As first defensive line, monocytes are a pivotal cell population of innate immunity. Monocyte activation can be relevant to a range of immune conditions and responses. Here we present new insights into the activation of monocytes by a series of phosphonic acid‐terminated, phosphorus‐containing dendrimers. Various dendritic or subdendritic structures were synthesized and tested, revealing the basic structural requirements for monocyte activation. We showed that multivalent character and phosphonic acid capping of dendrimers are crucial for monocyte targeting and activation. Confocal videomicroscopy showed that a fluorescein‐tagged dendrimer binds to isolated monocytes and gets internalized within a few seconds. We also found that dendrimers follow the phagolysosomial route during internalization by monocytes. Finally, we performed fluorescence resonance energy transfer (FRET) experiments between a specifically designed fluorescent dendrimer and phycoerythrin‐coupled antibodies. We showed that the typical innate Toll‐like receptor (TLR)‐2 is clearly involved, but not alone, in the sensing of dendrimers by monocytes. In conclusion, phosphorus‐containing dendrimers appear as precisely tunable nanobiotools able to target and activate human innate immunity and thus prove to be good candidates to develop new drugs for immunotherapies.—Poupot, M., Griffe, L., Marchand, P., Maraval, A., Rolland, O., Martinet, L., L'Faqihi‐Olive, F.‐E., Turrin, C.‐O., Caminade, A.‐M., Fournié, J.‐J., Majoral, J.‐P., Poupot, R. Design of phosphorylated dendritic architectures to promote human monocyte activation. FASEB J. 20, 2339–2351 (2006)

A first generation phosphorus-containing dendrimer with twelve terminal benzyl dithiobenzoate functions was designed and subsequently used as a multifunctional agent to derive hybrid star copolymers consisting of a dendritic core surrounded by twelve polystyrene branches by reversible addition-fragmentation chain transfer (RAFT).

An operationally simple and concise synthesis of anilinoethanolamines, as NMDA NR2B receptor antagonist ifenprodil analogues, was developed via a copper-catalyzed amination of the corresponding bromoarene. Coupling was achieved with linear primary alkylamines, α,ω-diamines, hexanolamine and benzophenone imine, as well as with aqueous ammonia, in good yields using CuI and N,N-diethylsalicylamide, 2,4-pentadione or 2-acetylcyclohexanone as catalytic systems. Amination with ethylene diamine was efficient even in the absence of an additive ligand, whereas no reaction occurred with ethanolamine whatever the conditions used. The anilinoethanolamines were evaluated as NR2B receptor antagonists in a functional inhibition assay. Aminoethylanilines displayed inhibition effects close to that of ifenprodil.