Craig D. Grimmer

Probing the nature of the Co(III) ion in corrins: the structural and electronic properties of dicyano- and aquacyanocobyrinic acid heptamethyl ester and a stable yellow dicyano- and aquacyanocobyrinic acid heptamethyl ester.

A stable yellow derivative of cobyrinic acid heptamethyl ester, (5R,6R)-Coα,Coβ-dicyano-5,6-dihydro-5-hydroxy-heptamethylcob(III)yrinate-c,6-lactone (DCSYCbs), was prepared from dicyanocobyrinic acid heptamethyl ester (DCCbs). The C5 carbon is oxidized and the c side chain cyclized to form a lactone at C6; the 13 atom, 14 π-e(-) delocalized system of corrins is interrupted, giving a triazamethine system with four conjugated double bonds between N22 and N24 and an isolated double bond between N21 and C4. Stable yellow aquacyanocobyrinic acid heptamethyl ester (ACSYCbs) was prepared by driving off HCN with N(2) in a methanol/acetic acid solution. The electronic spectra of DCCbs and DCSYCbs appear similar except that the bands in DCSYCbs are shifted to shorter wavelengths and the γ-band is much less intense. The experimental spectra were adequately modeled using TD-DFT at the PBE1PBE/6-311G(d,p) level of theory. DCSYCbs crystallizes in the space group P2(1)2(1)2(1) (R(1) = 6.08%) with Z = 4, including one methanol solvent molecule and one water molecule per cobester. The addition of a hydroxyl group at C5 causes loss of the double bond between C5 and C6 and elongation of the C5-C6 bond. From a combination of two-dimensional (1)H TOCSY and ROESY NMR spectra and (1)H/(13)C HSQC and HMBC data, the complete (1)H and (13)C NMR assignments of DCSYCbs were possible, except for two of the ester methyl groups and the (13)C resonances of the two axial cyanide ligands. The latter were assigned using relative chemical shifts calculated by GIAO-DFT methods. The (59)Co resonance of DCCbs was observed at 4074 ppm while that of DCSYCbs is shifted downfield to 4298 ppm. Comparison with available (59)Co data of analogous systems suggests that the more π-conjugated corrin of DCCbs interacts more strongly with the metal than the less extensively conjugated macrocycle of DCSYCbs. As the strength of the interaction between Co(III) and an equatorial macrocycle increases, ν(CN) of axially coordinated CN(-) shifts to lower frequency; in DCSYCbs and DCCbs ν(CN) occurs at 2138 and 2123 cm(-1), respectively. Hence the corrin ligand in DCCbs interacts more strongly with the metal than the stable yellow corrin ligand, with its diminished conjugation. The UV-vis spectral data and DFT-calculated MOs are consistent with greater overlap between the corrin and the metal orbitals in DCCbs relative to DCSYCbs, which gives the metal in the former a softer, more covalent character.

Antiviral atropisomers: conformational energy surfaces by NMR for host-directed myxovirus blockers.

Biologically active organic molecules characterized by a high single bond torsional barrier generate isolable isomers (atropisomers) and offer a unique stereochemical component to the design of selective therapeutic agents. The present work presents a nanomolar active inhibitor of myxoviruses, which most likely acts by blocking one or more cellular host proteins but also, serendipitously, exhibits axial chirality with an energy barrier of ΔG((++)) ≥30 kcal/mol. The latter has been probed by variable temperature NMR and microwave irradiation and by high level DFT transition state analysis and force field calculations. Full conformational profiles of the corresponding (aR,S) and (aS,S) atropisomers at ambient temperature were derived by conformer deconvolution with NAMFIS (NMR Analysis by Molecular Flexibility In Solution) methodology to generate seven and eight individual conformations, each assigned a % population. An accurate evaluation of a key torsion angle at the center of the molecules associated with a (3)JC-S-C-H coupling constant was obtained by mapping the S-C bond rotation with the MPW1PW91/6-31G-d,p DFT method followed by fitting the resulting dihedral angles and J-values to a Karplus expression. Accordingly, we have developed a complete conformational profile of diastereomeric atropisomers consistent with both high and low rotational barriers. We expect this assessment to assist the rationalization of the selectivity of the two (aR,S) and (aS,S) forms against host proteins, while offering insights into their divergent toxicity behavior.

Conformational analysis: 3JHCOC and 3JHCCC Karplus relationships for methylene 1H nuclei

NAMFIS (NMR Analysis of Molecular Flexibility In Solution) was applied to 1‐[2‐(benzyloxy)phenyl]ethanone using quantitative 1H‐1H NOE distances and 3J proton‐carbon coupling constant (CC) restraints for averaged methylene proton 3JHCOC and 3JHCCC pathways H2‐3J‐X imposed by density functional theory‐generated Karplus relationships. Comparison of the NOE‐only versus the NOE + CC conformational selections illustrates that the experimentally measured average 3J coupling constants of methylene protons can be used for solution conformational analysis, potentially valuable in the study of small‐molecule drugs and natural products which lack the typically studied H1‐3J‐X Karplus relationships. Copyright

2-Phenyl-naphtho-[1,8-de][1,3,2]diaza-borinane.

The title compound, C16H13BN2, is one compound in a series of diazaborinanes featuring substitution at the 1, 2 and 3 positions in the nitrogen–boron heterocycle. The title compound is slightly distorted from planarity, with a dihedral angle of 9.0 (5)° between the mean planes of the naphthalene system and the benzene ring. The m-carbon atom of the benzene ring exhibits the greatest deviation of 0.164 (2) Å from the 19-atom mean plane defined by all non-H atoms. The two N—B—C—C torsion angles are 6.0 (3) and 5.6 (3)°. In the crystal, molecules are linked by π–π interactions into columns, with a distance of 3.92 (3) Å between the naphthalene ring centroids. Adjacent π-stacked columns, co-linear with the b-axis, are linked by C—H⋯π interactions.

Crystal structure of 1-[2-(benzyloxy)phenyl]ethanone, C15H14O2

Abstract C15H14O2, monoclinic, P21/c (no. 14), a = 10.664(2) Å, b = 14.406(3) Å, c = 7.686(1) Å, β = 94.260(3)°, V = 1177.6 Å3, Z = 4, Rgt(F) = 0.0417, wRref(F2) = 0.1036, T = 103 K.

Conformational analysis:3JHCOCand3JHCCCKarplus relationships for methylene1H nuclei: 3JHCOCand3JHCCCrelationships for methylene1H nuclei

NAMFIS (NMR Analysis of Molecular Flexibility In Solution) was applied to 1‐[2‐(benzyloxy)phenyl]ethanone using quantitative 1H‐1H NOE distances and 3J proton‐carbon coupling constant (CC) restraints for averaged methylene proton 3JHCOC and 3JHCCC pathways H2‐3J‐X imposed by density functional theory‐generated Karplus relationships. Comparison of the NOE‐only versus the NOE + CC conformational selections illustrates that the experimentally measured average 3J coupling constants of methylene protons can be used for solution conformational analysis, potentially valuable in the study of small‐molecule drugs and natural products which lack the typically studied H1‐3J‐X Karplus relationships. Copyright

1,2-Bis[(2,2′:6′,2′′-terpyridin-4′-yl)­oxy]ethane

The title compound, C32H24N6O2, has an inversion centre located at the mid-point of the central C—C bond of the diether bridging unit. The terminal pyridine rings are canted relative to the central pyridine ring, with dihedral angles of 12.98 (6) and 26.80 (6)°. The maximum deviation from the eight-atom mean plane, defined by the two bridging O and C atoms and the central pyridine ring, is 0.0383 (10)° for the N atom.

Ethyl (2E)-2-(hydroxy­imino)propanoate

The molecule of the title compound, C5H9NO3, is essentially planar [the maximum deviation for a non-H atom from the mean plane is 0.021 (3) Å] due to the π-conjugation of the hydroxyimino and carbonyl groups, which are trans to each other; ab initio calculations in vacuo at the DFT (B3LYP/6–311G**++) level of theory confirmed that E conformer is indeed the lowest in energy. The packing in crystal structure is influenced by strong intermolecular O—H⋯N hydrogen-bonding interactions between oxime groups and also by π-stacking of the molecules due to the carbonyl and oxime group orbital overlap [interplanar distance between adjacent molecules = 3.143 (4) Å]. Jointly, these factors afford infinite 6.32 Å thick molecular sheets, where the plane of each molecule is perpendicular to the plane of the sheet. Seen from above, the molecules within the sheet are arranged in a herringbone pattern. Such sheets form a stack due to weak van der Waals interactions; the gap between adjacent sheets is 2.07 Å.