An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), was the most significant infectious disease killer globally until the advent of COVID-19. Mtb has evolved to persist in its intracellular environment, evade host defenses, and has developed resistance to many anti-tubercular drugs. One approach to solving resistance is identifying existing approved drugs that will boost the host immune response to Mtb.

Michael addition reactions with eta2-coordinated anisoles: controlling the stereochemistry of the para and benzylic carbons.

Several eta(2)-coordinated anisole complexes were treated with various Michael acceptors in the presence of a Lewis or Bronsted acid to generate stable 4H-anisolium complexes. These reactions were found to proceed with high stereochemical control with predictable outcomes, provided that the moderate acid (NH(2)Ph(2))OTf was used and the complex was dissolved in an acidic solution. The stereochemistry is shown to originate from an unexpectedly high preference for one coordination diastereomer of the anisole complex in the solid state and a Diels-Alder like transition state for the Michael reaction.

Transition metal-stabilized arenium cations: protonation of arenes dihapto-coordinated to pi-basic metal fragments.

A series of metal complexes was synthesized in which arenes were dihapto-coordinated to pi-basic metal fragments having the general form [TpM(pi-acid)(L)], where Tp = hydridotris(pyrazolyl)borate, M = rhenium, molybdenum, or tungsten, pi-acid = CO or NO(+), and L = 1-methylimidazole, 1-butylimidazole, pyridine, or trimethylphosphine. The arene complexes were shown to be significantly more basic than the analogous pentaammineosmium(II) arene complexes and were protonated by moderate acids to give remarkably stable eta(2) and eta(3) arenium cation complexes. A crystal structure of [TpRe(CO)(MeIm)(5,6-eta(2)-2H-anisolium)](OTf) confirmed the eta(2) coordination of the anisolium ligand, but suggests a weak long-range interaction between the metal and C1 of the anisolium.

Diastereo- and enantioselective dearomatization of rhenium-bound naphthalenes.

Dihapto-coordinated naphthalene complexes of the form TpRe(CO)(L)(eta(2)-naphthalene) (L = PMe(3), pyridine, or 1-methylimidazole) undergo electrophilic addition with dimethoxymethane and with various Michael acceptors to generate 1H-naphthalenium species. These naphthalenium complexes undergo intra- or intermolecular nucleophilic addition reactions with stabilized enolates, silyl ketene acetals, or enols to form the corresponding dihydronaphthalene complexes. Oxidative decomplexation generates the free dihydronaphthalene.

Solid-state induced control of kinetically unstable stereoisomers.

Arene complexes of the form TpM(pi-acid)(L)(eta2-arene) (Tp = hydridotris(pyrazolyl)borate, M = Re, Mo, or W, pi-acid = CO or NO, L = 1-alkylimidazole, pyridine, PMe3, arene is prochiral) exist as a dynamic equilibrium of coordination diastereomers in solution. In both crystalline and amorphous solid states, however, only one diastereomer is present. Reactions on the bound arenes in these complexes have been performed stereoselectively, by exploiting the homomorphic nature of the solid phase.

Binding and activation of aromatic molecules by a molybdenum pi-base.

Compounds having the form TpMo(NO)(1-methylimidazole)(eta(2)-L(pi)) (Tp = hydridotris(pyrazolyl)borate; L(pi) = cyclohexene, naphthalene, furan, thiophene, and acetone) were synthesized in 31-41% yield by the reduction of TpMo(NO)Br(2) in the presence of 1-methylimidazole and the respective pi-acidic organic ligand. The structure of the naphthalene complex was confirmed by single-crystal X-ray diffraction. Degradation studies showed the bound aromatics to have half-lives of 37-236 h in acetone solution at 20 degrees C.