1 Water-Soluble Aza-BODIPYs: biocompatible organic dyes for high contrast in vivo NIR-II imaging Amélie Godard a‡ , Ghadir Kalot b‡ , Jacques Pliquett a , Benoit Busser b-c , Xavier Le Guével b , K. David Wegner d , Ute Resch-Genger d , Yoann Rousselin a , Jean-Luc Coll b , Franck Denat a , Ewen Bodio a* , Christine Goze a‡* , Lucie Sancey b‡* . (a) Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302, CNRS, Université Bourgogne Franche-Comté, 21000 Dijon, France. (b) Institute for Advanced Biosciences, UGA INSERM U1209 CNRS UMR5309, 38000 Grenoble, France. (c) Grenoble Alpes University Hospital, 38042 Grenoble, France. (d) BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter-Str. 11, 12489 Berlin, Germany. ESI Part Experimental Part Materials and Methods Reactions were carried out in analytical reagent grade solvents from Carlo Erba under normal atmosphere. Non-stabilized dry solvents were purchased from Carlo Erba and dried using a MB-SPS-800 (MBraun) or PureSolv-MD-5 (Inert®). All other reagents were purchased from Sigma Aldrich™ or ACROS Organics™ and used as received without further purification. Reactions were monitored by thin-layer chromatography and RP-HPLC-MS. Analytical thin- layer chromatography was performed with Merck 60 F254 silica gel (precoated sheets, 0.2 mm thick). Column chromatography was carried out using silica gel (Sigma Aldrich; 40-63 µm 230- 400 mesh 60Å). ( 1 H, 13 C, 11 B, 19 F) were recorded at 300K on Bruker 500 Avance III. Chemical shifts are given relative to TMS ( 1 H, 13 C), BF 3 *Et 2 O ( 11 B), CFCl 3 ( 19 F) and were referenced to the residual solvent signal. High-resolution mass spectra were recorded on a Thermo LTQ Orbitrap XL ESI-MS spectrometer. NMR and Mass-analyses were performed at the “Plateforme d’Analyse Chimique et de Synthèse Moléculaire de l’Université de Bourgogne” (PACSMUB). HPLC-MS analyses were performed on a Thermo-Dionex Ultimate 3000 instrument (pump + autosampler at 20 °C + column oven at 25 °C) equipped with a diode array detector (Thermo- Dionex DAD 3000-RS) and a MSQ Plus single quadrupole mass spectrometer equipped with a Phenomenex Kinetex® column (2.6 µm C18 100 Å, LC Column 50 x 2.1 mm). The employed gradient for analyses is the following: