Stability and Reactivity of Aromatic Radical Anions in Solution with Relevance to Birch Reduction.

We investigate the electronic structure of aromatic radical anions in the solution phase employing a combination of liquid-jet (LJ) photoelectron (PE) spectroscopy measurements and electronic structure calculations. By using recently developed protocols, we accurately determine the vertical ionization energies of valence electrons of both the solvent and the solute molecules. In particular, we first characterize the pure solvent of tetrahydrofuran (THF) by LJ-PE measurements in conjunction with ab initio molecular dynamics simulations and G0W0 calculations. Next, we determine the electronic structure of neutral naphthalene (Np) and benzophenone (Bp) as well as their radical anion counterparts Np- and Bp- in THF. Wherever feasible, we performed orbital assignments of the measured PE features of the aromatic radical anions, with comparisons to UV-vis absorption spectra of the corresponding neutral molecules being instrumental in rationalizing the assignments. Analysis of the electronic structure differences between the neutral species and their anionic counterparts provides understanding of the primarily electrostatic stabilization of the radical anions in solution. Finally, we obtain a very good agreement of the reduction potentials extracted from the present LJ-PES measurements of Np- and Bp- in THF with previous electrochemical data from cyclic voltammetry measurements. In this context, we discuss how the choice of solvent holds significant implications for optimizing conditions for the Birch reduction process, wherein aromatic radical anions play crucial roles as reactive intermediates.

Sonic Hedgehog activates prostaglandin signaling to stabilize primary cilium length.

Sonic Hedgehog (SHH) is a driver of embryonic patterning that, when corrupted, triggers developmental disorders and cancers. SHH effector responses are organized through primary cilia (PC) that grow and retract with the cell cycle and in response to extracellular cues. Disruption of PC homeostasis corrupts SHH regulation, placing significant pressure on the pathway to maintain ciliary fitness. Mechanisms by which ciliary robustness is ensured in SHH-stimulated cells are not yet known. Herein, we reveal a crosstalk circuit induced by SHH activation of Phospholipase A2α that drives ciliary E-type prostanoid receptor 4 (EP4) signaling to ensure PC function and stabilize ciliary length. We demonstrate that blockade of SHH-EP4 crosstalk destabilizes PC cyclic AMP (cAMP) equilibrium, slows ciliary transport, reduces ciliary length, and attenuates SHH pathway induction. Accordingly, Ep4-/- mice display shortened neuroepithelial PC and altered SHH-dependent neuronal cell fate specification. Thus, SHH initiates coordination between distinct ciliary receptors to maintain PC function and length homeostasis for robust downstream signaling.