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The synthesis and characterization of 1,4-difluorobenzo[c]phenanthrene (1,4-DFBcPh) was carried to understand its extent of DNA binding by the metabolities of dihydrodiol and diol epoxides. The findings showed that increased molecular distortion decreased metabolic activation to the terminal metabolities and the formation of diol epoxide metabolites was the DNA-damaging species.

Time-of-flight neutron diffraction has been used to locate hydrogen atoms that define the ionization states of amino acids in crystals of D-xylose isomerase. This enzyme, from Streptomyces rubiginosus, is one of the largest enzymes studied to date at high resolution (1.8 [Angstrom]) by this method. We have determined the position and orientation of a metal ion-bound water molecule that is located in the active site of the enzyme; this water has been thought to be involved in the isomerization step in which D-xylose is converted to D-xylulose of D-glucose to D-fructose. It is shown to be water (rather than a hydroxyl group) under the conditions of measurement (pH 8.0). Our analyses also reveal that one lysine probably has an -N[H.sub.2]-terminal group (rather than N[[H.sup.+.sub.3]). The ionization state of each histidine residue also was determined. High-resolution x-ray studies (at 0.94 [Angstrom]) indicate disorder in some side chains when a truncated substrate is bound and suggest how some side chains might more during catalysis. This combination of time-of-flight neutron diffraction and x-ray diffraction can contribute greatly to the elucidation of enzyme mechanisms. amino acid ionization states | enzyme mechanism I x-ray diffraction I deuterium/hydrogen in proteins I proton transfer

Methyl group-induced helicity was studied in 1,4-dimethylbenzo(c)phenanthrene and its metabolites.

Distinct aims and goals in crystal engineering are discerned as strategic and methodological, aesthetically motivated supramolecular synthesis and efforts towards functional materials. The polar molecule-based crystal engineering of nonlinear optics (NLO) materials aims to establish the noncentrosymmetric assembly of molecular dipoles. The crystal structures and NLO properties of 2,4,6-triaryloxy-1,3,5-triazines are reported.

A comparison of the crystal structures of a 11-trifluoromethyl derivative of cyclopenta(a)phenanthrene-17-one, 11-methyl- and unsubstituted analogs reveals the importance of C-F...H-C interactions. Substitution at the 11 position increases the twist of the entire molecule. The twist is significant between rings B and C. Analysis of the crystal structures of trifluoro derivatives by graph-set studies reveal the existence of a three-dimensional network of C-H... O double bond C and C-H..F-C interactions. The linearity of these interactions influences alignment of these molecules in the crystals.

X-ray crystallographic studies conducted on the liver alcohol dehydrogenase-bound thiazole-4-carboxamide adenine dinucleotide (TAD) and SAD analogues, beta-TAD and beta-SAD, reveal that both analogues preserve S/Se-O4 interaction. Both analogues are phosphodiesterase-resistant and do not catalyze enzymic movement from the open to the closed end. Beta-TAD and -SAD partially reproduce NAD binding.

The time-of-flight neutron Laue technique was used to determine the location of hydrogen atoms in the enzyme D-xylose isomerase (XI). The linear sugar substrate (xylose or glucose) is extended after the ring-opening stage involved the His54-Asp57 pair and tethered at either end by an H-bond from Lys183 and by an interaction with His54 to O5.

X-ray crystallography, electronic absorption and mass spectroscopy were used to synthesize and characterize difluoromethylcobalamin, a novel vitamin B12 derivative. The crystal structure of the compound revealed a short contact between one of the fluorine atoms and the oxygen atom in side chain c. The compound crystallized with 17 water molecules per formula unit. In addition, the intermolecular interactions involving the solvent molecules and the amide groups were investigated.

The three-dimensional structure of a dihydrodiol epoxide of 5,6-dimethylchrysene was elucidated by X-ray diffraction techniques. The effects of the steric overcrowding by the 5-methyl group in the bay region of this compound are described. The carbon atom of the 5-methyl group is found to lie out of the plane of the aromatic system, thereby avoiding the nearer C-H group of the epoxide ring; this C-H hydrogen atom is pushed in the opposite direction. As a result, the molecule is distorted so that the relative orientations of the epoxide group and the aromatic ring systems are very different for the diol epoxides of (nearly planar) benzo[a]pyrene (studied by Neidle and co-workers) and (distorted) 5,6-dimethylchrysene (described here). The main effect of the 5-methyl group is to change the relative angle between the epoxide-bearing ring (the site of attack when the diol epoxide acts as an alkylating agent) and the aromatic ring system (which is presumed to lie partially between the DNA bases in the DNA adduct that is about to be formed). This may favor some specific alkylation geometry. [ABSTRACT FROM PUBLISHER]

The crystal structure of a novel nucleoside isolated from guanosine/-methylbenzyl chloride reactions demonstrates linkage between the methylene carbon of the benzyl moiety and carbon-5 of guanosine, and loss of the carbonyl function at carbon-6 of guanosine, to yield 4-(-methylbenzyl)-5-guanidino-1-β-D-ribofuranosylimidazole. These findings suggest that carbon-5 of guanine in DNA is a potential site of reaction for electrophilic ultimate carcinogens. [ABSTRACT FROM PUBLISHER]