. In contrast, their N-methylated analogues (i.e., py–NMe–NC–Ar) show no evidence of photodecomposition. They are phosphorescent in solution at room temperature in the 600–640 nm region, the emission maximum being influenced by substituents in the phenolate ring. The results show how simply prepared tridentate Schiff base ligands – which offer the metal a combination of 5- and 6-membered chelate rings – can provide access to phosphorescent Pt(II) complexes that have superior emissive properties to those of terpyridines, for example.

The design of responsive luminescent lanthanide probes and sensors.

Abstract: The principles of the design of responsive luminescent probes and sensors based on lanthanide emission are summarised, based on a mechanistic understanding of their mode of action. Competing kinetic pathways for deactivation of the excited states that occur are described, highlighting the need to consider each of the salient quenching processes. Such an analysis dictates the choice of both the ligand and its integral sensitising moiety for the particular application. The key aspects of quenching involving electron transfer and vibrational and electronic energy transfer are highlighted and exemplified. Responsive systems for pH, pM, pX and pO2 and selected biochemical analytes are distinguished, according to the nature of the optical signal observed. Signal changes include both simple and ratiometric intensity measurements, emission lifetime variations and the unique features associated with the observation of circularly polarised luminescence (CPL) for chiral systems. A classification of responsive lanthanide probes is introduced. Examples of the operation of probes for reactive oxygen species, citrate, bicarbonate, α1-AGP and pH are used to illustrate reversible and irreversible transformations of the ligand constitution, as well as the reversible changes to the metal primary and secondary coordination sphere that sensitively perturb the ligand field. Finally, systems that function by modulation of dynamic quenching of the ligand or metal excited states are described, including real time observation of endosomal acidification in living cells, rapid urate analysis in serum, accurate temperature assessment in confined compartments and high throughput screening of drug binding to G-protein coupled receptors.

Pyclen-Based Ln(III) Complexes as Highly Luminescent Bioprobes for In Vitro and In Vivo One- and Two-Photon Bioimaging Applications.

Abstract: In addition to the already described ligand L4a, two pyclen-based lanthanide chelators, L4b and L4c, bearing two specific picolinate two-photon antennas (tailor-made for each targeted metal) and one acetate arm arranged in a dissymmetrical manner, have been synthesized, to form a complete family of lanthanide luminescent bioprobes: [EuL4a], [SmL4a], [YbL4b], [TbL4c], and [DyL4c]. Additionally, the symmetrically arranged regioisomer L4a' was also synthesized as well as its [EuL4a'] complex to highlight the astonishing positive impact of the dissymmetrical N-distribution of the functional chelating arms. The investigation clearly shows the high performance of each bioprobe, which, depending on the complexed lanthanide, could be used in various applications. Each presents high brightness, quantum yields, and lifetimes. Staining of the complexes into living human breast cancer cells was observed. In addition, in vivo two-photon microscopy was performed for the first time on a living zebrafish model with [EuL4a]. No apparent toxicity was detected on the growth of the zebrafish, and images of high quality were obtained.

Circularly polarised luminescence laser scanning confocal microscopy to study live cell chiral molecular interactions

Abstract: The molecular machinery of life is founded on chiral building blocks, but no experimental technique is currently available to distinguish or monitor chiral systems in live cell bio-imaging studies. Luminescent chiral molecules encode a unique optical fingerprint within emitted circularly polarized light (CPL) carrying information about the molecular environment, conformation, and binding state. Here, we present a CPL Laser Scanning Confocal Microscope (CPL-LSCM) capable of simultaneous chiroptical contrast based live-cell imaging of endogenous and engineered CPL-active cellular probes. Further, we demonstrate that CPL-active probes can be activated using two-photon excitation, with complete CPL spectrum recovery. The combination of these two milestone results empowers the multidisciplinary imaging community, allowing the study of chiral interactions on a sub-cellular level in a new (chiral) light.

Circularly polarised luminescence laser scanning confocal microscopy to study live cell chiral molecular interactions

Abstract: The molecular machinery of life is founded on chiral building blocks, but no experimental technique is currently available to distinguish or monitor chiral systems in live cell bio-imaging studies. Luminescent chiral molecules encode a unique optical fingerprint within emitted circularly polarized light (CPL) carrying information about the molecular environment, conformation, and binding state. Here, we present a CPL Laser Scanning Confocal Microscope (CPL-LSCM) capable of simultaneous chiroptical contrast based live-cell imaging of endogenous and engineered CPL-active cellular probes. Further, we demonstrate that CPL-active probes can be activated using two-photon excitation, with complete CPL spectrum recovery. The combination of these two milestone results empowers the multidisciplinary imaging community, allowing the study of chiral interactions on a sub-cellular level in a new (chiral) light.

Strong Circularly Polarized Luminescence at 1550 nm from Enantiopure Molecular Erbium Complexes.

Abstract: Circularly polarized luminescence (CPL) in two subregions of the near-infrared (NIR) has been achieved. By leveraging the rigidity and diminishing detrimental vibrations of the heterobimetallic binolate complexes of erbium [(Binol)3ErNa3], species exhibiting an exceptionally high dissymmetry factor (|glum |) of 0.47 at 1550 nm were obtained. These erbium complexes are the first reported examples of CPL observed beyond 1200 nm. Analogous complexes of ytterbium and neodymium also exhibited strong CPL (|glum| = 0.17, 0.05, respectively) in a higher energy NIR window (800-1200 nm). All complexes exhibit high quantum yields (Er: 0.58%, Yb: 17%, Nd: 9.3%) and high BCPL values (Er: 57 M-1 cm-1, Yb: 379 M-1 cm-1, Nd: 29 M-1 cm-1). Because of their strong CPL emission in the telecom band (1550 nm), biologically relevant NIR emission window (800-1100 nm), and synthetic versatility, the complexes reported here could permit further promising developments in quantum communication technologies and biologically relevant sensors.