Dynamic-dependent selectivity in a bisphosphine iron spin crossover C-H insertion/π-coordination reaction.

Reaction pathway selectivity is generally controlled by competitive transition states. Organometallic reactions are complicated by the possibility that electronic spin state changes rather than transition states can control the relative rates of pathways, which can be modeled as minimum energy crossing points (MECPs). Here we show that in the reaction between bisphosphine Fe and ethylene involving spin state crossover (singlet and triplet spin states) that neither transition states nor MECPs model pathway selectivity consistent with experiment. Instead, single spin state and mixed spin state quasiclassical trajectories demonstrate nonstatistical intermediates and that C-H insertion versus π-coordination pathway selectivity is determined by the dynamic motion during reactive collisions. This example of dynamic-dependent product outcome provides a new selectivity model for organometallic reactions with spin crossover.

Potent Anti-Inflammatory, Arylpyrazole-Based Glucocorticoid Receptor Agonists That Do Not Impair Insulin Secretion.

Glucocorticoids (GCs) are widely used in medicine for their role in the treatment of autoimmune-mediated conditions, certain cancers, and organ transplantation. The transcriptional activities GCs elicit include transrepression, postulated to be responsible for the anti-inflammatory activity, and transactivation, proposed to underlie the undesirable side effects associated with long-term use. A GC analogue that could elicit only transrepression and beneficial transactivation properties would be of great medicinal value and is highly sought after. In this study, a series of 1-(4-substituted phenyl)pyrazole-based GC analogues were synthesized, biologically screened, and evaluated for SARs leading to the desired activity. Activity observed in compounds bearing an electron deficient arylpyrazole moiety showed promise toward a dissociated steroid, displaying transrepression while having limited transactivation activity. In addition, compounds 11aa and 11ab were found to have anti-inflammatory efficacy comparable to that of dexamethasone at 10 nM, with minimal transactivation activity and no reduction of insulin secretion in cultured rat 832/13 beta cells.

Gas-Phase Ion Chemistry of Metalloporphyrin Anions with Molecular Oxygen: Probing the Influence of the Oxidation and Spin State of the Central Transition Metal by Experiment and Theory.

We performed a comprehensive gas-phase experimental and quantum-chemical study of the binding properties of molecular oxygen to iron and manganese porphyrin anions. Temperature-dependent ion-molecule reaction kinetics as probed in a Fourier-transform ion-cyclotron resonance mass spectrometer reveal that molecular oxygen is bound by, respectively, 40.8 ± 1.4 and 67.4 ± 2.2 kJ mol-1 to the FeII or MnII centers of isolated tetra(4-sulfonatophenyl)metalloporphyrin tetraanions. In contrast, FeIII and MnIII trianion homologues were found to be much less reactive-indicating an upper bound to their dioxygen binding energies of 34 kJ mol-1. We modeled the corresponding O2 adsorbates at the density functional theory and CASPT2 levels. These quantum-chemical calculations verified the stronger O2 binding on the FeII or MnII centers and suggested that O2 binds as a superoxide anion.