Ethynyl pi-extended 2,5-diphenyl-1,3,4-oxadiazoles and 2-phenyl 5-(2-thienyl)-1,3,4-oxadiazoles: synthesis, X-ray crystal structures and optical properties

2-(4-tert-Butylphenyl)-5-(4-ethynylphenyl)-1,3,4-oxadiazole reacts with a series of heteroaryl iodides under standard Sonogashira cross-coupling conditions (Pd[PPh(3)](2)Cl(2), CuI, triethylamine, THF) to yield products 2a-g in 40-79% yields (heteroaryl = 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazyl, 5-bromo-2-pyrimidyl, 2-thienyl and 3-thienyl, respectively). Compound 2f was lithiated followed by electrophilic iodination (BuLi, perfluorohexyl iodide) to give 3, which by a two-step sequence gave the terminal ethynylthienyl derivative 5. Conversion of 5 into the terminal ethynylaldehyde derivative 7, via acetal derivative 6, proceeded in high yield. Starting from 2-iodo-5-methoxycarbonylthiophene, a five-step sequence afforded 2-(4-tert-butylphenyl)-5-(4-ethynylthienyl)-1,3,4-oxadiazole 13 (13% overall yield). Reactions of 13 gave terminal pyridyl, pyrazyl, pyrimidyl and thienyl derivatives, analogous to those obtained from 1. Two-fold reaction of 13 with 2,5-diiodothiophene gave the bis(ethynylthienyl)thiophene derivative 15 (30% yield). Solution UV-Vis absorption and photoluminescence spectra establish that replacement of the phenyl ring in the 2,5-diphenyl-1,3,4-oxadiazole series 2a-g by a thienyl ring [i.e. the 2-phenyl-5-(2-thienyl)-1,3,4-oxadiazole series 14a-g] leads to a red shift in the lowest energy band in both the absorption spectra and emission spectra. The X-ray crystal structures of compounds 2d, 2g, 5 and 14d.CHCl(3) reveal that the molecular structures are approximately planar although there are substantial differences in the conformations.     

A (pi-extended tetrathiafulvalene)-fluorene conjugate. Unusual electrochemistry and charge transfer properties: the first observation of a covalent D(2+)-sigma-A(.-) redox state(1)

The synthesis of novel electrochemically amphoteric TTFAQ-sigma-A compounds (TTFAQ = 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene, sigma = saturated spacer, A = polynitrofluorene acceptor) is reported. Their solution redox behavior is characterized by three single-electron reduction and one two-electron oxidation waves. Electrochemical quasireversibility of the TTFAQ(2+) state and a low E(ox) - E(red) gap ( approximately 0.25 V) for 3-(9-dicyanomethylene-4,5,7-trinitrofluorene-2-sulfonyl)-propionic acid 2-[10-(4,5-dimethyl-[1,3]dithiol-2-ylidene)-9,10-dihydroanthracen-9-ylidene]-5-methyl-[1,3]dithiol-4-ylmethyl ester (10) has enabled the electrochemical generation of the hitherto unknown transient D(2+)-sigma-A(.-) state as observed in cyclic voltammetry and time-resolved spectroelectrochemistry. The ground state of compound 10 was shown to be ionic in the solid but is essentially neutral in solution (according to electron paramagnetic resonance). The X-ray structure of an intermolecular 1:2 complex between 2-[2,7-bis(2-hydroxyethoxy)-9,10-bis(4,5-dimethyl-[1,3]dithiol-2-ylidene)-9,10-dihydroanthracene and 2,5,7-trinitro-4-bromo-9-dicyanomethylenefluorene, 14.(17)(2), reveals, for the first time, full electron transfer in a fluorene charge-transfer complex.     

Experimental and theoretical determination of nucleic acid magnetic susceptibility: importance for the study of dynamics by field-induced residual dipolar couplings

Magnetic susceptibility anisotropies (Deltachi) are determined for the nucleic acid bases on the basis of a combined NMR spectroscopic and DFT study. Magnetic field-induced residual dipolar couplings (RDC) measured for the Dickerson dodecamer allow for the determination of a precise value of Deltachi for this DNA. A tensor summation employing the results of DFT calculations of the individual base magnetic susceptibility tensors and the known structure of the dodecamer provides a value of Deltachi which is in excellent agreement with experiment. The DFT results are shown to provide superior agreement with experiment for the dodecamer and a protein-DNA complex when compared with other sets of values in common use in the literature. The marked discrepancy between our Deltachi values and existing sets of values has a direct and significant impact on the interpretation of field-induced anisotropic interactions in terms of biomolecular structure and dynamics.     

Role of membrane potential and hydrogen bonding in the mechanism of translocation of guanidinium-rich peptides into cells

The results described herein support a mechanistic hypothesis for how guanidine-rich transporters attached to small cargos (MW ca. <3000) can migrate across the lipid membrane of a cell and directly enter the cytosol. Arginine oligomers are found to partition almost completely into the aqueous layer of a water-octanol bilayer. However, when the same partitioning experiment is conducted in the presence of sodium laurate, a representative negatively charged membrane constituent, the arginine oligomer partitions almost completely (>95%) into the octanol layer. In contrast, ornithine oligomers partition almost exclusively into the water layer with and without added sodium laurate. The different partitioning between guanidinium-rich and ammonium-rich oligomers in the presence of sodium laurate is consistent with the ability of the former to form a bidentate hydrogen bonded ion pair. Mono- and dimethylated arginine oligomers, which like ornithine can only efficiently form monodentate hydrogen bonds, were prepared and found to exhibit poor cellular uptake. Ion pair formation converts a once water-soluble agent to a lipid-soluble agent, thereby reducing the energetic penalty for passage of guanidine-rich transporters through the lipid bilayer. Uptake of guanidine-rich transporters is known to be an energy-dependent process, and this requirement for cellular ATP is now rationalized by the inhibition of guanidine-rich transporter uptake in the presence of agents that reduce the membrane potential. Specifically, incubation of cells in buffers with high potassium ion concentrations or pretreatment of cells with gramicidin A reduces the cellular uptake of Fl-aca-arg8-CONH2 by >90%. Furthermore, the reciprocal experiment of hyperpolarizing the cell with valinomycin increased uptake by >1.5 times. In summary, we propose that the water-soluble, positively charged guanidinium headgroups of the transporter form bidentate hydrogen bonds with H-bond acceptor functionality on the cell surface. The resultant ion pair complexes partition into the lipid bilayer and migrate across at a rate related to the membrane potential. The complex dissociates on the inner leaf of the membrane, and the transporter enters the cytosol. This hypothesis does not preclude uptake by other mechanisms, including endocytosis, which is likely to dominate with large cargos.     

Engineering a remarkably low HOMO-LUMO gap by covalent linkage of a strong pi-donor and a pi-acceptor--tetrathiafulvalene-sigma-polynitrofluorene diads: their amphoteric redox behavior,electron transfer and spectroscopic properties

Novel R3TTF-sigma-A compounds 14, 16 and 19 (R3TTF = trial-kyletrathiafulvalene, sigma = saturated spacer, A = polynitrofluoren-9-dicyano-methylene acceptor) incorporating very strong donor and acceptor moieties have been synthesized by condensation of the corresponding R3TTF-sigma-fluoren-9-one diads with malononitrile. Reversible five-step amphoteric redox behavior has been observed with an extremely low HOMO-LUMO gap (approximately 0.3 eV). For compound 14 a strong EPR signal is observed in the solid state, ascribed to intermolecular complexation: a less intense signal is seen in solution, corresponding to ca. 2% of the molecules existing in a radical form at room temperature. Intramolecular charge transfer in diads 14 and 16 is manifested in strong absorption bands in the near-IR region of their electronic spectra. Spectroelectrochemical data reveal marked electrochromic behavior in the visible and near-IR region of both compounds. The first X-ray crystal structure of a fluorene radical-anion salt is reported, namely the copper salt of 2,4,5,7-tetranitro-9- dicyanomethylenefluorene (1:1 stoichiometry).     

Coupled cluster calculations provide a one‐to‐one mapping between calculated and observed transition energies in the electronic absorption spectrum of zinc phthalocyanine

All transitions in the experimentally designated and numbered Q, B, and N bands (< 4.8 eV) of the electronic absorption spectrum of zinc phthalocyanine (ZnPc) are assigned on the basis of one‐to‐one agreement between calculated and experimentally observed transition energies and oscillator strengths. Each band in this range of the spectrum represents a ligand‐based transition that originates from a combination of occupied orbitals and terminates in the lowest unoccupied molecular orbital (LUMO, ). Transition energies in the L and C regions (4.8–6.5 eV) are harder to capture quantitatively, due to the partial Rydberg character of some of the excited states, and so are tentatively assigned here. Most transitions in this range correspond to excitations from the HOMO or lower‐energy orbitals to π orbitals above the LUMO.     

Alkaline earth chloride hydrates: chlorine quadrupolar and chemical shift tensors by solid-state NMR spectroscopy and plane wave pseudopotential calculations

A series of alkaline earth chloride hydrates has been studied by solid-state (35/37)Cl NMR spectroscopy in order to characterize the chlorine electric field gradient (EFG) and chemical shift (CS) tensors and to relate these observables to the structure around the chloride ions. Chlorine-35/37 NMR spectra of solid powdered samples of pseudopolymorphs (hydrates) of magnesium chloride (MgCl(2).6H(2)O), calcium chloride (CaCl(2).2H(2)O), strontium chloride (SrCl(2), SrCl(2).2H(2)O, and SrCl(2).6H(2)O), and barium chloride (BaCl(2).2H(2)O) have been acquired under stationary and magic-angle spinning conditions in magnetic fields of 11.75 and 21.1 T. Powder X-ray diffraction was used as an additional tool to confirm the purity and identity of the samples. Chlorine-35 quadrupolar coupling constants (C(Q)) range from essentially zero in cubic anhydrous SrCl(2) to 4.26+/-0.03 MHz in calcium chloride dihydrate. CS tensor spans, Omega, are between 40 and 72 ppm, for example, Omega= 45+/-20 ppm for SrCl(2).6H(2)O. Plane wave-pseudopotential density functional theory, as implemented in the CASTEP program, was employed to model the extended solid lattices of these materials for the calculation of their chlorine EFG and nuclear magnetic shielding tensors, and allowed for the assignment of the two-site chlorine NMR spectra of barium chloride dihydrate. This work builds upon our current understanding of the relationship between chlorine NMR interaction tensors and the local molecular and electronic structure, and highlights the particular sensitivity of quadrupolar nucleus solid-state NMR spectroscopy to the differences between various pseudopolymorphic structures in the case of strontium chloride.