摘要:

The carcinogens 4-aminobiphenyl and 2-aminofluorene are metabolized to hydroxylamine esters that undergo N-O heterolysis to produce arylnitrenium ions that react with DNA, especially at guanine residues. These nitrenium ions and a number of their derivatives have been studied by the laser flash photolysis technique, to provide direct kinetic information about the lifetimes of the electrophiles in water and their reactivities with added nucleophiles. Arylnitrenium ions ArNH+are longer-lived in water than arylcarbenium analogs ArCH2+, in some cases significantly longer-lived. The nitrenium ions do react with azide ion at the diffusion limit (providing the cation is not highly stabilized). This behaviour completely parallels that of carbenium ions. The biphenylyl- and fluorenylnitrenium ions react with guanine derivatives such as 2-deoxyguanosine (dG) with rate constants that are close to or at the diffusion limit (2 × 109M-1s-1) for the more reactive cations. Thus, in spite of cation lifetimes of the order of 100 ns to a millisecond in water, dG effectively competes with the solvent. The product is a C8 adduct, the same adduct observed with carcinogenic arylamines and DNA. With delocalized carbenium ions that have similar lifetimes, guanine derivatives compete very poorly with water. Thus, arylnitrenium ions have high dG:water selectivities; arylcarbenium ions have low selectivities. Nitrenium ions and carbenium ions do have parallel reactivities with primary alkyl amines. More reactive cations show a greater reactivity with less basic amines and the rate constants level below the diffusion limit. This can be explained by hydrogen bonding of the amine lone pair. Using the NH2group of the alkyl amines as a model for the C2-NH2group of guanine shows why nitrenium ions show no detectable reactivity at this site. The rate constant for the nitrenium-guanine reaction that forms the C8 adduct is at least an order of magnitude greater than that of a nitrenium-NH2reaction. Nitrenium ions do form a guanine-NH2adduct in DNA, suggesting that incorporation into the polymer changes reactivity patterns. With imidazoles, nitrenium ions show reactivity trends that parallel the nitrenium-dG reaction, with rate constants levelling at the 2 × 109limit for the more reactive cations. Imidazole itself and 1-methylimidazole are generally less reactive than dG, while 2-methylimidazole and 1,2-dimethylimidazole are very similar. A Brönsted-like plot incorporating points for dG, primary amines and imidazoles shows no correlation of nitrenium rate constants with nitrogen basicity. This is true even if only dG and imidazoles are considered. Thus a previous correlation of nitrenium reactivity with purine N7 basicity is suspect. The conclusion is that there is some feature of guanine that makes its reaction with nitrenium ions unusually fast. The reasons for this are not immediately apparent, especially since there is conflicting evidence as to the detailed nature of the mechanism of the reaction that forms the C8 adduct.Key words: nitrenium, aryl azide, guanine, DNA, carcinog

ISSN:0008-4042    

DOI:10.1139/v98-187

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

The synthesis of optically active &agr;-alkoxymethyl benzyl alcohols by reaction of polysubstituted benzaldehydes with chiral &agr;-alkoxymethyllithiums, easily obtained by transmetallation of the corresponding &agr;-alkoxystannanes withn-butyllithium, is reported. Chemical yields of the transformation are good while low asymmetric induction (<1.6:1) is obtained.Key words: diastereoselective synthesis, monoprotected glycols, chiral alkoxymethyllithiums, addition to aldehydes, optically active alcohols.

ISSN:0008-4042    

DOI:10.1139/v98-193

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

&agr;-Lithiated benzylphosphonate esters, XC6H4CH(Li)PO3Et2, add regioselectively to cyclohex-2-enone at the carbonyl group; higher reaction temperatures lead to the reversal to the starting materials, and not to the 1,4-addition. Relative configuration of the C(1) and C&agr;centers in the 1,2-adducts was determined from the13C NMR spectra. For 2-methylcyclohex-2-enone the regioselectivity of the addition is decreased. The lithioderivative of diethyl 1-naphthylmethylphosphonate, C10H7CH(Li)PO3Et2, shows reverse regioselectivity yielding the 1,4-, but not the 1,2- addition product. The crystal and molecular structure of that 1,4-adduct has been determined and demonstrates that the conformation about the C(1)-C&agr;bond is close to that existing in solution, deduced from the value of the1H NMR3JHHvicinal coupling constant of the H(1)-C(1)-C&agr;-H hydrogens. The same conformation was also confirmed as the most stable by molecular modeling.Key words: &agr;-lithiated arylmethylphosphonates, 1,2- vs. 1,4-addition to cyclic enones, steric effects of the cyclohex-2-enone, molecular structure and molecular modelling of the 1,4-adduct of 1-naphthylmethylphosphonate to cyclohex-2-enone.

ISSN:0008-4042    

DOI:10.1139/v98-180

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

Three boronates have been synthesized by reaction of tridentate azomethine ligands derived from salicylaldehyde with phenylboronic acid. The [5.4.0], [4.4.0], and [4.3.0]heterobicyclic structures obtained have been characterized by NMR spectroscopy and X-ray crystallography, whereby it could be proved that the [4.4.0]heterobicycle is the most stable one. Unexpectedly the salicylideneaminoethanol derivative does not lead to a macrocyclic structure, although molecular modeling reveals high ring strain for the monomeric product that is actually obtained.Key words: boronates, boron complexes, tridentate azomethine ligands, phenylboronic acid, X-ray crystallography.

ISSN:0008-4042    

DOI:10.1139/v98-181

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

Monophase binary iron-manganese spinel oxides of high dispersity are prepared by thermal decomposition of carbonate precursors in the limits 0.33<Fe/Mn<2, at temperatures 570-770 K. Interparticlemeso- and macropores contribute to the surface morphology of the spinel oxides, composed from spherical-shaped particles with diameters in the range 7-12 nm. The cation distribution of manganese ferrite corresponds to Mn0.85Fe0.15[Mn0.14Fe1.86]O4+&dgr;. Surface analysis by ESCA reveals high concentration of nonstoichiometric oxygen and presence of Mn(III) and Mn(IV) is indicated in the X-ray photoelectron spectra. Reduction with hydrogen proceeds in two steps and is shifted to higher temperatures with increasing the iron content.Key words: ferrite, spinel, Fe, Mn.

ISSN:0008-4042    

DOI:10.1139/v98-186

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

Oxanorbornane (7-oxabicyclo[2.2.1]heptane, C6H10O) resembles other bicycloheptane-like molecules by exhibiting order-disorder transitions in the solid state. Differential scanning calorimetric studies show that five different phases may occur, with hysteresis in the transition temperatures. The vibrational spectra have been examined, and a factor group analysis of the vibrational splittings indicates that the crystal structure of the ordered phase hasD2dsymmetry. Activation energies for molecular motions were derived from proton spin-lattice relaxation time measurements.Key words: oxanorbornane, order-disorder, phase transitions.

ISSN:0008-4042    

DOI:10.1139/v98-173

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

The crystal structure of unsymmetrical azine 4-aminoacetophenone (1-(4-fluorophenyl)ethylidene)hydrazone hydrate,1·H2O, was determined. Comparison to the X-ray structures of the symmetrical 4-fluoro- and 4-aminoacetophenone azines,2and3, respectively, reinforces the view of the azine bridge as a conjugation stopper. The focus of the analysis lies with the supramolecular architecture. The structure demonstrates azines as double T-contact synthons and suggests that novel L-type arene-arene contacts also might play a significant role in the supramolecular architecture. The absence of inter-water hydrogen bonding in an extremely low-density water layer is one of the surprising and unique features of the solid-state structure of the title compound. The water layers connect azine layers through a hydrogen bonded network which is described by graph set analysis.Key words: arene-arene interaction, hydrogen bonding, graph set analysis, azine, supramolecular synthon, low density water monolayer.

ISSN:0008-4042    

DOI:10.1139/v98-171

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

[Ru(II)(L)6]2+complexes were synthesized from [Ru(DMF)6][CF3SO3]3; DMF = dimethylformamide, L = imidazole (Im),N-methylimidazole (NMeIm) and 5-methylimidazole (5MeIm). The 2-methylimidazole complextrans-[Ru(CO)(DMF)(2MeIm)4][CF3SO3]2(4) was also synthesized via a reaction involving abstraction of CO from DMF;4loses CO reversibly at ambient temperature to form [Ru(DMF)(2MeIm)4][CF3SO3]2(5), and the DMF can be removed to generate a [Ru(CF3SO3)x(2MeIm)4][CF3SO3]yspecies (x= 2,y= 0, orx= 1 =y), containing coordinated triflate. The complexes were characterized by elemental analysis, conductivity, UV-vis, NMR, and IR spectroscopies. The structures of [Ru(Im)6][CF3SO3]2(1), [Ru(NMeIm)6][CF3SO3]2(2), and [Ru(5MeIm)6][CF3SO3]2(3) were established by X-ray crystallographic analyses. Crystals of1, are triclinic,a= 7.4010(6),b= 9.9846(15),c= 11.275(2) Å, &agr; = 113.469(5), &bgr; = 92.419(2), &ggr; = 94.737(2)°,Z= 1, space groupP1 ; those of2, are trigonal,a= 11.558(2),c= 8.109(3) Å,Z= 1, space groupP3; and those of3, are trigonal,a= 12.6547(4),c= 20.4078(12) Å,Z= 3, space groupR3. The structures were solved by Patterson methods and refined by full-matrix least-squares procedures toR(F) = 0.029, 0.034, and 0.034 (Rw(F2) = 0.055,Rw(F) = 0.031, andRw(F2) = 0.058), respectively.Key words: hexakis(imidazole)ruthenium(II) triflates, crystal structures, CO abstract

ISSN:0008-4042    

DOI:10.1139/v98-177

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

Using computer simulations, a geometry for the receptor binding site for nerve growth factor (NGF) has been proposed. Variable basis Monte Carlo simulated annealing calculations have been used to ascertain the structures of the complexes of four fully active NGF analogues with the second leucine-rich motif (LRM-2) of trkA, a putative binding site for NGF. The previously suggested bioactive conformation of the amino and carboxyl termini of NGF docks favourably with the receptor defined by the LRM-2 of trkA: only minor conformational changes take place in the NGF analogues upon docking. Extensive intermolecular van der Waals contacts arise from the geometric fit of the NGF binding domain to the LRM-2. Within this receptor environment, five distinct binding areas reveal a highly selective multiple-point NGF-trkA recognition based on hydrophobic, ionic, hydrogen bonding, and van der Waals interactions. Binding specificity is determined primarily by residues Lys100, Asp109, and Phe113of trkA which bind to conserved NGF residues Asp16, Arg114, Lys115, and Phe7. An explicit atom-level model of the high-affinity NGF receptor is thus developed.Key words: NGF, trkA, leucine-rich motif, protein docking, Alzheimer's disease.

ISSN:0008-4042    

DOI:10.1139/v98-183

出版商:NRC Research Press    

年代:1998

数据来源: NRC

摘要:

Many proteins undergo a phase change whereby catalytic activity is switched on at a glass-transition temperatureT* ~ 200 K. OverT*, large anharmonic motions dominate, most particularly on atoms coupled to the hydration layer. These changes are detectable in the positional disorder, e.g., in the Debye-Waller thermalB-factors. Yet, the glass transition is not detected in descriptors of backbone mean shape, e.g., the molecular size. In this work, we show that other descriptors of mean shape may be better at detecting the transition. We suggest that a property that uses the equilibrium geometryandthe backbone connectivity can exhibit larger variations with thermal fluctuations. In particular, we contrast the effects of bond length fluctuations on the mean number of overcrossings and the radius of gyration. Using the glass transition of ribonuclease-A as a test example, we show that the change in Debye-Waller factors is also reflected in the mean overcrossing numbers computed with the backbones. The approach can be used to follow other configurational transitions and to assess the effect of various external perturbations.Key words: Molecular shape fluctuations, isotropic temperature factors, anharmonic vibrations, glass phase transition, flexible molecular chains.

ISSN:0008-4042    

DOI:10.1139/v98-179

出版商:NRC Research Press    

年代:1998

数据来源: NRC