Pyridine N-alkylation by lithium, magnesium, and zinc alkyl reagents: synthetic, structural, and mechanistic studies on the bis(imino)pyridine system

The 2,6-bis(alpha-iminoalkyl)pyridines 2,6-[ArNC(CR(3))](2)C(5)H(3)N [R = H, D; Ar = 2,6-i-Pr(2)C(6)H(3) (DIPP), 2,6-Me(2)C(6)H(3) (DMP)] react with MeLi in Et(2)O to give a binary mixture of products: the pyridine N-methylated species 2,6-[ArNC(CR(3))](2)C(5)H(3)N(Me)Li(OEt(2)) and the deprotonated/dedeuterated species 2-[ArNC(CR(3))],6-[ArNC(=CR(2))]C(5)H(3)NLi(OEt(2)). For R = D, the product ratio is 2:1 in favor of the N-methylated product, while, for R = H, the deprotonated product is favored by 5:1, increasing to 8:1 in toluene solvent. Warming solutions of the N-methylated species leads to clean conversion to the thermodynamically preferred deprotonated species. Crossover experiments show that MeLi is re-formed and dissociates from the terdentate ligand before deprotonating the ketimine methyl unit. For MgR(2) (R = Et, i-Pr) and ZnR(2) (R = Et) reagents, N-alkylation products are formed exclusively, but derivatives containing bulky aryl substituents are found to undergo further rearrangement to 2-alkylated species, arising by migration of the alkyl group of the N-alkyl moiety to the adjacent ring carbon atom. The reversibility of the N-alkylation process has been probed using deuterio-labeled Mg alkyl reagents and mixed alkyl zinc species. A cationic zinc derivative is shown to undergo "reverse" alkyl migration, from the heterocycle nitrogen atom to the zinc center. EPR spectroscopy reveals a paramagnetic intermediate in which the unpaired electron is delocalized over the heterocycle and di-imine moieties of the ligand, indicating that the N-alkylation reactions proceed via single electron-transfer processes.     

A Study of the 13C NMR Shifts in Two Tetradehydrocyclodecabiphenylenes and Related Aryl and Biphenylenylacetylenes

The ¹³C spectra of 5,6,9,10-tetradehydrocyclodeca[1,2,3,4-def]-benzo [7,8]biphenylene, 1, and 5,6,9,10-tetradehydrocyclodeca [1,2,3,4-def]-naphtho [2,3-7,8]biphenylene, 2, are reported as are those of a number of simpler acetylenic hydrocarbons used as spectral references. Most of the shifts can be assigned unambiguously. The acetylenic shift assignments were verified by ortho-proton, sp-carbon (¹H(1)-¹³C_sp(3)) decoupling experiments. A simple additive shift correlation is found for the hydrocarbons containing unstrained acetylenic groups. However, significant discrepencies are found for the ¹³C shifts for the strained hydrocarbons 1, 2, 1,2-bis(phenylethynyl)-benzene, 12, and 2,3-bis(phenylethynyl)-naphthalene, 13. The discrepencies are particularily large for carbons near the triple bonds and are attributed to a combination of strain, rehybridization, and other proximity effects related to the interaction between the ortho-substituted acetylenic carbons.     

ACUTE SKIN RESPONSE IN ALBINO MICE FOLLOWING PORPHYRIN PHOTOSENSITIZATION UNDER OXIC AND ANOXIC CONDITIONS

Abstract Acute normal skin toxicity induced by porphyrin photosensitization has been examined using albino mice. Oxic and anoxic (clamped) skin was exposed to red light (630 nm) 24 h following administration of hematoporphyrin derivative (HpD) or Photofrin II (the active component of HpD). Experiments were also performed to determine the effect of sodium pentobarbital anesthesia on HpD and Photofrin II photosensitization of normal skin. Results from this study demonstrated that comparable levels of acute skin damage were induced by HpD and Photofrin II under oxic conditions but neither porphyrin produced any apparent phototoxicity under anoxic conditions. In addition, the level of skin damage induced by porphyrin photosensitization was not affected by sodium pentobarbital anesthesia.     

Fragmentation of organic anions induced by exothermic addition reactions

The addition reactions of a series of carbanions with CO₂, COS and CS₂ have been studied in a flowing afterglow apparatus. Carbon dioxide simply forms the adduct, but the more highly exothermic additions to COS and CS₂ lead both to addition and addition followed by fragmentation. A number of novel fragmentation pathways have been observed for additions to diazo anions and to anions derived by proton abstraction from allenes. In addition to these reactions, highly basic anions are observed to undergo sulfur atom transfer reactions with CS₂.     

Solvent-extraction and Langmuir-adsorption-based transport in chemically functionalized nanopore membranes

We have investigated the transport properties of nanopore alumina membranes that were rendered hydrophobic by functionalization with octadecyltrimethoxysilane (ODS). The pores in these ODS-modified membranes are so hydrophobic that they are not wetted by water. Nevertheless, nonionic molecules can be transported from an aqueous feed solution on one side of the membrane, through the dry nanopores, and into an aqueous receiver solution on the other side. The transport mechanism involves Langmuir-type adsorption of the permeating molecule onto the ODS layers lining the pore walls, followed by solid-state diffusion along these ODS layers; we have measured the diffusion coefficients associated with this transport process. We have also investigated the transport properties of membranes prepared by filling the ODS-modified pores with the water-immiscible (hydrophobic) liquid mineral oil. In this case the transport mechanism involves solvent extraction of the permeating molecule into the mineral oil subphase confined with the pores, followed by solution-based diffusion through this liquid subphase. Because of this different transport mechanism, the supported-liquid membranes show substantially better transport selectivity than the ODS-modified membranes that contain no liquid subphase.     

Mercury(II) mediated cyclisation of R-1-(1′-hydroxyethyl)-2-(1″-propenyl)-3-alkoxy-4-methoxybenzenes to chiral isochromanes

A protocol has been established for the transformation of chiral ortho 1-hydroxyethyl propenyl benzenes under both anaerobic and oxidative mercury(II) mediated conditions to produce chiral isochromanes. Further transformations of the former products yielded chiral isochromanquinones, while the latter afforded the corresponding chiral 4-hydroxyisochromanquinones.     

Preparation and reactions of the (dicarbonyl)(η5-cyclopentadienyl)(tetrahydrofuran)iron cation: A convenient route to (dicarbonyl)(η5-cyclopentadiemyl)(η2-olefin)iron cations and related complexes

The versatile reagent [η⁵-C₅H₅)Fe(CO)₂(THF)]BF₄ has been isolated from the reaction of (η₅-C₅H₅)Fe(CO)₂I and AgBF₄ in THF and shown to react in CH₂Cl₂ with olefins to yield [(η⁵-C₅H₅)Fe(CO)₂(η²-olefin)]BF₄ complexes. For most olefins the yields are high. The yield in these reactions can be increased by treating the CH₂Cl₂ solution of [(η⁵-C₅H₅)Fe(Co)₂(THF)]BF₄ and olefin with gaseous BF₃ in order to complex the THF as the BF₃-THF adduct. Most striking is the increase in yield for the cyclohexene complex from 17% to 92%.     

4-carboxy-1,2-cyclohexanedionedioxime complexes of nickel(ii) in alkaline media

The reactions of 4-carboxy-1,2-cyclohexanedionedioxime and nickel(II) were studied in alkaline media. Spectrophotometric studies indicate the presence of a 1:1 complex ion, NiD^-. Magnetic susceptibility measurements on a series of solutions of varying ratios of vic-dioxime and nickel(II) showed that the 1:1 complex ion was diamagnetic and that two paramagnetic complexes, probably NiD₂^4- and NiD₃^7-, are present in solution. The stability constants for the three complexes were calculated from spectrophotometric and magnetic susceptibility data. The log K values were found to be log K₁ = 28.74 ± 0.60, log K₂ = 0.76 ± 0.15, and log K₃ = 3.67 ± 0.73, respectively.     

Conformational equilibria and photoinduced tautomerization in 2-(2′-pyridyl)pyrrole

Depending on the polarity and protic abilities of the solvent, 2-(2′-pyridyl)pyrrole can exist in either syn or anti rotameric forms. In nonpolar solvents, intramolecular excited state single proton transfer is observed, manifested by the appearance of low-energy tautomeric emission. The solvent-assisted excited state double proton transfer reaction is also detected. DFT calculations confirm low barriers for both single and double proton transfer processes in the lowest excited singlet state and show different character of the tautomerization in both cases: in the intramolecular reaction, mutual approach of two nitrogen atoms plays an important role.     

Protein biosensors based on biofunctionalized conical gold nanotubes

There is increasing interest in the concept of using nanopores as the sensing elements in biosensors. The nanopore most often used is the alpha-hemolysin protein channel, and the sensor consists of a single channel embedded within a lipid bilayer membrane. An ionic current is passed through the channel, and analyte species are detected as transient blocks in this current associated with translocation of the analyte through the channel-stochastic sensing. While this is an extremely promising sensing paradigm, it would be advantageous to eliminate the very fragile lipid bilayer membrane and perhaps to replace the biological nanopore with an abiotic equivalent. We describe here a new family of protein biosensors that are based on conically shaped gold nanotubes embedded within a mechanical and chemically robust polymeric membrane. While these sensors also function by passing an ion current through the nanotube, the sensing paradigm is different from the previous devices in that a transient change in the current is not observed. Instead, the protein analyte binds to a biochemical molecular-recognition agent at the mouth of the conical nanotube, resulting in complete blockage of the ion current. Three different molecular-recognition agents, and correspondingly three different protein analytes, were investigated: (i) biotin/streptavidin, (ii) protein-G/immunoglobulin, and (iii) an antibody to the protein ricin with ricin as the analyte.