Water-Soluble Red-Emitting Distyryl-Borondipyrromethene (BODIPY) Dyes for Biolabeling

• Published in: Chemistry : a European journal Vol. 18; no. 23; pp. 7229 - 7242
• Main Authors: Niu, Song-lin, Massif, Cédrik, Ulrich, Gilles, Renard, Pierre-Yves, Romieu, Anthony, Ziessel, Raymond
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.06.2012; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Subjects: Antibodies, Monoclonal - chemistry; biolabeling; BODIPYs; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Carboxylic acids; Chemical Sciences; Chemistry; Chemistry, Multidisciplinary; Coloring Agents; Conjugation; Dyes; Emission; fluorescence; Fluorescent Dyes - chemistry; Molecular Structure; Optical properties; Organic chemistry; Physical Sciences; Saline; Science & Technology; Serum Albumin, Bovine - chemistry; Simulation; Solubility; Styrenes - chemical synthesis; Styrenes - chemistry; sulfonated linker; Water - chemistry; water soluble; Wavelengths; FLUORESCENT LABELS; SOLUBILIZATION; FLUOROPHORES; sulfonated linker; biolabeling; LABELING REAGENTS; SPECTRAL PROPERTIES; BODIPYs; SQUARAINE DYES; SULFO-BETA-ALANINE; RHODAMINE DYES; fluorescence; CYANINE DYES; SUCCINIMIDYL ESTERS; water soluble
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201103613

A series of water‐soluble red‐emitting distyryl‐borondipyrromethene (BODIPY) dyes were designed and synthesized by using three complementary approaches aimed at introducing water‐solubilizing groups on opposite faces of the fluorescent core to reduce or completely suppress self‐aggregation. An additional carboxylic acid functional group was introduced at the pseudo‐meso position of the BODIPY scaffold for conjugation to amine‐containing biomolecules/biopolymers. The optical properties of these dyes were evaluated under simulated physiological conditions (i.e., phosphate‐buffered saline (PBS), pH 7.5) or in pure water. The emission wavelength (λmax) of these labels was found in the 640–660 nm range with quantum yields from modest to unprecedentedly high values (4 to 38 %). The bioconjugation of these distyryl‐BODIPY dyes with bovine serum albumin (BSA) and the monoclonal antibody (mAb) 12A5 was successfully performed under mild aqueous conditions. De nouveaux colorants fluorescents à architecture distyrylborondipyrromethene (BODIPY), émettant dans le rouge et solubles dans l’eau, ont été préparés en utilisant trois méthodes efficaces de fonctionnalisation chimique qui permettent l’introduction de groupements hydrophiles (motifs pseudo‐PEG et sulfonate) sur les parties nord et sud de leur squelette conjugué, et ce afin de réduire ou de supprimer totalement l’agrégation en solution aqueuse. La solubilité dans l’eau des fluorophores ainsi obtenus est élevée et leurs propriétés optiques en milieu physiologique remarquables et comparables à celles déterminées dans les solvants organiques pour les composés hydrophobes parents. De plus, la présence d’une fonction acide carboxylique en position méso de ces composés distyryl‐BODIPY a permis le marquage covalent de protéines d’intérêt (albumine de sérum bovin et anticorps monoclonaux 12A5) via la formation de liens amide dans des conditions biocompatibles. Go bio! Water‐soluble red‐emitting borondipyrromethene (BODIPY) derivatives have been prepared by using mild sulfonation procedures (see figure). The sterically demanding substituents on boron and sulfonate groups on the top/bottom parts of the distyryl‐BODIPY scaffold effectively suppress their aggregation in aqueous solution. These bright fluorophores show promise as biomolecule labels.