Environment-sensitive Emission Research Articles

Luminescence-Monitored Progressive Chemical Pressure Implementation Realized through Successive Y3+ and Mg2+ Doping into Ca10.5(PO4)7:Eu2.

Chemical pressure generated through ion doping into crystal lattices has been proven to be conducive to exploration of new matter, development of novel functionalities, and realization of unprecedented performances. However, studies are focusing on one-time doping, and there is a lack of both advanced investigations for multiple doping and sophisticated strategies to precisely and quantitatively track the gradual functionality evolution along with progressive chemical pressure implementation. Herein, high-valent Y3+ and equal-valent Mg2+ is successively doped to replace multiple Ca sites in Ca10.5(PO4)7:Eu2+. The luminescence evolution of Eu2+ serves as an optical probe, allowing step-by-step and atomic-level tracking of the site occupation of Y3+ and Mg2+, interassociation of Ca sites, and ultimately functionality improvement. The resulting Ca8MgY(PO4)7:Eu2+ displays a record-high relative sensitivity for optical thermometry. Utilization of the environment-sensitive emission of Eu2+ as a luminescent probe has offered a unique approach to monitoring structure-functionality evolution in vivo with atomic precision, which shall also be extended to optimization of other functionalities such as ferroelectricity, conductivity, thermoelectricity, and catalytic activity through precise control over atomic diffusion in other types of substances.

A Concerted Enzymatic and Bioorthogonal Approach for Extra- and Intracellular Activation of Environment-Sensitive Ruthenium(II)-Based Imaging Probes and Photosensitizers.

In this article, we report a novel targeting strategy involving the combination of an enzyme-instructed self-assembly (EISA) moiety and a strained cycloalkyne to generate large accumulation of bioorthogonal sites in cancer cells. These bioorthogonal sites can serve as activation triggers in different regions for transition metal-based probes, which are new ruthenium(II) complexes carrying a tetrazine unit for controllable phosphorescence and singlet oxygen generation. Importantly, the environment-sensitive emission of the complexes can be further enhanced in the hydrophobic regions offered by the large supramolecular assemblies, which is highly advantageous to biological imaging. Additionally, the (photo)cytotoxicity of the large supramolecular assemblies containing the complexes was investigated, and the results illustrate that cellular localization (extracellular and intracellular) imposes a profound impact on the efficiencies of photosensitizers.

Environment-sensitive emission of anionic hydrogen-bonded urea-derivative\u2013acetate-ion complexes and their aggregation-induced emission enhancement

Anions often quench fluorescence (FL). However, strong ionic hydrogen bonding between fluorescent dyes and anion molecules has the potential to control the electronic state of FL dyes, creating new functions via non-covalent interactions. Here, we propose an approach, utilising ionic hydrogen bonding between urea groups and anions, to control the electronic states of fluorophores and develop an aggregation-induced emission enhancement (AIEE) system. The AIEE ionic hydrogen-bonded complex (IHBC) formed between 1,8-diphenylnaphthalene (p-2Urea), with aryl urea groups at the para-positions on the peri-phenyl rings, and acetate ions exhibits high environmental sensitivities in solution phases, and the FL quantum yield (QY) in ion-pair assemblies of the IHBC and tetrabutylammonium cations is more than five times higher than that of the IHBC in solution. Our versatile and simple approach for the design of AIEE dye facilitates the future development of environment-sensitive probes and solid-state emitting materials.

2,2-Dipicolylamino substituted 2-(2′-hydroxybenzofuranyl) benzoxazole (HBBO) derivative: Towards ratiometric sensing of divalent zinc cations

A dual-emissive fluorophore, HBBODipic, exhibiting an Excited-State Intramolecular Proton Transfer (ESIPT) process is described herein. This dye incorporates an aromatic amine group on the benzofuran side which is functionalized by two picolyl moieties, enabling the observation of a dual fluorescence emission in most solvents. This attractive dual emission is related to the modulation of the pKa* by electronic substitution and has already been applied for generating panchromatic white-emission. In this contribution, we extend the applicability of these HBBO-based dual emitters to the ratiometric detection of substrates, taking advantage of the highly environment-sensitive emission profile of the dye, the E*/K* intensity ratio being strongly tunable. The presence of a dipicolylamino Zn2+-sensitive chelate on the HBBO π-conjugated core enables a drastic change in the emission spectra upon addition of increasing equivalents of zinc perchlorate. The E*/K* dual emission slowly shifts to a single K* band, evidencing a decrease of electron density on the benzofuranol site, owing to the chelation of the Zn2+ cation at the dipicolylamino site. The results are rationalized using theoretical calculations.

Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes

Brain butyrylcholinesterase (BChE) is an attractive target for drugs designed for the treatment of Alzheimer’s disease (AD) in its advanced stages. It also potentially represents a biomarker for progression of this disease. Based on the crystal structure of previously described highly potent, reversible, and selective BChE inhibitors, we have developed the fluorescent probes that are selective towards human BChE. The most promising probes also maintain their inhibition of BChE in the low nanomolar range with high selectivity over acetylcholinesterase. Kinetic studies of probes reveal a reversible mixed inhibition mechanism, with binding of these fluorescent probes to both the free and acylated enzyme. Probes show environment-sensitive emission, and additionally, one of them also shows significant enhancement of fluorescence intensity upon binding to the active site of BChE. Finally, the crystal structures of probes in complex with human BChE are reported, which offer an excellent base for further development of this library of compounds.

Miniaturized Measurement of Drug-Polymer Interactions via Viscosity Increase for Polymer Selection in Amorphous Solid Dispersions.

Drug-polymer interactions have a substantial impact on stability and performance of amorphous solid dispersions (ASD) but are difficult to analyze. Whereas there are many screening methods described for polymer selection based for example on glass forming ability, drug-polymer miscibility, supersaturation, or inhibition of recrystallization, the distinct detection of physico-chemical interactions mostly lacks miniaturized techniques. This work presents an interaction screening assessing the relative viscosity increase between highly concentrated polymer solutions with and without the model drug ketoconazole (KTZ). The fluorescent molecular rotor 9-(2-carboxy-2-cyanovinyl)julolidine was added to the solutions in a miniaturized setup in μL-scale. Due to its environment-sensitive emission behavior, the integrated fluorescence intensity can be used as a viscosity dye within this screening approach (FluViSc). Differences in relative viscosity increases through addition of KTZ were proposed to rank polymers regarding KTZ-polymer interactions. Absolute viscosities were measured with a cone-plate rheometer as a complimentary method and supported the results acquired by the FluViSc. Solid-state nuclear magnetic resonance (ss-NMR) relaxation time measurements and Raman spectroscopy were utilized to investigate drug-polymer interactions at a molecular level. Whereas Raman spectroscopy was not suited to reveal KTZ-polymer interactions, ss-NMR relaxation time measurements differentiated between the selected polymeric carriers hydroxypropylmethylcellulose acetate succinate (HPMCAS) and polyvinylpyrrolidone vinyl acetate 60:40 (PVP-VA64). Interactions were detected for HPMCAS/KTZ ASD while there was no hint for interactions between KTZ and PVP-VA64. These results were in correlation with the FluViSc. The findings were correlated with the dissolution performance of ASD and found to be predictive for supersaturation and inhibition of precipitation during dissolution.

Visualization of Parallel G-Quadruplexes in Cells with a Series of New Developed Bis(4-aminobenzylidene)acetone Derivatives.

G-quadruplexes (G4s) are unique four-stranded nucleic acid secondary structures formed by G-rich nucleic acid sequences which are prevalent in gene promoter and telomere regions and deemed to play essential roles in many biological and pathological processes. Although attentions to G4s have been paid for nearly 40 years, G4 selectivity and its topology discrimination in cells is still pending. Small fluorescence molecules are emerging as a versatile tool of interrogation of cellular features in vivo. Herein, a new class of bis(4-aminobenzylidene)acetone derivatives GD1, GD2, and GD3 with excellent environment-sensitive emission properties were developed and used for fluorescent detection of G4s. Among them, compound GD3 owning four methoxy groups presented preferable capability of lighting up parallel G4s with a strong red-emission enhancement. The photophysical property of GD3 was systematically investigated to elucidate the turn-on mechanism of GD3 toward parallel G4 structures, which reveal that the binding-induced polarity change of the microenvironment around GD3 together with the fluorophore conformational confinement affected the molecular intramolecular charge-transfer state and resulted the enhanced emission. G4s staining with GD3 in fixed cells was further applied, demonstrating GD3 a promising probe with the ability to visualize the distribution of G4 structures in biological processes. In general, this study provides a new potential scaffold—bis(4-aminobenzylidene)acetone—for design of G4-selective fluorescence probes.

Exploitation of Environment-Sensitive Luminophores in the Design of Sydnone-Based Bioorthogonal Imaging Reagents.

Although the strain-promoted sydnone-alkyne cycloaddition reaction has been utilized for bioconjugation, its potential applications in bioorthogonal labeling and imaging in live cells have not been explored. This communication reports novel bioorthogonal imaging reagents with environment-sensitive emission properties through the modification of sydnone with cyclometalated iridium(III) polypyridine complexes. These complexes displayed significant emission enhancement and lifetime elongation upon reaction with strained alkyne derivatives, and were utilized to label cyclooctyne-modified proteins and ceramide molecules in live cells. Additionally, the manipulation of the photocytotoxicity of the complexes through the use of a bioorthogonal reagent was demonstrated.

Estimation of Hydrogen Bond Donating Ability and the Dipolarity-Polarizability of Associated Water Molecules at the SDS Micellar Interface Using a Fluorescence Indicator

A new methodology for estimation of solvatochromic properties of micelles has been proposed. Two environment sensitive emission properties of a single indicator molecule have been used for this purpose. The hydrogen bond donating ability ( �) and dipolarity- polarizability (� * ) of associated water molecules at the SDS micellar interface has been estimated. The obtained result has been compared to the literature values. Effect of methodology and choice of indicator molecule has also been discussed.

Applications of luminescent inorganic and organometallic transition metal complexes as biomolecular and cellular probes

The rich photophysical properties of luminescent inorganic and organometallic transition metal complexes, such as their intense, long-lived, and environment-sensitive emission, render them excellent candidates for biological and cellular studies. In this Perspective, we review examples of biological probes derived from luminescent transition metal complexes with a d(6), d(8), or d(10) metal center. The design of luminescent covalent labels and noncovalent probes for protein molecules is discussed. Additionally, the recent applications of these complexes as cellular probes and bioimaging reagents are described. Emphasis is put on the structural features, photophysical behavior, biomolecular interactions, cellular uptake, and intracellular localization properties of luminescent transition metal complexes.

Iridium(iii) complexes as therapeutic and bioimaging reagents for cellular applications

There is an emerging interest in applying inorganic and organometallic transition metal complexes to biomolecular and cellular studies. The cytotoxic effects of these complexes on various cancer and normal cells have been examined. Many of these complexes display intense, long-lived, and environment-sensitive emission, rendering them useful live-cell imaging reagents. Of particular interest are iridium(III) complexes, which possess a diversity of molecular structures with intriguing biological activity and photophysical properties. In this review article, we summarize recent work using iridium(III) complexes as anticancer drugs and cellular imaging reagents. We focus on the cytotoxic activity, cellular uptake efficiency and mechanisms, and intracellular distribution properties of these complexes. Additionally, we describe the applications of luminescent iridium(III) complexes in intracellular sensing for ions and small molecules, gene-delivery, and cancer cell detection.

Development of luminescent iridium(iii) polypyridine complexes as chemical and biological probes

A number of luminescent iridium(III) polypyridine complexes have been designed as molecular sensors owing to their rich photophysical properties such as intense, long-lived and environment-sensitive emission. In particular, many complexes exhibit emissive behavior that can be readily controlled using various Werner-type and cyclometalating ligands. In this Perspective, we review some recent examples of luminescent iridium(III) polypyridine complexes as probes for chemical and biological molecules using different strategies. The targets include proton, cations and anions, small molecules, nucleic acids and protein molecules. There is also a recent interest in luminescent iridium(III) polypyridine complexes as cellular probes and imaging reagents; selected examples in these areas are described.

Utilization of the Highly Environment-Sensitive Emission Properties of Rhenium(I) Amidodipyridoquinoxaline Biotin Complexes in the Development of Biological Probes

We report the synthesis and characterization of luminescent rhenium(I) amidodipyridoquinoxaline biotin complexes [Re(CO)3(dpqa)(L)](PF6) (dpqa = 2-(n-butylamido)dipyrido[3,2-f:2',3'-h]quinoxaline; L = 4-(biotinamidomethyl)pyridine (py-4-CH2-NH-biotin) (1), 3-(N-((2-biotinamido)ethyl)amido)pyridine (py-3-CO-NH-en-NH-biotin) (2), 4-(N-((6-biotinamido)hexanoyl)aminomethyl)pyridine (py-4-CH2-NH-cap-NH-biotin) (3)), and their biotin-free counterpart [Re(CO)3(dpqa)(py)](PF6) (py = pyridine (4)). Upon irradiation, these complexes exhibited intense triplet metal-to-ligand charge-transfer (3MLCT) (dpi(Re) --> pi(dpqa)) emission in fluid solutions at 298 K and in alcohol glass at 77 K. However, the emission became much weaker in aqueous buffer, probably due to the interactions of water molecules with the amide substituent of the dpqa ligand. These properties render the complexes good candidates as luminescent probes for hydrophobic media, such as the substrate-binding sites of proteins. The avidin-binding properties of the new biotin complexes have been studied by 4'-hydroxyazobenzene-2-carboxylic acid (HABA) assays, emission titrations, and competitive association and dissociation assays. Most importantly, the complexes showed a profound increase in emission intensities upon binding to avidin. Additionally, we found that the fluorescence of anthracene was quenched by these rhenium(I) complexes, and the 3MLCT emission of the complexes was also quenched by anthracene. On the basis of these findings, new homogeneous assays for biotin using these complexes, avidin, and anthracene-labeled avidin have been designed.