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The conformational energy map for the rotamers of dimethoxymethane has been calculated using both the 3-21G and 6-31G* basis sets with complete geometry optimization in each case. Higher level calculations including electron correlation also have been performed on selected rotamers. At larger torsional angles, the map has approximate 4-fold symmetry, and this symmetry may be used to quantify the difference in the interactions in the (+sc, {minus}sc) and (+sc, +sc) regions. Large changes in bond angles were found, and the dipole moment also changed considerably on C-O bond rotation. Calculations on equatorial and axial 2-methoxytetrahydropyran show that the axial form is favored by 1.33 kcal/mol, in fair agreement with experiment. Calculations also were carried out on the two lowest energy forms of 1,1-dimethoxyethane and on five forms of methyl propyl ether. Consideration of all these data indicates that the anomeric stabilization in dimethoxymethane is much greater than in sterically more congested systems, but the stabilization of 1,1-dimethoxyethane is similar to that of 2-methoxytetrahydropyran and other acetals.

The rotational barrier about the C-C bond of 1,2-dichloroethane has been calculated by using several basis sets (4-31G, 6-31G*, 6-31+G*, and 6-31++G**) and including electron correlation. Corrections for zero-point energy differences, and the differences in enthalpy change from 0 to 298 K, were made by using the calculated geometries and vibrational frequencies. The trans/gauche energy difference was found to be 1.39 kcal/mol as compared to the observed value, 1.1 +/- 0.1 kcal/mol. The intramolecular interactions in the several rotamers are discussed. The trans/gauche energy difference for 1,2-difluoroethane also was calculated (MP3/6-311++G**) and was found to be 0.76 kcal/mol favoring the gauche conformer, again in good agreement with the experimental value of 0.57 +/- 0.09 kcal/mol. The trend in trans/gauche energy differences in the series n-butane, 1,2-dichloroethane, 1,2-difluoroethane is noted.

Enthalpies de reaction de cyclopentene, cyclohexene, methyl-1 cyclopentene, methylenecyclopentane, methyl-1 cyclohexene, methylenecyclohexane, bicyclo [2.2.1] heptene-2 et bicyclo [2.2.1] hexene-2 avec l'acide trifluoracetique

The bulk of aqueous humor entering the eye is produced through an active secretory process by the nonpigmented epithelial cells of the ciliary process. Carbonic anhydrase is present in these cells, and following inhibition of the enzyme, bicarbonate formation is decreased, which, in turn, diminishes sodium and fluid secretion into the eye. The biological profile of the thienothiopyrans was assessed through in vitro, ex vivo, and in vivo studies. In vitro determination of I 50 and K i values utilized HCA-II, the isozyme found in the human ciliary process

The hydrogen-hydrogen nonbonded potential which may be derived from the calculated interactions between hydrogen molecules has been obtained. The best three-parameter Buckingham function gave an RMS error of 0.18 kcal/mol in fitting Price and Stone's ab initio data for 130 pairs of hydrogen molecules, which may be compared with an RMS error of 0.74 kcal/mol using the parameters in the MM2 force field. Burton's basis set is also considered. A better fit to these data requires that the angular relationship between the bonds be included. The data for hydrogen as well as experimental data for chlorine show that these atoms appear “larger” normal to the bond axis than along the axis, and this is probably also the case for other atoms. When simple angular terms are added it is possible to fit the Price and Stone data set with an RMS error of less than 0.06 kcal/mol. The preferred function was: V = [a0 + a1(sin θ1 + sin θ2)4 + a2r]e−3r − [c0 + c1(1 + sinθ1sinθ2)]/r5. Deficiencies in the current ab initio data are discussed.

The geometries of the lowest energy gauche and trans conformers of 2-fluoroethanol (2FE) and 2-chloroethanol (2CE) have been calculated at the 6-31G* level, and the energies calculated with several basis sets and the inclusion of electron correlation. The global minimum for both compounds is found to be the gauche conformer, in agreement with experiment. At the MP3/6-31G* level, trans 2CE is 1.66 kcal mol−1 higher in energy than gauche, while trans 2FE is 2.34 kcal mol−1 higher than gauche. Geometries were also optimized for various fixed values of the HOCC dihedral angle, from which the barrier to OH rotation was derived. Further calculations at the MP3/6-311+ +G** level lowered the relative energy of trans 2FE by only 0.3 kcal mol−1 to 2.03, but had a much larger effect on the HOCC rotational barrier. Calculations at the MP3/6-311++G** level were also done for ethanol, and a comparison of the ethanol and 2FE rotational profiles indicates a strongly attractive HF interaction which, after elimination of non-bonding and bending contributions, may be most simply modelled as a coulombic term. Vibrational frequencies were estimated for 2FE and 2CE at the 6-31G* level, and do not support the idea that a small HF separation is responsible for the frequency differences between trans and gauche.

Electronegative atoms are expected to prefer to be bonded to orbitals with relatively high p-character. However, observed bond angles are frequently not in accord with this expectation. It is shown that bent bonds are a common occurrence and that the angles between the bond paths are in good accord with common hybridization arguments.

The optimized geometries for the rotamers of propanal, 2-butanone, isobutyraldehyde, methyl isopropyl ketone, and isobutyric acid obtained using the 3–21G and 6–31G* basis sets are compared, and systematic changes are noted. The relative 6–31G* energies using the 3–21G and 6–31G* geometries are generally the same within 0.1 kcal/mol. The effect of electron correlation on the relative energies is generally small. These and related data show that 6–31G* relative energies obtained using 3–21G geometries are generally satisfactory when studying rotation about CC bonds. However, this is not the case for CO bonds. The calculated relative energies of isomeric compounds are reproduced only with the full MP4 correction for electron correlation.

The structure of inosine-5′-monophosphate dehydrogenase (IMPDH) in complex with IMP and mycophenolic acid (MPA) has been determined by X-ray diffraction. IMPDH plays a central role in B and T lymphocyte replication. MPA is a potent IMPDH inhibitor and the active metabolite of an immunosuppressive drug recently approved for the treatment of allograft rejection. IMPDH comprises two domains: a core domain, which is an α/β barrel and contains the active site, and a flanking domain. The complex, in combination with mutagenesis and kinetic data, provides a structural basis for understanding the mechanism of IMPDH activity and indicates that MPA inhibits IMPDH by acting as a replacement for the nicotinamide portion of the nicotinamide adenine dinucleotide cofactor and a catalytic water molecule.

Evidence is presented that indicates a deep crevice located on the surface of human rhinovirus type 14 is involved in virion attachment to cellular receptors. By using mutagenesis of an infectious cDNA clone, 11 mutants were created by single amino acid substitutions or insertions at positions 103, 155, 220, 223, and 273 of the structural protein VP1. Seven of the recovered mutants had a small plaque phenotype and exhibited binding affinities significantly lower than wild-type virus. One mutant, in which glycine replaced proline at amino acid position 155, showed a greatly enhanced binding affinity. Single-cycle growth kinetics suggested that 5 of the mutants had delayed growth cycles due to intracellular deficiencies apart from receptor binding.