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Effects of substituents on the lengths of the central C–C single bond in the butterfly-shaped anthracene photodimers (1)–(7) and lepidopterenes (8) are studied. X-Ray analysis of the photodimer (10) of 9,10-difluoroanthracene gave a C(9)–C(10′) bond length of 1.631 (3)A. An attempt to re-determine molecular structure of the photoisomer (5) of [2.2](9,10) anthracenophane (12) by neutron diffraction analysis is also reported [C(9)–C(10′): obs. 1.64(1), calc. 1.63(1)A]. The D2 structure that had been proposed for the minimum-energy conformation of (5) is questioned and the D2h symmetric conformation is suggested on the basis of the diffraction results and MNDO calculations. The experimentally determined distances of the long central C–C bonds in these butterfly compounds including dianthronyl (9) are well reproduced by MNDO calculations with a standard deviation of 0.013 A. Small but significant further elongation of the central C–C bond by up to 0.07 A resulting from annulation of cyclobutane or cyclopentane ring in anthracene photodimers and from remote chlorine substitution in lepidopterene are interpreted in terms of the increased π→σ* orbital interaction.

La pyrolyse en phase gazeuse du compose du titre produit le bicyclobutane fortement excite du point de vue vibrationnel

Synthese du compose du titre par ozonolyse du phenyl-2 bicyclo [1.1.1] pentanol-2. La pyrolyse conduit par cycloreversion a l'allylcetene. La photolyse conduit par decarboxylation au bicyclobutane

Neutral macrocycle 1b shows a substantial binding affinity for quaternary ammonium and immonium compounds in chloroform due to ion-dipole attractions.

The microwave spectra of five isotopic species of bicyclo (1.1.1) pentanone have been investigated. The rotational constants along with various centrifugal distortion constants for each species have been determined. From the rotational constants, a complete r(s) structure has been determined for the heavy atoms. Analysis of Stark effect measurements has shown the dipole moment to be along the a principal inertial axis with a magnitude of 3.164 (5) D. These results are compared with those obtained by four current theoretical methods: molecular mechanics (MM2), MNDO, and Hartree-Fock ab initio theory with STO-3G and 3-21G basis sets.

NMR evidence establishes that both diastereomers of 1,2-diphenyl-1,2-bis(4-pyridyl)ethane (2), identified by optical resolution of the racemic form, exist predominantly in the anti conformation. Furthermore, empirical force field calculations show that the gauche conformer of 1,1,2,2-tetrakis(2,6-dimethylphenyl)ethane (3) is less stable by ca. 10 kcal mol than the anti structure. It thus appears that neither polar effects nor steric congestion are effective in reversing the marked preference of 1,1,2,2-tetraphenylethane (1) and other unclamped tetraarylethanes for an anti ground state. In contrast, as predicted by empirical force field calculations and confirmed by X-ray and NMR evidence, the ground state structure of 9,9'-bifluorenyl (4) is gauche. The conformational behavior of 1–4 is discussed in terms of the intramolecular aryl ring stacking in clamped and unclamped tetraarylethanes.

We have investigated aspects of ion selectivity in K+ channels by functional expression of wild-type and mutant heteromultimeric G protein-coupled inward-rectifier K+ (GIRK) channels in Xenopus oocytes. Within the K+ channel pore (P) region signature sequence, a large number of point mutations in GIRK1 and GIRK4 subunits have been made at a key tyrosine residue—the “signature” tyrosine of the GYG. Studies of mutant GIRK1/GIRK4 heteromultimers reveal that the GIRK1 and GIRK4 subunits contribute asymmetrically to K+ selectivity. The signature tyrosine of GIRK1 can be mutated to many different residues while retaining selectivity; in contrast, the analogous position in GIRK4 must be tyrosine for maximum selectivity. Other residues of the P region also contribute to selectivity, and studies with GIRK1/GIRK4 chimeras reveal that an intact, heteromultimeric P region is necessary and sufficient for optimal K+ selectivity. We propose that the GIRK1 and GIRK4 P regions play roles similar to the two P regions of an emerging family of K+ channels whose subunits each have two P regions connected in tandem. We find different consequences between similar mutations in inward-rectifier and voltage-gated K+ channels, which suggests that the pore structures and selectivity mechanisms in the two classes of channel may not be identical. We confirm that GIRK4 subunits alone can form functional channels in oocytes, but we find that these channels are measurably permeable to Na+ and Ca2+.

SummaryNicotinic acetylcholine receptors (nAChRs) are vital to neuronal signaling, are implicated in important processes such as learning and memory, and are therapeutic targets for neural diseases. The α7 nAChR has been implicated in Alzheimer's disease and schizophrenia, and allosteric modulators have become one focus of drug development efforts. We investigate the mode of action of the α7-selective positive allosteric modulator, PNU-120596, and show that the higher potency of acetylcholine in the presence of PNU-120596 is not due to an altered agonist binding site. In addition, we propose several residues in the gating interface and transmembrane region that are functionally important to transduction of allosteric properties, and link PNU-120596, the acetylcholine binding region, and the receptor gate. These results suggest global protein stabilization from a communication network through several key residues that alter the gating equilibrium of the receptor while leaving the agonist binding properties unperturbed.

We report on the first, to our knowledge, successful detection of a fluorescent unnatural amino acid (fUAA), Lys(BODIPYFL), incorporated into a membrane protein (the muscle nicotinic acetylcholine receptor, nAChR) in a living cell. Xenopus oocytes were injected with a frameshift-suppressor tRNA, amino-acylated with Lys(BODIPYFL) and nAChR (alpha/beta19'GGGU/gamma/delta) mRNAs. We measured fluorescence from oocytes expressing nAChR beta19'Lys(BODIPYFL), using time-resolved total internal reflection fluorescence microscopy. Under conditions of relatively low receptor density (0.1 receptors/microm(2)), we observed puncta with diffraction-limited profiles that were consistent with the point-spread function of our microscope. Furthermore, diffraction-limited puncta displayed step decreases in fluorescence intensity, consistent with single-molecule photobleaching. The puncta densities agreed with macroscopic ACh-induced current densities, showing that the fUAA was incorporated, and that receptors were functional. Dose-response relations for the nAChR beta19'Lys(BODIPYFL) receptors were similar to those for wild-type receptors. We also studied nAChR beta19'Lys(BODIPYFL) receptors labeled with alpha-bungarotoxin monoconjugated with Alexa488 (alphaBtxAlexa488). The nAChR has two alphaBtx binding sites, and puncta containing the Lys(BODIPYFL) labeled with alphaBtxAlexa488 yielded the expected three discrete photobleaching steps. We also performed positive control experiments with a nAChR containing enhanced green fluorescent protein in the gamma-subunit M3-M4 loop, which confirmed our nAChR beta19'Lys(BODIPYFL) measurements. Thus, we report on the cell-based single-molecule detection of nAChR beta19'Lys(BODIPYFL).

There is much current interest in the design and synthesis of water-soluble organic molecules with hydrophobic binding sites. A variety of interesting artificial receptors (hosts) based on cyclophane skeletons has been prepared and shown to bind flat, aromatic guests very efficiently. In contrast, efforts to bind other types of guests, such as derivatives of polycyclic aliphatic systems, have been less successful. We report herein that a new class of receptor molecules, which we have designed and synthesized, 7 binds a guest of this second type very effectively. Two binding modes are seen: one in which the guest is bound in a relatively random orientation and one which involves very much stronger binding with a very precise orientation of the guest in the binding site.

Observation directe de l'etat triplet du compose cite dans le titre par spectroscopie RPE et etude de ses comportements thermiques

The title diazene 1 has been synthesized and shown to decompose thermally to cyclobutadiene over a surprisingly small barrier.

La pyrolyse en phase gazeuse du compose du titre produit le bicyclobutane fortement excite du point de vue vibrationnel

La photolyse de diaza-2,3bicyclo [2.2.1] heptenes-2 avec des groupes spirocyclopropyl en position 7 donne des diradicaux alkylidene-2 cyclopentanediyles-1,3

Observation directe de l'etat triplet du compose cite dans le titre par spectroscopie RPE et etude de ses comportements thermiques