Steven J. Peters

Carbaporphyrin ketals as potential agents for a new photodynamic therapy treatment of leishmaniasis.

Dimethyl and diethyl carbaporphyrin ketals inhibit the growth of Leishmania tarentolae promastigotes in vitro. The concentration dependency of the inhibitory effect was tested using the MTT assay. The presence of reactive oxygen species, such as singlet oxygen and superoxide, was detected using electron paramagnetic resonance spectroscopy with selected spin traps and confocal microscopy in cultures exposed to these carbaporphyrin ketals. These unique porphyrinoids show promise as potent inhibitors of Leishmania.

β-Amino Alcohol Derived β-Hydroxy- and β-(o-Diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides: An Ester−Amide Ligand Structural Model for the Palladium-Catalyzed Allylic Alkylation Reaction

A commercially available collection of beta-amino alcohols have been converted to their corresponding beta-hydroxy- and beta-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides 11a-f and 12a-f and have been employed in the Tsuji-Trost asymmetric alkylation reaction with 1,3-diphenylpropenyl acetate. With the exception of ligands 11b and 11f, the beta-hydroxybenzoyloxy(o-diphenylphosphino)benzamide ligands 11a-f primarily afforded the (R)-enantiomer of the product. In contrast, the bis(phosphine) ligands 12a-f consistently afforded the (S)-enantiomer. The best ligand (12c) was derived from cis-(1R,2S)-2-amino-1,2-diphenyl-1-ethanol, and when applied in the asymmetric allylic alkylation reaction, it yielded the product in an enantiomeric ratio of 97.8.22 favoring the (S)-enantiomer. A computational study was conducted on the conformation that this ligand might adopt in the palladium-catalyzed alkylation reaction as compared to that of the Trost ligand 1a.

Contrasting free energies of electron transfer from [6]- and [8]annulenes to their perdeuteriated and Per-13C analogues

A very large equilibrium isotope effect (confirmed via physical separation of the isotopes involved) was observed via the EPR analysis of a mixture of benzene and perdeuteriated-per- 13 C-benzene competing for a deficient number of electrons in tetrahydrofuran (THF) in the presence of 18-crown-6 (18C6). TheK eq for the reaction C 6 H 6 .- ,K + (18C6)+ 13 C 6 D 6 =C 6 H 6 + 13 C 6 D 6 ,K + (18C6) is 0.096±0.008 at -100 o C

Phenyl Isocyanate Anion Radicals and Their Cyclotrimerization to Triphenyl Isocyanurate Anion Radicals

Room-temperature sodium metal reduction of phenyl isocyanate (PhNCO) in hexamethylphosphoramide yields the anion radical (PhNCO(•-)) where the unpaired electron exhibits coupling to one nitrogen and five unique protons. The extent of coupling to the carbon in the NCO group was obtained via the reduction of (13)C-labeled PhN(13)CO. Remarkably, this coupling is over 2 orders of magnitude smaller than that found for the alkyl-substituted analogue. This large attenuation indicates that the electron is not localized within the isocyanate group (as in the alkyl analogues) but is distributed throughout the entire π system including the phenyl ring. The consequence of this delocalization is that the isocyanate is expected to remain linear upon reduction of PhNCO. The anion radicals of p-tolyl- and p-methoxyphenyl isocyanate have also been generated. We find that these electron-donating substituents on the phenyl ring have little effect on the nitrogen coupling. Hence, the NCO group has the same geometry as the PhNCO(•-). When PhNCO is reduced in tetrahydrofuran, a solvent where ion association effects are common, PhNCO(•-) is not observed. Here, a cyclotrimerization occurs (initiated by PhNCO(•-)), generating the triphenyl isocyanurate anion radical where the unpaired electron is predominately localized in one of the carbonyl moieties.

Contrasting free energies of electron transfer from [6] and [8]annulenes to their erdeuteriated-per-13C analogues

EPR analysis shows that the equilibrium isotope effect upon the equilibrium constant for electron transfer between isotopic isomers is much larger in [6]annulene (i.e. C6H6−. + 13C6D6 = C6H6 + 13C6D6−.) than in the [8]annulene systems (i.e. C8H8−. + 13C8D8 = C8H8 + 13C8D8−.). This is due to the effects of aromaticity.

Tris-[8]annulenyl Isocyanurate Trianion Triradical and Hexa-anion from the Alkali Metal Reduction of [8]Annulenyl Isocyanate.

The solution phase alkali metal reduction of [8]annulenyl isocyanate (C8H7NCO) yields an EPR spectrum, which reveals electron couplings to seven protons and only one nitrogen. Although this strongly suggested that the C8H7NCO anion radical was generated, experiments on the oxidized product reveal the actual reduced species to be tris-[8]annulenyl isocyanurate. Unlike the previously studied phenyl isocyanurate anion radical, the unpaired electron(s) is now localized within an [8]annulenyl moiety. Further exposure to metal results in the formation of an equilibrium mixture of trianion triradical and trianion radical species. The cyclotrimerization to form the isocyanurate is proposed to be driven by a reactive C8H7NCO dianion, which is produced from the large equilibrium disproportionation of the anion radical. Exhaustive reduction of the tris-[8]annulenyl isocyanurate with potassium in THF generates the first-ever observed hexa-anion of an isocyanurate. NMR analysis reveals that the polarity of the carbonyl bonds within this hexa-anion is augmented and is caused by the close proximity of K(+) ions, which are tightly ion paired to the three [8]annulenyl dianion rings. These preliminary studies on the reduction of C8H7NCO suggest that polymeric materials (e.g., polyisocyanates) made from this isocyanate might exhibit unique properties.

Influence of Annulation on the Electron Spin within the 1,2,3-Triazole Ring in Annulenotriazole Anion Radicals

The low temperature (-100 °C) single electron reduction of N1-phenylbenzotriazole in liquid ammonia, and the room temperature reduction of N1-phenylcyclooctatetraenotriazole in hexamethylphosphoramide, yields stable solutions of both anion radicals, which were studied via EPR spectroscopy. The amount of electron spin localized within the triazole ring, and how spin is distributed within this ring, is greatly influenced by the size of the annulene ring attached. UB3LYP/6-31++G(d,p) geometry optimizations using DFT methods were carried out for both anion radicals, and the calculated coupling constants (and electron spin densities) are in good agreement with the EPR spectroscopic results. Both theory and experiment show that much of the unpaired electron spin in the N1-phenylbenzotriazole anion radical is delocalized over the entire π system of benzotriazole ring including the phenyl ring attached, but that a significant percentage of total spin is found to reside within triazole ring with much of it located on the second nitrogen (N2). With the N1-phenylcyclooctatetraenotriazole anion radical, the majority of spin is localized over the π system of the COT ring, however a relatively small amount of total spin, found within the triazole moiety, is largely concentrated on two of the nitrogens (N1 and N3) within the ring.