Robert T. C. Brownlee

Structure of epiglucan, a highly side-chain/branched (1→3;1→6)-β-glucan from the micro fungus Epicoccum nigrum Ehrenb. ex Schlecht

The extracellular fungal polysaccharide, epiglucan, synthesised by Epicoccum nigrum is a side-chain/branched (1 --> 3;1 --> 6)-D-beta-glucan. Methylation analysis, 13C DEPT NMR and specific enzymic digestion data show slight variation in branching frequency among the epiglucans from the three strains examined. The (1 --> 3)-beta-linked backbone has (1 --> 6)-beta-linked branches at frequencies greater than the homologous glucans, scleroglucan and schizophyllan, from Sclerotium spp. and Schizophyllum commune, respectively. The structural analyses do not allow a distinction to be made between structures I and II. [structures: see text] Epiglucan displays non-Newtonian shear thinning rheological properties, typical of these glucans.

The Facile Production of N-Methyl Amino Acids via Oxazolidinones

A range of oxazolidinones derived from N-carbamoyl α-amino acids were prepared by an efficient method as key intermediates in the synthesis of N-methyl amino acids and peptides. The method was readily applied to most α-amino acids except those with basic side chains. The oxazolidinones were converted by reductive cleavage into N-methyl α-amino acids.

Effect of atomic charge, solvation, entropy, and ligand protonation state on MM-PB(GB)SA binding energies of HIV protease

The molecular mechanics‐Poisson‐Boltzmann surface area (MM‐PBSA) and MM‐generalized‐Born surface area (MM‐GBSA) approaches are commonly used in molecular modeling and drug design. Four critical aspects of these approaches have been investigated for their effect on calculated binding energies: (1) the atomic partial charge method used to parameterize the ligand force field, (2) the method used to calculate the solvation free energy, (3) inclusion of entropy estimates, and (4) the protonation state of the ligand. HIV protease has been used as a test case with six structurally different inhibitors covering a broad range of binding strength to assess the effect of these four parameters. Atomic charge methods are demonstrated to effect both the molecular dynamics (MD) simulation and MM‐PB(GB)SA binding energy calculation, with a greater effect on the MD simulation. Coefficients of determination and Spearman rank coefficients were used to quantify the performance of the MM‐PB(GB)SA methods relative to the experimental data. In general, better performance was achieved using (i) atomic charge models that produced smaller mean absolute atomic charges (Gasteiger, HF/STO‐3G and B3LYP/cc‐pVTZ), (ii) the MM‐GBSA approach over MM‐PBSA, while (iii) inclusion of entropy had a slightly positive effect on correlations with experiment. Accurate representation of the ligand protonation state was found to be important. It is demonstrated that these approaches can distinguish ligands according to binding strength, underlining the usefulness of these approaches in computer‐aided drug design.

A theoretical investigation of the π-polarization mechanism. The importance of localized and extended polarization

Ab initio molecular orbital theory has been used to examine the π-polarization mechanism. ‘Isolated molecule’ calculations have been made for the pairs C3HX/H2CCH–HCO, with X being varied through a range of common substituents. The dipole of X is able to polarize the π electrons of the acrolein unit such that both polarization of the entire conjugated system and separate polarization of the individual CC and CO π units occurs. The relative importance of extended and localized polarization varies for different atomic positions within the acrolein probe molecule. At the terminal oxygen atom, extended polarization accounts for ca. 60% of the total polarization whilst for the carbonyl carbon it accounts for only 20%. Most of the polarization at this position arises from localized polarization of the carbonyl unit. These results are in agreement with 13C s.c.s. data in related systems.

Stereochemical course of glucan hydrolysis by barley (1 → 3)- and (1 → 3,1 → 4)-β-glucanases

The stereochemical course of hydrolysis of Laminaria digitata laminarin and barley (1-->3, 1-->4)-beta-glucan by barley (1-->3)-beta-glucanase (E.C. 3.2.1.39) isoenzyme GII and (1-->3, 1-->4)-beta-glucanase (EC 3.2.1.73) isoenzyme EII, respectively, has been determined by 1H-NMR. Both enzymes catalyse hydrolysis with retention of anomeric configuration (e-->e) and may therefore operate via a double displacement mechanism. We predict that all other members of Family 17 of beta-glycosyl hydrolases also follow this stereochemical course of hydrolysis.

The nature of substituent electronic effects; the existence of the π-inductive effect

Measurements of 13C n.m.r. shifts and of u.v and i.r. intensities for ω-substituted alkylbenzenes show the presence of a π-inductive effect. Various possible mechanisms contributing to such effects are analysed and the discussion is extended to related benzyl systems.

Applications of 95Mo NMR spectroscopy. XIII. Relaxation times of molybdenum compounds

Abstract The 95 Mo spin-lattice and spin-spin relaxation times have been measured for a number of compounds with linewidths ranging from less than 1 to 1720 Hz. Corresponding relaxation times range from 7 s to 180 μs. The results indicate that quadrupole relaxation is the only significant mechanism involved, allowing the T 1 values to be interpreted in terms of the electric field gradient, molecular size and shape, solution viscosity, temperature, and solvent-solute interactions. 97 Mo relaxation times are also reported for the more highly symmetric compounds.

Reproducibility of Integrated Infrared Intensity Measurements

Careful control of instrument parameters and the use of a computer program for integration gives a reproducibility of <±2% between intensity measurements of reasonably isolated absorptions on different grating spectrometers in different laboratories.

Applications of 95Mo NMR Spectroscopy. X1. 95Mo 97Mo, and 17O relaxation times, quadrupole coupling constants, and the molybdenum relaxation mechanism in Mo(CO)6

Abstract Spin-lattice relaxation times ( T 1 s) of 95 Mo 97 Mo, 17 O, and 13 C for Mo(CO) 6 in CDCl 3 are reported. The rotational correlation time of the molecule is obtained from the chemical-shift anisotropy relaxation of 13 C. Quadrupole coupling constants are calculated for 95 Mo 97 Mo, and 17 O. The results indicate that 95 Mo and 97 Mo, relaxation is entirely quadrupolar and is caused by rotational reorientation of a permanent quadrupole coupling constant rather than from solvent molecule collisions and vibrationally induced momentary electric field gradients.

Synthesis and phototoxicity of a series of haematoporphyrin analogues

Abstract The synthesis of new haematoporphyrin analogues is described. These porphyrins have been assayed for phototoxicity and cellular localization and show promise for use in photodynaic therapy of cancer.