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Fluorescence labelling of an intracellular biomolecule in native living cells is a powerful strategy to achieve in-depth understanding of the biomolecule's roles and functions. Besides being nontoxic and specific, desirable labelling probes should be highly cell permeable without nonspecific interactions with other cellular components to warrant high signal-to-noise ratio. While it is critical, rational design for such probes is tricky. Here we report the first predictive model for cell permeable background-free probe development through optimized lipophilicity, water solubility and charged van der Waals surface area. The model was developed by utilizing high-throughput screening in combination with cheminformatics. We demonstrate its reliability by developing CO-1 and AzG-1, a cyclooctyne- and azide-containing BODIPY probe, respectively, which specifically label intracellular target organelles and engineered proteins with minimum background. The results provide an efficient strategy for development of background-free probes, referred to as 'tame' probes, and novel tools for live cell intracellular imaging.

Introduction: This article introduces a new family of weighted mixture distributions, referred to as θ-WM. The θ-WM family is generated by combining two distributions weighted by a parameter θ, offering notable flexibility to model a wide range of complex phenomena. A special case study of the θ-weighted mixture distribution of Weibull-Lomax (θ-WMWLx) is included, resulting from the combination of Weibull and Lomax distributions. Methods: The research thoroughly examines the reliability and statistical properties of the θ-WMWLx distribution. Key aspects such as stochastic dominance, survival and hazard functions, mean residual life, and moments are addressed. The maximum likelihood method is used to estimate unknown parameters. Results: The research findings show that the θ-WMWLx distribution provides a superior fit compared to competing distributions. The analyses are validated using three real datasets, demonstrating the effectiveness of the proposed distribution. Discussion: The θ-WMWLx distribution stands out for its ability to model complex phenomena with high precision. Validation with real data confirms that the proposed distribution offers a better fit than existing distributions, highlighting its utility and applicability in various statistical analysis contexts. [ABSTRACT FROM AUTHOR]

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Reactions between 8-RS-BODIPY (R = Me, 1) and alkyl and aryl thiols were readily accomplished in dichloromethane to provide a synthetic pathway to a range of new 8-organothio-BODIPYs in good yield. The new alkyl 8-RS-BODIPYs (R = Et, 2; Pr, 3; Bu, 4; [sup.t]Bu, 5; n-dodecyl, 6) exhibit absorption and emission properties essentially unchanged from those of 1 whereas the arylthio analogs (R = Ph, 7; 2,6-[Me.sub.2][C.sub.6][H.sub.3], 8; p-Me[C.sub.6][H.sub.4], 9; p-MeO[C.sub.6][H.sub.4],10) exhibit no fluorescence with the exception of 7, and then only in hexane. In common with other related 8-substituted BODIPYs, the new 8-alkylthio-BODIPY dyes show decreasing fluorescence intensity as solvent polarity increases. Compounds 2, 3, 7, and 8 were characterized via single-crystal X-ray analysis; the alkyl derivatives 2 and 3 exhibited planar BODIPY cores with co-planar organothio- substituents whereas the aryl derivatives exhibited both BODIPY core deformation and significant twisting about the S-C (8) bond removing co-planarity between the aryl group and the distorted BODIPY core. These deformations coincide with the significantly reduced emission properties. Key words: BODIPY, fluorescence, thiolation, structure. Nous avons effectue sans dificulte les reactions entre le 8-RS-BODIPY (R = Me, 1) et des alkylmercaptans ou des arylmercaptans dans le dichloromethane afin d'offrir une voie de synthese permettant d'acceder a une serie de 8-organothio-BODIPY avec unbon rendement. Les nouveaux derives alkyle 8-RS-BODIPY (R = Et, 2; Pr, 3; Bu, 4; [sup.t]Bu, 5; n-dodecyl, 6) presentent essentiellement les memes proprietes d'absorption et d'emission que celles du compose 1, tandis que dans la serie d'analogues arylthio (R = Ph, 7; 2,6-[Me.sub.2][C.sub.6][H.sub.4], 8; p-Me[C.sub.6][H.sub.4], 9; p-MeO[C.sub.6][H.sub.4],10) seul le compose 7 revele une fluorescence, et ce, seulement dans l'hexane. A l'instar d'autres composes apparentes de type BODIPY substitues en position 8, les nouveaux pigments de formule 8-alkylthio-BODIPY presentent une decroissance de l'intensite de la fluorescence en fonction de l'augmentation de la polarite du solvant. Nous avons caracterise les composes 2,3,7 et 8 par analyse des rayons X sur cristal unique; les derives alkyle 2 et 3 presentaient une conformation planaire du noyau BODIPY et une disposition coplanaire du substituant organothio, tandis que les derives aryle presentaient une deformation du noyau BODIPY et une torsion importante de la liaison S-C(8), se traduisant par une suppression de la coplanarite entre le groupement aryle et le noyau BODIPY deforme. Ces deformations coincident avec la reduction considerable des proprietes d'emission. [Traduit par la Redaction] Mots-cles: BODIPY, fluorescence, thiolation, structure., Introduction Boron dypyrromethene (BODIPY) molecules are of current interest due to such properties as strong photostability, high quantum yield emission, and high extinction coefficients. (1,2,3) These features may be tweaked [...]