Upconversion nanoparticles (UCNPs) are optically active materials with near-infrared excitation and tuneable anti-Stokes emission, typically resulting in visible emission. A route to routine and reliable synthesis of water-dispersible UCNPs for biomedical imaging applications is the polyethyleneimine (PEI)- assisted solvothermal autoclave synthesis; however, the properties of the resulting UCNPs remain understudied. Herein, we report how PEI molecular weight alters properties of core-only, red-emitting, water-dispersible PEI-UCNPs. In terms of brightness, 1.2 kDa PEI-UCNPs exhibited 5 times more intense upconversion luminescence (UCL) than 25 kDa PEI-UCNPs and a 29% longer UCL lifetime (LT) for the red emission band (~640-690 nm, 4 F 9/2 → 4 I 15/2 Er 3+ transition) in DI H2O. Dispersal in D2O increased emission across wavebands, with green emission ( 2 H 11/2 , 4 S 3/2 → 4 I 15/2 Er 3+ transition) increasing by 248 - 365% whereas red emission only increased between 38-64%. From our results, we infer that PEI may quench the UCL via high-energy NH vibrations. We also examined Förster Resonance Energy Transfer (FRET) between PEI-UCNPs and an electrostatically adsorbed fluorescent model dye, AlexaFluor647® (AF647). 25 kDa PEI-UCNPs achieved highest LT-estimated FRET efficiencies of ~11% in H2O and 16% in D2O, respectively. These findings highlight that polymer MW should be considered when optimising UCNP synthesis.

In the search for red-shifted small molecule emitters of circularly polarized light, a helically chiral N,N,O,O-boron chelated dipyrromethene (BODIPY) is described containing a meso-CF3 group, prepared in only two synthetic steps. The incorporation of an electron deficient substituent at the meso-position of a helically chiral BODIPY results in significant (similar to 50 nm) red-shift of both the absorption (615 -> 669 nm) and emission maxima (635 -> 686 nm) in comparison to the parent compound, whilst maintaining a high extinction coefficient (83,000 mol(-1) cm(-1)) and reasonable fluorescence quantum yield (0.30). Enantiomers were resolved by chiral stationary phase HPLC and absolute configuration assigned by the comparison of the experimental and calculated ECD spectra (divided by g(abs)divided by = 3.6 x 10(-3)). A luminescence dissymmetry factor (divided by g(lum)divided by = 2.3 x 10(-3)) is reported, well supported by calculation (divided by g(lum(calc))divided by = 2 x 10(-3)), resulting in an overall CPL brightness (B-CPL = 29 M-1 cm(-1)) that is consummate with similar helically chiral monomeric BODIPYs. This work demonstrates the use electron deficient meso-CF3 groups in the development of red-shifted circularly polarised luminescent small organic molecules (CPL-SOMs), whilst maintaining their key chiroptical properties.

ABSTRACT The twisting of chromophores such as perylene diimides (PDIs) into helical structures affords chiroptical properties from discrete molecules, which are of significant value for chiral sensing, imaging and catalysis. Since most helical PDI derivatives are susceptible to racemisation, chiral induction provides a promising, yet underdeveloped, strategy for generating materials with persistent chiroptical properties. For the first time, we use a mechanically planar chiral rotaxane as a configurationally stable chirality source to induce single‐handed helicity in a molecular chromophore, yielding persistent circular dichroism and circularly polarised luminescence. The large π‐surface of the PDI also enables rotaxane self‐assembly, which is rare among mechanically interlocked molecules. While mechanical bonding is shown to influence the geometry of the resulting PDI dimers, mechanical planar chirality directs their handedness, thereby providing control at both the molecular and supramolecular levels.

A series of novel arylalkynylpyridyl-triazacyclononane sensitized macrocyclic europium(III) complexes (EuL) was prepared, and their circularly polarized luminescence characterized in terms of the spectral profile and dissymmetry factor (glum). The series was engineered based on previously reported isostructural complexes by a controlled introduction of structural modifications at different positions with respect to the coordination environment of the emitting europium(III) center. It was established that only those structural features of the macrocyclic ligand that were proximal to the europium(III) center affected CPL properties. These findings could help shape the development of a new class of purpose-built EuL complexes compatible with CPL-unaffecting complex-stage functionalization to introduce advantageous structural features for applications in life and material sciences.

Circularly polarised luminescence (CPL) spectroscopy is a technique with applications in materials chemistry, bioimaging, probing fundamental chirality, but conventional photo-elastic modulator CPL instruments remain bulky, expensive and slow. We report a compact single-channel CPL (SC-CPL) spectrometer that alternates left-and righthanded emission through a piezo-actuated pair of orthogonally aligned achromatic quarter-wave plates using a rapid CCD detector. This design minimises moving optics and eliminates the need for detector matching and pre-calibration. It can operate in various acquisition modes such as time gated acquisition mode for long-lived CPL emission and a quasi-continuous mode for short-lived CPL emission. Validation against a benchmark PEM-CPL system using a range of CPL emitters reproduced fine CPL resolution with high sensitivity, orders of magnitude faster. This blueprint SC-CPL reported herein paves the way towards the world's first complete compact chiroptical toolbox. This could lead to significant advancements with pivotal scientific and societal impact.

Chiral organic materials show great promise in optoelectronics, sensing and catalysis. Among those, macrocycles are of great interest due to their preorganisation and potential amplification of chiroptical properties. Understanding the effects of different sources of chirality on the resulting chiroptical properties of these molecules is key to unlocking tailored chiral materials. To this end, we have synthesised a family of bis-perylene diimide-based macrocycles containing multiple sources of chirality, specifically point chirality in the linker, helical chirality in the perylene diimide and supramolecular chirality in the macrocyclic dimer. We found a dominant effect from the helical chirality of the perylene diimide on the chiroptical properties, including the induction of chirality in an achiral guest molecule, which opens up new possibilities for hybrid chiroptical materials.

Dynamic quenching of the terbium and europium excited states of chiral 9-coordinate complexes incorporating a tetra-azatriphylene sensitising group is shown by emission and CPL spectroscopy to be both chemoselective and stereoselective for electron rich phenols that include (S)-DOPA, dopamine, homovanillic acid and (S) and (R)-Trolox; the efficiency of dynamic quenching is determined neither by the charge nor the oxidation potential of the quenching species.

We report the preparation of left-handed helical fibers, imaged by scanning electron microscopy, with enhanced circularly polarized luminescence (CPL) signals, by the self-assembly of chiral naphthalimide derivatives bearing chiral urea moieties, which exhibit aggregation-induced emission luminescence (AIE) in mixtures of organic solvents with high water content. The helical fibers are driven by specific molecular interactions, the particular geometry of the core dye, and the inherent chirality of the substituents. Notably, enantiomeric pairs (R,R and S,S) of the NMI derivatives displayed mirror-image circular dichroism (CD) signals but both emitted circularly polarized luminescence (CPL) of the same handedness, attributed to the supramolecular interactions at the aggregated state. Furthermore, these organic left-handed fibers served as chiral templates for the growth of silver nanoparticles. The metallization process was confirmed by elemental analysis using energy-dispersive X-ray spectroscopy (FESEM-EDX). This work highlights a strategy for the rational design of chiral aggregation-induced emission luminogens and their use as scaffolds for the synthesis of metal coverings.

Chiral materials that manipulate circularly polarised light have burgeoning applications across optoelectronics, sensing and information encoding, yet the functionality of organic molecular materials is often limited by their relatively low dissymmetry factors ( g abs/lum < 10 − 2 ), including towards the near infrared ( λ > 700 nm). An effective strategy to amplifying g abs/lum is to optimise the chiral arrangement of chromophores, with single crystals providing intrinsic molecular ordering. Herein, we quantify the circular dichroism and circularly polarised luminescence of single crystals of a chiral L‐valinol bis‐perylene diimide macrocycle by Mueller–Matrix polarimetry and circularly polarised luminescence microscopy, as required for the analysis of such anisotropic materials. Through this, we see that organic crystals are valuable for understanding how supramolecular structure can be used to modify the sign, strength and energy of the chiroptical signal. Indeed, by tuning the macrocycle's π–π stacking interactions, our materials deliver strong chiroptical properties ( g abs/lum > 10 − 2 ), including circularly polarised luminescence into the near infrared ( λ = 780 nm).

The binding behaviour of three dynamically racemic Eu(iii) complexes of heptadentate ligands based on triazacyclononane has been examined by luminescence and CPL spectroscopy. The low water solubility of the europium complexes is shown to be related to their tendency to oligomerise in aqueous media via intermolecular carboxylate ligation. Aqueous solubility is enhanced in the presence of hydrogencarbonate, with which a more stable and water soluble 1 : 1 ternary adduct reversibly forms. In one case, the presence of human serum albumin leads to selective complexation of the Λ isomer, while bovine serum albumin favours binding of the Δ enantiomer, as deduced by signature CPL spectra.

The nature of dynamic quenching of the europium or terbum excited states for both Δ and Λ stereoisomeric cationic complexes by S and R Trolox has been studied by total emission and CPL spectroscopy and with the aid of DFT computations. In parallel, investigations of the stereoselectivity of complex association with the model protein, human serum albumin have been undertaken providing an example where binding to the chiral protein leads to preferred population of a twisted square-antiprismatic conformer for the Δ isomer only. Non-linear Stern-Volmer quenching kinetics were observed and the stereoselective behaviour in Trolox binding was interpreted in terms of an exciplex model, in which the binding constant for exciplex formation, Kex, and the rate constant for exciplex decay, k3, determine overall quenching efficiency. Dynamic quenching was most efficient with R Trolox for the Δ Eu and Tb complexes in three different examples. Ground state DFT calculations revealed that the Δ charge transfer complex with S Trolox was 10 kJ mol-1 lower in energy than with R Trolox in the square antiprismatic conformer. However, the opposite energy order was found for the less stable twisted-square-antiprismatic conformer, suggesting that the origins of observed chiral quenching behaviour are not associated with relative free energies of each exciplex, but with their relative rates of decay.

Life on Earth is predominately based upon a single chirality set, but so-called “mirror life” - speculated life of the opposite chirality, either of artificial or natural origin - presents a low-likelihood, but high severity global biosecurity threat. Such an existential risk necessitates that technologies for surveillance and containment of mirror life are developed as a contingency. In this perspective, we propose a method for screening against mirror life hazards via an optical chirality assay, based upon circularly polarized luminescence (CPL) generated either via achiral fluorophores (via supramolecular chirality effects) or intrinsically chiral molecular probes. When bound to biological molecules, CPL-generating probes enable Enantioselective Differential Chiral Contrast (EDCC) imaging to verify chirality of a biological specimen. We set out why a multi-reporter panel approach – incorporating many CPL generating fluorescent/luminescent complexes – in conjunction with testing on conventional life’s chirality set, would be necessary to avoid false positives, and thereby screen against mirror life with a high degree of confidence. The all-optical approach could be deployed via recently innovated optical technologies, i.e. rapid CPL spectroscopy, CPL EDCC microscopes, and CPL EDCC cameras. We envisage that this CPL-based approach to screening against mirror life could be a useful tool for safeguarding against mirror life biohazards in a complimentary manner to any future legislative controls.

The Zn2+ ion has crucial roles in biology, such that the development of fluorescent probes for real-time monitoring of fluctuations in its concentration remains important. We describe a new class of probe that utilizes ortho-aminothiophenol-N,N,S-triacetate (S-APTRA) as the binding site for the metal ion, recently reported to bind Zn2+ with high selectivity over Ca2+ and Mg2+. The S-APTRA unit has been appended with a rosamine fluorophore by a sequence of formylation, condensation with 3-(dimethylamino)phenol, and oxidation. The resulting conjugate S-APTRA-Rosamine fluoresces only weakly in aqueous solution, but its emission is greatly enhanced by Zn2+, probably due to the suppression of a photoinduced electron transfer (PET) quenching process. The probe binds Zn2+ with a dissociation constant, Kd, of 55.7 ± 1.2 nM, matching well with [Zn2+] in many biological cells, with very high selectivity over Ca2+ and Mg2+, and with attractively low-energy emission in the orange-red region. A proof-of-concept imaging experiment in NIH 3T3 cells reveals that the probe can successfully signal changes in [Zn2+] by confocal fluorescence microscopy. Meanwhile, a tetradentate analogue omitting the S-bonded carboxylate also responds to Zn2+ but the affinity is tempered by a factor of around 103. Sulfoxide derivatives of the two systems show no response.

A novel arylalkynylpyridine-sensitised nine coordinate quasi-C 3 symmetric all carboxylate donor europium(iii) complex (EuL) possessing exceptionally high circularly polarised brightness in both ΔJ = 1 and ΔJ = 2 transitions was prepared and tested in spin-coated solid-state PMMA thin films. The authentication of the circularly polarised luminescence (CPL) layer was successfully performed using CPL photography (CPLP) and enantioselective differential chiral contrast (EDCC) imaging for both transitions simultaneously using appropriate band pass filters. The effect of reflective properties of different thin film substrate materials on the recorded chiral contrast was quantified using the newly introduced CPLP dissymmetry factor (g CPLP) which compared to the average dissymmetry factor values obtained using a photo elastic modulator (PEM) based CPL spectrometer. Circularly polarised brightness (CPB) of ΔJ = 2 (590 mol-1 dm3 cm-1 at 607 nm) was the highest ever reported and that of ΔJ = 1 (307 mol-1 dm3 cm-1 at 596 nm) was third best across other CPL-active materials with reported CPB. This makes EuL the best candidate for next-generation CPL-active multi-tier 'chameleon security inks'.

Two BODIPYs were synthesized with 3,5-thienylenevinylene units bathochromically shifting spectral bands. Effects of attaching via the thiophene's 2-position compared to the 3-position were studied spectroscopically and in cellulo. The 2-position offered more efficient donation into the BODIPY core and red-shifted emission, whereas attachment at the 3-position induced a slight twist in the BODIPY core, lowering the molar extinction coefficient and less efficiently participating in conjugation. The dyes are efficiently excited by single-photon red or two-photon near-infrared light, with promising photophysical characteristics making them suitable for live-cell microscopy. Low energy excitation is important as red light offers lower cytotoxicity and increased tissue penetration. Both compounds reported herein are bright, photostable, and possess competitive two-photon absorption cross sections of 397 GM (1 GM = 10-50 cm4 s photon-1) at 950 nm and 279 GM at 820 nm, respectively. Laser-scanning confocal microscopy with both single-photon and multiphoton excitation showed lipid droplet (LD) accumulation and an optimal dosing protocol of 500 nM for 30 min for both dyes. Incubation with oleic acid, a fatty acid known to cause LD proliferation, confirmed the dyes can be used quantitatively. Additionally, both dyes retain within LDs for at least 24 h with minimal toxicity. These features were used to study the LD response of cells to extracellular glucose; a notable increase was observed upon a change of 17.5 mM to 30 mM glucose (13.6-68.5 mean LDs per cell). Studying LD response to glucose is crucial to further understand diseases such as cancer, Alzheimer's disease, and diabetes, and fluorescent dyes such as those presented in this work could be vital tools to achieve this.

Direct photodynamic therapy (PDT) is a growing research area currently being explored as an alternative treatment for various cancers. Compared to traditional, indirect PDT, which exploits the reaction of oxygen with the photosensitizer (PS) to damage specially targeted cells, direct PDT utilizes the PS itself to disrupt the target cell, meaning no reactive oxygen species (ROS) are generated. The activation of Type IV technologies specifically induces a structural change within the photosensitizer, resulting in the activation of its therapeutic effect. In contrast to traditional invasive surgeries, chemotherapy, or ROS-based methods, direct methods of PDT pose significantly less damaging off-target effects. Here, we propose an exciting extension of our prior reported, near-infrared light-activated, molecular nanomachines (MNMs), previously shown to promote cell-specific necrosis via disruption of cellular membranes. We show that the modification of MNMs with polyethylene glycol (PEG), or triphenol phosphonium (TPP+) containing functional groups, allows for homeostatic crossing of the phospholipid bilayer and localization at the mitochondrial membrane. By subsequent activation of the rotor from within the targeted cells, we present the ability to eliminate cells without triggering necrotic cell death, instead inducing an additional mechanism of programmed cell death (PCD), while maintaining the integrity of the cellular membrane, thus enacting a significantly cleaner, more therapeutically favorable mode of inducing cell death. A significant development is in the use of light-activated molecular machines for cancer treatments, with a single MNM-based technology being able to access both necrotic and non-necrotic modes of cell elimination by simply switching the excitation procedure.

We present a novel luminescent europium( iii ) probe for highly selective ADP detection with minimal ATP interference. It enables unprecedented ADP sensing in physiologically relevant ranges, facilitating in vitro and cellular imaging applications.

Copper complexes have great potential to overcome the disadvantages of platinum-based anticancer agents, owing to their lower systemic toxicity. Copper pyrithione showed early promise as an anticancer candidate, but further studies have not been forthcoming. Herein, we report a series of copper pyrithione derivatives that show between 1 and 2 orders of magnitude higher activity than cisplatin against pancreatic and breast cancer cell lines, along with good selectivity over healthy cells. Reactive oxygen species (ROS) generation is determined to be a likely mode of action. A fluorescent analogue shows localisation in the endoplasmic reticulum of cells, which is highly unusual for metal-based therapeutics and opens up the potential for unique modes of therapeutic action.

Combined luminescence studies and stochastic molecular dynamics simulations have revealed for the first time how cooperative hydrophobic binding and reversible metal ion coordination to protein glutamate residues occurs. A combined experimental and theoretical approach has been used to explain the very different free energies of binding observed between three structurally analogous chiral europium(iii) complexes and common variants of serum albumin. In particular, reversible binding of a carboxylate from a glutamate residue was observed; this residue is found in human serum albumin but not the other variants. The binding free energy is exquisitely sensitive to the europium probe structure and charge, and favours complexation of a right handed stereoisomer in the chiral binding pocket. Each process has been visualised by short movies, revealing probe conformational exchange dynamics and the pathway to the protein binding site, on a sub-microsecond timescale.

The organelle-localized photodynamic therapy (PDT) has become a promising strategy for efficient cancer treatment. The photogeneration of reactive oxygen species in the endoplasmic reticulum (ER) leads to lipid oxidation and causes cell apoptosis or necrosis. However, most of the commercially available ER-localized phototherapeutic agents exhibit dark cytotoxicity related to the presence of heavy atoms. In this contribution, we developed a novel heavy-atom free BODIPY photosensitizer that localizes selectively in the ER with good biocompatibility, small dark cytotoxicity and efficient singlet oxygen generation, causing cellular death in a PDT experiment. The molecular design of the BODIPY PS involves two key elements: (i) replacing of the common BF2 group with the 9-borafluorene which strongly enhances intersystem crossing to the triplet state responsible for photogeneration of singlet oxygen, and (ii) introduction of the pendant coumarin group ensuring ER-localization and serving as light-harvesting antenna for energy transfer to BODIPY core structure. The localization of BODIPY-based PS was confirmed by laser scanning confocal microscopy (LSCM) imaging, and co-staining revealed strong localization within the ER.