New Heteroleptic Bis-Phenanthroline Copper(I) Complexes with Dipyridophenazine or Imidazole Fused Phenanthroline Ligands: Spectral, Electrochemical, and Quantum Chemical Studies

Two new sterically challenged diimine ligands <b>L</b>_<b>1</b> (2,9-dimesityl-2-(4′-bromophenyl)imidazo[4,5-<i>f</i>][1,10]phenanthroline) and <b>L</b>_<b>2</b> (3,6-di-<i>n</i>-butyl-11-bromodipyrido[3,2-<i>a</i>:2′,3′-<i>c</i>]phenazine) have been synthesized with the aim to build original heteroleptic copper(I) complexes, following the HETPHEN concept developed by Schmittel and co-workers. The structure of <b>L</b>_<b>1</b> is based on a phen-imidazole molecular core, derivatized by two highly bulky mesityl groups in positions 2 and 9 of the phenanthroline cavity, preventing the formation of a homoleptic species, while <b>L</b>_<b>2</b> is a dppz derivative, bearing <i>n</i>-butyl chains in α positions of the chelating nitrogen atoms. The unambiguous formation of six novel heteroleptic copper(I) complexes based on <b>L</b>_<b>1</b>, <b>L</b>_<b>2</b>, and complementary matching ligands (2,9-R₂-1,10-phenanthroline, with R = H, methyl, <i>n</i>-butyl or mesityl) has been evidenced, and the resulting compounds were fully characterized. The electronic absorption spectra of all complexes fits well with DFT calculations allowing the assignment of the main transitions. The characteristics of the emissive excited state were investigated in different solvents using time-resolved single photon counting and transient absorption spectroscopy. The complexes with ligand <b>L</b>_<b>2</b>, bearing a characteristic dppz moiety, exhibit a very low energy excited-state which mainly leads to fast nonradiative relaxation, whereas the emission lifetime is higher for those containing the bulky ligand <b>L</b>_<b>1</b>. For example, a luminescence quantum yield of about 3 × 10^–4 is obtained with a decay time of about 50 ns for <b>C2</b> ([Cu^I(nBu-phen)(<b>L</b>_<b>1</b>)]⁺) with a weak influence of strong coordinating solvent on the luminescence properties. Overall, the spectral features are those expected for a highly constrained coordination cage. Yet, the complexes are stable in solution, partly due to the beneficial π stacking between mesityl groups and vicinal phenanthroline aromatic rings, as evidenced by the X-ray structure of complex <b>C3</b> ([Cu^I(Mes-phen)(<b>L</b>_<b>2</b>)]⁺). Electrochemistry of the copper(I) complexes revealed reversible anodic behavior, corresponding to a copper(I) to copper(II) transition. The half wave potentials increase with the steric bulk at the level of the copper(I) ion, reaching a value as high as 1 V vs SCE, with the assistance of ligand induced electronic effects. <b>L</b>_<b>1</b> and <b>L</b>_<b>2</b> are further end-capped by a bromo functionality. A Suzuki cross-coupling reaction was directly performed on the complexes, in spite of the handicapping lability of copper(I)–phenanthroline complexes

3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice

We propose here the synthesis and biological evaluation of 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues <b>8</b> and <b>9</b>, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T_H1 or T_H2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation