Molecular model of the neural dopamine transporter

The dopamine transporter (DAT) regulates the action of dopamine by reuptake of the neurotransmitter into presynaptic neurons, and is the main molecular target of amphetamines and cocaine. DAT and the Na⁺/H⁺ antiporter (NhaA) are secondary transporter proteins that carry small molecules across a cell membrane against a concentration gradient, using ion gradients as energy source. A 3-dimensional projection map of the E. coli NhaA has confirmed a topology of 12 membrane spanning domains, and was previously used to construct a 3-dimensional NhaA model with 12 trans-membrane -helices (TMHs). The NhaA model, and site directed mutagenesis data on DAT, were used to construct a detailed 3-dimensional DAT model using interactive molecular graphics and empiric force field calculations. The model proposes a dopamine transport mechanism involving TMHs 1, 3, 4, 5, 7 and 11. Asp79, Tyr252 and Tyr274 were the primary cocaine binding residues. Binding of cocaine or its analogue, (–)-2-carbomethoxy-3-(4-fluorophenyl)tropane (CFT), seemed to lock the transporter in an inactive state, and thus inhibit dopamine transport. The present model may be used to design further experimental studies of the molecular structure and mechanisms of DAT and other secondary transporter proteins.     

Gas‐Phase Electron‐Diffraction Investigation and Quantum‐Chemical Calculations of the Structure of 1,5‐Dimethylsemibullvalene‐2,4,6,8‐tetracarboxylic Dianhydride

The bridged homotropilidines have been of interest for decades because their molecules offer the potential for homoaromaticity. Although many of these have been shown not to be homoaromatic, the energy differences of the delocalized (homoaromatic) forms and the localized (nonhomoaromatic) ones, and the barriers to the interconversion of the localized forms via a Cope rearrangement, have been found to vary greatly. The title compound is a strong candidate for homoaromaticity, and, since the structures of the possible localized and delocalized forms could differ significantly, we have carried out an electron‐diffraction investigation of it augmented by quantum‐mechanical calculations with different basis sets at several levels of theory. Three models were explored: one representing a localized form of C_s symmetry, one a delocalized form of C_2v symmetry, and one a 2 : 1 mixture of the localized/delocalized forms. Although none of the models could be ruled out, the experimental evidence slightly favors the C_s form. These results are consistent with those from the DFT B3PW91 calculations with basis sets ranging from 6‐31G(d) to cc‐pVTZ, which, surprisingly, predict essentially equal thermally corrected free energies for each. The results are discussed.     

Theoretical Investigation of the C2H2B2 Potential Energy Surface

Fifteen unique energy minima and thirteen transition states on the C ₂H₂B₂ potential surface have been located and optimized at the MP2 level of theory with the 6-311G(d,p) basis set. The planar four-membered ring isomer , 1, an analog of cyclobutadiene, is a transition state lying 37 kcal/mol above the nonplanar four-membered ring , 3. The planar , 10, is the second most stable species found, lying 72.2 kcal/mol below 3. The nonplanar, butterfly-shaped ring, 4, is a local minimum 33.7 kcal/mol more stable than 3. A four-membered ring isomer with alternating boron–carbon locations, , 5, lies 67.0 kcal/mol below 3 and 33.3 kcal/mol below 4. The ring of 5 is planar with one hydrogen above and one below the plane (C _2h symmetry). The borylene-substituted boracyclopropene, , 8, is a planar local minimum lying 36.0 kcal/mol above 5. The most stable C₂H₂B₂ isomer found was the planar, four-membered ring system 22 (D _2h symmetry) composed of two BCC three-membered rings fused across the C-C bond. Structure 22 lies 22.2 kcal/mole below 10, 105.4 kcal/mol below 3, 71.7 kcal/mol below 4, and 38.2 kcal/mol below 5. Isomer 22 is the structural analog of the trialene form of C₄H₂. The most stable linear isomer, HB BH, 26, was surprisingly 50.5 kcal/mol less stable than 22. The stabilities of the two most stable cyclic isomers 10 and 22 may be explained by aromaticity.     

Orbital-invariant formulation and second-order gradient evaluation in Møller-Plesset perturbation theory

Based on the Hylleraas functional form, the second and third orders of Møller-Plesset perturbation theory are reformulated in terms of arbitrary (e.g., localized) internal orbitals, and atomic orbitals in the virtual space. The results are strictly equivalent to the canonical formulation if no further approximations are introduced. The new formalism permits the extension of the local correlation method to Møller-Plesset theory. It also facilitates the treatment of weak pairs at a lower (e.g., second order) level of theory in CI and coupled cluster methods. Based on our formalism, an MP2 gradient algorithm is outlined which does not require the storage of derivative integrals, integrals with three external MO indices, and, using the method of Handy and Schaefer, the repeated solution of the coupled-perturbed SCF equations.     

The molecular structure of the complex trimethylaluminium dimethyl ether, (CH3)3AlO(CH3)2, determined by gas phase electron diffraction

The molecular structure of (CH₃)₃AlO(CH₃)₂ has been determined by gas phase electron diffraction. The main molecular parameters are AlC = 1.973(11), AlO = 2.014(14), OC = 1.436(3) Å, OAlC = 98.7(1.5), AlOC = 122.6 (0.5) and COC = 114.5(1.7)°. The OC bond distance and the COC valence angle are significantly larger than those in free dimethyl ether. The three valencies of the oxygen atom appear to lie in one plane. It is suggested that the planarity of the oxygen atom is due to across-angle repulsion Al?C(O).     

Spectral transformations for deconvolution methods applied on gas chromatography-mass spectrometry data

In hyphenated chromatography, overlapping chromatographic peaks can be resolved into pure spectra and pure chromatographic profiles by several multivariate deconvolution techniques. In general, these methods require bilinearity, which implies that the spectrum of each analyte is constant. The slow scan speeds normally used in gas chromatography-mass spectrometry (GC-MS) will destroy bilinearity and introduce systematic noise in the data because the concentration in the detector changes during the scan. This effect, described as the scan effect, may hinder successful resolution by multivariate deconvolution. In selected ion monitoring (SIM) GC-MS, the scan effect may be removed by simple transformations of the mass spectra. The effects of different transformations are demonstrated both on pure chromatographic peaks and on difficult resolution problems where there are small differences between the spectra of the analytes.     

Microwave spectrum and conformational composition of 3-fluoropropionitrile (FCH2CH2CN)

The microwave spectrum of 3-fluoropropionitrile, FCH(2)CH(2)C≡N, has been investigated in the whole 17-75 GHz spectral region. Selected portions of the spectrum in the 75-95 GHz have also been recorded. The microwave spectra of the ground state as well as of three vibrationally excited states of each of two conformers have been assigned. The spectra of the vibrationally excited states belong to the lowest torsional and bending vibrations. The F-C-C-C chain of atoms is exactly antiperiplanar in one of these rotamers and synclinal in the second conformer. The F-C-C-C dihedral angle is 65(2)° in the synclinal form. The energy difference between the two forms has been obtained from relative intensity measurements performed on microwave transitions. It was found that the antiperiplanar conformer is more stable than the synclinal form by 1.4(5) kJ/mol. It is argued that the gauche effect is a significant force in this compound. Quantum chemical calculations at the high CCSD(full)/cc-pVTZ, MP2(full)/cc-pVTZ, and B3LYP/cc-pVTZ levels of theory have been performed. Most, but not all, of the theoretical predictions are in good agreement with experiment.     

Structures and vibrational spectra for protonated carbonyl sulfide

The HOCS⁺ form of protonated OCS was identified in 1987 using high-resolution difference frequency laser spectroscopy by assigning the vibrational frequency (ν=3435cm⁻¹) as the O-H stretch. The isomer HSCO⁺ was not detected in spite of a search of the S-H stretching region. Theoretical calculations indicate, however, that the S-protonated form lies significantly lower than the O-protonated form. To resolve this apparent discrepancy between experiments and theoretical calculations, highly accurate ab initio studies of both species have been carried out. Our results indicate that the S-protonated form lies about 5 kcal/mol below the O-protonated one. The SH stretching frequency is predicted to be found around 2496cm⁻¹. A new search for the ν₁ band of HSCO⁺ using a diode spectrometer showed no evidence of HSCO⁺. Received: 26 November 1996 / Accepted: 3 March 1997