A new class of intramolecularly hydrogen-bonded dendrons based on a 2-methoxyisophthalamide repeat unit.

The synthesis and conformational properties of folded dendrons based on a 2-methoxyisophthalamide (2-OMe-IPA) repeat unit are described. The hydrodynamic properties of dendrons preorganized via the syn-syn conformational preference of 2-methoxyisophthalamide are compared with 2,6-pyridinedicarboxamide (2,6-pydic) analogues. The effect of subtle differences in the nature of the conformational equilibria that exist within the 2-OMe-IPA and 2,6-pydic repeat units on the global structural properties of the corresponding dendrons was explored computationally, by (1)H-DOSY NMR spectroscopy and time-resolved fluorescence anisotropy (TRFA) measurements. Whereas the syn-syn preference of the 2-OMe-IPA branched repeat unit is stabilized entirely by intramolecular hydrogen-bonding interactions, this preference in the 2,6-pydic system is a consequence of both intramolecular hydrogen-bonding and dipole minimization effects. However, nonspecific solvophobic compression is more important in determining hydrodynamic properties than solvent-dependent shifts in the conformational equilibria of the repeat unit for both dendron series.

Conformational analysis of methyl 5-O-methyl septanosides: effect of glycosylation on conformer populations.

Methyl 5-O-methyl-alpha-d-glycero-d-idoseptanoside (3) and methyl 5-O-methyl-beta-d-glycero-d-guloseptanoside (4) were investigated as (1-->5)-linked di-/oligoseptanoside mimetics. Here we report the synthesis of 3 and 4 and describe their preferred solution conformations through a combination of ab initio/DFT calculations and (1)H (3)J(H,H) NMR coupling constant analysis. The conformations of 3 and 4 observed in this study are discussed in comparison to those of the parent (C5 hydroxy) compounds 1 and 2. The results indicate that methyl 5-O-methyl-alpha-septanoside 3 is relatively rigid and adopts the same (3,4)TC(5,6) conformation as 1. Methyl 5-O-methyl-beta-septanoside 4 is somewhat less rigid than its parent septanoside (2). In addition to the (6,O)TC(4,5) conformation adopted by 2, beta-septanoside 4 also populates the adjacent (3,4)TC(5,6) conformation. Glycosylation at C5 on beta-septanoside 4 therefore increases its overall flexibility and allows access to alternative ring conformations.

On the electrophilicity of hydroxyl radical: a laser flash photolysis and computational study.

The rate coefficients for reactions of hydroxyl radical with aromatic hydrocarbons were measured in acetonitrile using a novel laser flash photolysis method. Comparison of kinetic data obtained in acetonitrile with those obtained in aqueous solution demonstrates an unexpected solvent effect on the reactivity of hydroxyl radical. In particular, reactions of hydroxyl radical with benzene were faster in water than in acetonitrile, and by a significant factor of 65. Computational studies, at the B3LYP and CBS-QB3 levels, have confirmed the rate enhancement of hydroxyl radical addition to benzene via calculation of the transition states in the presence of explicit solvent molecules as well as a continuum dielectric field. The origin of the rate enhancement lies entirely in the structures of the transition states and not in the pre-reactive complexes. The calculations reveal that the hydroxyl radical moiety becomes more anionic in the transition state and, therefore, looks more like hydroxide anion. In the transition states, solvation of the incipient hydroxide anion is more effective with water than with acetonitrile and provides the strong energetic advantage for a polar solvent capable of hydrogen bonding. At the same time, the aromatic unit looks more like the radical cation in the transition state. The commonly held view that hydroxyl radical is electrophilic in its reactions with DNA bases is, therefore, strongly dependent on the ability of the organic substrate to stabilize the resulting radical cation.

The gas-phase acidity of 2(3H)-oxepinone: a step toward an experimental heat of formation for the 2-oxepinoxy radical.

In an effort to gain further insight into the oxidation of the phenyl radical, this contribution details the first of three experiments designed to establish the heat of formation of the 2-oxepinoxy radical. We report here the synthesis of the previously unknown 2(7H)-oxepinone (12a) and 2(3H)-oxepinone (12b). We have determined the gas-phase acidity (Delta(acid)H(298)) of 12b by means of a bracketing study employing a flowing afterglow apparatus with quadrupole mass spectrometric detection. In this experiment, compound 12b was reacted in the gas phase with a series of bases of varying strength. A proton-transfer reaction was observed when 12b was reacted with t-BuS(-), but not when 12b was reacted with HS(-). We conclude that the gas-phase acidity of 12b lies between those of t-BuSH and H(2)S, and it is thereby assigned a value of Delta(acid)H(298) = 352 +/- 2 kcal/mol. Additional support for this value was found by performing the reverse reactions (i.e. the 2-oxepinoxy anion (15a) was reacted with proton sources of differing acidities). Anion 15a underwent a proton-transfer reaction with H(2)S but not with t-BuSH, in agreement with the results from the forward reactions. The experimental value of the gas-phase acidity agrees well with those from DFT calculations, which predicted Delta(acid)H(298) = 348.9 kcal/mol at the B3LYP/6-31+G(d) level and 349.2 kcal/mol at the B3LYP/aug-cc-pVTZ level.

Septanose carbohydrates: synthesis and conformational studies of methyl alpha-D-glycero-D-idoseptanoside and methyl beta-D-glycero-D-guloseptanoside.

We report the synthesis of methyl alpha-D-glycero-D-idoseptanoside (1) and methyl beta-D-glycero-D-guloseptanoside (2) and the characterization of their preferred solution conformations by computational chemistry and (1)H NMR (3)J(H,H) coupling constant analysis. Central to the synthetic approach was the epoxidation of glucose-derived oxepine 3 using DMDO. Nucleophilic attack on the resulting 1,2-anhydroseptanose using NaOCH(3) in CH(3)OH followed by deprotection provided the 1,2-trans diastereomers 1 and 2. The computational approach for determining the preferred low energy septanose conformations began with a pseudo Monte Carlo search for each isomer using minimization with the AMBER force field. Single-point energy calculations (HF/6-31G *and B3LYP/6-31+G**) as well as full geometry optimizations in a model for aqueous solvent were then conducted using the conformers within 5 kcal/mol of the AMBER global minimum. Calculated (3)J(H,H) values, based on a Boltzmann distribution of the computed low energy conformers, were compared to experimental (3)J(H,H) values from (1)H NMR coupling constant analyses. The correlation between calculated and observed values suggest that septanose carbohydrates are not so flexible and should generally prefer one twist-chair (TC) conformation.