M.A. Whitehead

Aromatic nitrogen heterocyclic heats of formation: a comparison of semiempirical and ab initio treatments

Abstract Ab initio calculated azole, azine and benzoazole heats of formation are within 0–4 kcal mol −1 of experimental results for isolobal reaction schemes. The ab initio heats of formation are compared with calculated semiempirical (MNDO, AM1 PM3) heats of formation. The MNDO method systematically underestimates all nitrogen heterocyclic heats of formation. The AM1 method overestimates azole and underestimates azine heats of formation. The PM3 method performs well on azoles and benzoazoles, but underestimates azine heats of formation. Overall, the PM3 method is the most accurate semiempirical method for calculating nitrogen heterocyclic heats of formation. Correction terms for the semiempirical azine heats of formation are suggested, which bring semiempirical values into agreement with experimental results. Semiempirical and ab initio methods are used to predict pentazole, pentazine, hexazine, pyrazepine, indazine, purine and azolotriazine heats of formation.

Group orbital electronegativities

The Self-consistent Group Orbital and Bond Electronegativity (SGOBE) method [4] for calculating the orbital charge distributions in polyatomic molecules is reviewed, and a simplification described. The charge distributions for several polyatomic molecules are calculated. The chemical significance of the results is discussed.ZusammenfassungEs wird ein Überblick über die SGOBE-Methode zur Berechnung von Ladungsverteilun-gen in Molekülen gegeben und eine Vereinfachung dazu beschrieben. Die Ladungsverteilung einiger mehratomiger Moleküle wird berechnet und die chemische Bedeutung diskutiert.RésuméLa méthode auto-cohérente des orbitaux de groupe et électronégativités des liaisons (SGOBE) pour calculer la distribution de charge orbitale des atomes dans les molécules poly-atomiques est résumée, et une simplification de la méthode SGOBE est décrite. Les distributions de charge de plusieurs molécules polyatomiques sont calculées, et la signification des résultats est discutée.

Click dendrimers as anti-inflammatory agents: with insights into their binding from molecular modeling studies.

These studies explore the relationship between the inhibitory actions of low generation dendrimers in stimulated microglia and dendrimer-enzyme interactions using in silico molecular modeling. Low generation (DG0 and DG1) dendrimers with acetylene and hydroxyl terminal groups were tested for their anti-inflammatory activity in microglia stimulated by lipopolysaccharides (LPS), and the results were compared with those from the established anti-inflammatory agents, ibuprofen and celecoxib. We hypothesized that hydroxyl terminal groups of DG0 and DG1 dendrimers could interact with the active sites of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes due to their small size and favorable electrochemical properties. The enzymatic activity of iNOS and COX-2 was determined in the presence of low generation dendrimers using biochemical assays and their values related to dendrimer docking confirmations from in silico molecular modeling. We found that results from the molecular modeling studies correlated well with the in vitro biological data, suggesting that, indeed, hydroxyl terminal groups of low generation dendrimers enable multivalent macromolecular interactions, resulting in the inhibition of both iNOS and COX-2 enzymes.

Study of the influence of the non-pyridyl nitrogen hybridisation on the stability of axially chiral analogues of 4-(dimethylamino)pyridine (DMAP)

Abstract This study investigates and explains the differences in rotational energy barriers between two series of atropisomeric biaryl derivatives of DMAP, using computational methods to determine the rotational energy barriers of a large number of compounds. A theoretical investigation of the rotational barriers of an asymmetric nucleophilic catalyst determined the most configurationally stable DMAP analogue. The rotational barriers of DMAP derivatives are from ab initio RHF/STO-3G (for conjugated amines), and semi-empirical PM3 calculations. The enantiomerisation energies are from energy scans around the Ar–Ar bond of each molecule, and are then compared to experiment. The theoretical rotational energies, for each series of DMAP derivatives, show a trend within the series. This allows prediction of the rotational energies for compounds, which have not been determined experimentally. The calculations show that the difference in barriers to rotation, between the series, reflects the difference in hybridisation of the non-pyridyl nitrogen in the transition state structures.

3,5-Dihydroxybenzylalcohol based dendrimers : structure evaluation and molecular encapsulation in generations 1-5

Geometric characterization of 3,5-dihydroxybenzyl alcohol (DHBA)-based dendrimers has been achieved using molecular mechanics MM+ method and the PM3 semi-empirical molecular orbital theory. Optimization of DHBA-based dendrimer generations 1–5 (DG1–5) showed that DG1–3 have a relatively open structure with no internal spaces of any particular size or shape, while DG4 and 5 assume a more globular structure with well-defined internal cavities. Encapsulation of disperse red 1 (DR1) into the cavities of these dimethylsilyl linked DHBA-based dendrimers led to a blue shift in the λmax of DR1, and transmission electron microscopy (TEM) showed a rectangular shape of dendritic aggregates containing DR1. Catalytic activity of (COD)RhCl(PPh2(CH2)3OH) encapsulated in dendritic aggregates below and above critical aggregation concentration (cac) of generations 1–4 was examined. A significant decrease in catalytic conversion of 1-decene to decane in dendrimer generations 4 upon going from a concentration below cac to above cac was observed.

The molecular structure of pentastanna[1.1.1]propellane and bicyclo[1.1.1]pentastannane from the quasi-relativistic SIC-MS-Xα theory

Abstract The electronic structures of pentastanna[1.1.1]propellane and bicyclo[1.1.1]pentastannane were studied with the quasi-relativistic self-interaction-corrected multiple-scattering-Xα method. The bonding between the five tin atoms in both molecules was σ between the bridgehead and π to the three peripheral atoms.

Characterization of a novel self-association of an alternating copolymer into nanotubes in solution

The characterization of the association of an alternating copolymer was performed using theoretical methods (quantum mechanics and molecular mechanics) and experimental methods (cryo-Transmission Electron Microscopy (cryo-TEM), neutron reflectivity and neutron scattering). The most stable conformation obtained for the self-association at pH 7 using theoretical methods is a tubular structure in which eight SMA molecules make one twist of a helix. The tubes can grow in length by continued regular stacking of benzene rings. The nanotubes have inner and outer diameters of about 28 and 41 Å, respectively. The hydrophobic groups are mainly located inside the tube and the hydrophilic groups are mainly on the exterior surface of the tube. They can also associate with themselves creating planes of aligned tubes, which can stack upon each other. The association of alternating copolymers into nanotubes is a novel self-association process. The association of SMA octamers into a tubular structure at pH7 was confirmed experimentally by cryo-TEM and the nanotubes observed were several micrometers long. The shape as well as the inner and outer diameter of the nanotubes were also characterized by neutron scattering and the conformation at the air–water interface by neutron reflectivity.

Semi-empirical study of isocyanate geometries, and β-lactam formation through alkene-isocyanate cyclo-addition reactions

Abstract Semi-empirical and ab initio geometries and energies of ground state isocyanate molecules are compared with experimental values. Semi-empirical methods isocyanate geometries compare well with experimental values. Without polarization, 3-21G, 6-31G, and 6-311G ab initio basis sets all give incorrect linear geometries. Polarization functions improve ab initio isocyanate geometries drastically, to agree with experiment. Semi-empirical calculations (MNDO, AM1 and PM3) of the β-lactam forming isocyanate cycloaddition reaction, with various substituted alkenes, show MNDO and AM1 transition state geometries significantly different from ab initio transition state geometries; PM3 activation energy barriers and transition states are in better agreement with high level ab initio and PM3 is the most accurate semi-empirical method for the hydrogen isocyanate heat-of-formation.

Electronegativity and hardness of molecular groups from the localized electronegativity group orbital (LEGO) and generalized exchange local spin density functional (LSD-GX) theories

Abstract Mulliken electronegativities and Orsky-Whitehead acid-base hardnesses were determined for selected non-quark and quark atoms. The ionization potentials and electron affinities were calculated from statistical total energies calculated using the self-interaction corrected generalized exchange local spin density functional theory with Vosko, Wilks and Nusair correlation energy (LSD-GX-VWN-SIC). There is good agreement with experiment for non-quark atoms; there is moderate agreement for quark atoms compared to quark atom data calculated by alternative methods. The valence state ionization potentials for the sp 3 and sppp valence states were calculated for selected non-quark and quark atoms using the LSD-GX and LSD-GX-VWN-SIC theories, and used to calculate the neutral, acid and base electronegativities and the Orsky-Whitehead acid-base hardnesses for molecular groups. The results show the expected behaviour for the sp 3 valence state for both non-quark and quark atoms and molecular groups. The hard-soft acid-base (HSAB) theory is discussed with respect to the trends observed in the data and is used to predict the correct behaviour in a representative hard-soft acid-base reaction.

A COMPARISON OF SEMIEMPIRICAL AND AB INITIO CALCULATIONS ON DIAZOAZOLES AND AZOLYLIDENES

Abstract Semiempirical (MNDO, AM1, PM3) and ab initio (R/UHF/6-31G∗∗) methods are used to calculate the geometries, energies and heats of formation of a series of diazoazoles and azolylidenes. Unsubstituted azoles, cyclopentadiene, diazocyclopentadiene and aminoazoles are studied for comparison. Ab initio and semiempirical conformational analyses demonstrate the floppy nature of the CNN bond angle. Ring bond lengths in diazoazoles show that bond localization is greater in diazoazole rings than in azole or aminoazole rings. Ab initio atom equivalent diazoazole heats of formation compare well with PM3 semiempirical values. Calculations predict that the triplet spin state is the most stable for all cyclic azolylidenes. All singlet state azolylidenes except 4-triazolylidene are stable high-energy cyclic species. Singlet state 4-triazolylidene is unstable and spontaneously undergoes ring scission to diazoacetonitrile, while triplet state 4-trizaoylidene is stable as a cyclic structure. The results for 4-triazolylidene are used to explain why different products are obtained from thermolysis and photolysis of 4-diazo-1,2,3-diazotriazole.