摘要:

Photodynamic therapy relies on the selective accumulation of photosensitizers within neoplastic tissue, followed by light activation to generate cytotoxic singlet oxygen. At present, PhotofrinTM, a preparation of hematoporphyrin derivatives (HPD) with the bulk of the porphyrin monomers removed, is the only clinically approved photosensitizer. Intravesical administration of Photofrin or HPD has failed to photosensitize bladder tumors. Bladder cancer is the second most common genitourinary malignancy. In 1994 there were an estimated 51 200 cases of bladder cancer with 10 600 deaths in the United States. The predominant histopathology is transitional cell carcinoma, occurring in 90–95% of these cases. Most patients (85%) have superficial disease at the time of initial diagnosis. Superficial bladder cancer is defined as disease involving the mucosa with carcinoma in situ or papillary lesions and invasion limited to submucosa. To address these limitations we have been conducting preclinical studies with perylenequinones (PQs). The majority of our effort has focused on developing and characterizing derivatives of PQs. Following site-directed modifications, we have identified certain congeners that warrant further preclinical development. These compounds are monomeric and do not effect cutaneous photosensitization beyond 24 h. With clinically relevant drug and light doses we have cured >90% of experimental subcutaneous murine tumors.Keywords: photodynamic therapy, perylenequinones, photobiology, photochemistry.

ISSN:0008-4042    

DOI:10.1139/v97-015

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

Dialkoxycarbenes with a tethered triple bond, generated from the corresponding oxadiazolines, undergo an intramolecular cyclization with the tethered alkyne moiety to give 3,3-dialkoxyvinylcarbene/1,3-dipole intermediates. The regioselectivity of the carbene cyclization is highly dependent upon the nature of the alkyne substituent. In the cases where an exocyclic vinylcarbene is generated, the vinylcarbene intermediate can undergo a synthetically useful [3 + 2] cycloaddition with either an appropriate olefin or an alkyne. This approach allows the rapid construction of some interesting heterocyclic ring systems.Keywords: carbene, dialkoxycarbene, vinylogous dialkoxycarbene, heterocycle.

ISSN:0008-4042    

DOI:10.1139/v97-016

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

The kinetics of the oxidation of 2-propanol, 1,1,1-trifluoro-2-propanol, 1,1,1,3,3,3-hexafluoro-2-propanol, 1-phenyl-2,2,2-trifluoroethanol, 1-(4-methylphenyl)-2,2,2-trifluoroethanol, 1-(3-bromophenyl)-2,2,2-trifluoroethanol, and 1-(3-nitrophenyl)-2,2,2-trifluoroethanol by potassium tetraoxoferrate(VI) have been studied under basic conditions. The products are ketones, formed in almost quantitative yields, iron(III) hydroxide, and dioxygen. The reactions are characterized by substantial enthalpies of activation (40–60 kJ/mol), very unfavorable entropies of activation, large primary deuterium isotope effects, and a positive Hammett ρ value. Both acid and base catalysis are observed. Acid catalysis is attributed to formation of a more reactive oxidant, HFeO4−, at low pH. Base catalysis is attributed partly to the conversion of the reductants to alkoxide ions at high pH, and partly to the reaction of hydroxide ion with tetraoxoferrate(VI) to give a five-coordinated species, HOFeO43−, that reacts rapidly with nucleophiles. A reaction mechanism involving formation of an intermediate ferrate ester is proposed.Keywords: oxidation, alcohols, potassium tetraoxoferrate(VI), ferrate esters, base catalysis, acid catalysis.

ISSN:0008-4042    

DOI:10.1139/v97-017

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

N,N′-[Dimethyl-(2,2′-dithiobisacetyl)]ethylenediamine (1) has been synthesized in 30% overall yield fromN,N′-dimethylethylenediamine and thioacetic acid by an improved procedure involving simultaneous deprotection and oxidative cyclization with iodine. This cyclic diamide disulfide exists in solution as a mixture of twoZ,Zand oneZ,Edisulfide, and amide ring conformers and has been characterized by nuclear Overhauser effect (NOE),1H–1H,1H–13C shift-correlated 2D-NMR and molecular modelling studies. Among theZ,Zring conformersZ,Z1andZ,Z2, the former predominates and interconverts with the latter isomer by rotation about the S—S bond with an activation energy of 14.5 ± 1.3 kcal/mol. Coalescence of N-CH3signals occurred at ca. 127 °C (500 MHz), which corresponded to an approximate barrier to amide rotation of 19.3 kcal/mol. Aromatic solvent-induced shifts in C6D6corroborated molecular mechanics and NOE predictions of amide stereochemistry. The structure of theZ,Estereoisomer of1has been determined by single-crystal X-ray diffraction at 296 K. A large geminal N-CH2inequivalence (>2 ppm in CDCl3) was observed for theZ,Zconformers. Proton chemical shifts have been calculated for the conformers of1and related molecular fragments with DFT/GIAO theory. Absolute chemical shifts are modelled within 0.2 ppm of experiment. The unusual nonequivalence of geminal N-CH2and S-CH2protons can be understood as a combination of shielding mechanisms derived from short N-methyl contacts, amide group orientation, and sulfur lone-pair disposition. An implication of these results is the possibility of using α-CH(and eventually α-CH) shifts to probe the local conformational space in cyclic peptides and other conformationally constrained rings.Keywords: amide/disulfide rotamers, conformational analysis, density functional theory, DFT/GIAO NMR shift calculations, methylene nonequivalence, molecular modelling.

ISSN:0008-4042    

DOI:10.1139/v97-018

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

The electrochemical reduction behaviour of xylenol orange, XO, in aqueous medium was studied over a pH range of 2.3–9.6 at a hanging mercury drop electrode, HMDE, on the basis of cyclic voltammetric, and double-potential step chronoamperometric and chronocoulometric data. The experimental results indicate that in acid medium (pH 2.28) the reduction of XO proceeds via an ECEC, first-order mechanism giving a single two-electron diffusion-controlled cyclic voltammetric wave. It was concluded that the rate-determining step is the protonation of the protonated anion intermediate to the final product, with rate constantk2of 0.26 s−1. At pH 7.25 the reduction follows an ECE kinetics along two cyclic voltammetric waves in which the first wave was attributed to an EC, first-order process and the second wave to an irreversible electron transfer step, E. On addition of lanthanum(III) to xylenol orange, it forms 1:1 and 1.2 La(III)–XO chelates, which are adsorbed and reduced on the HMDE at more negative potentials than the peak potential of free XO. The adsorptive cathodic stripping voltammetry, ACSV, of these chelates was studied using the square-wave, SW, method. It was found that the SW-ACSV of La(III)–XO can be applied to the determination of lanthanum at the nanomole level. Optimum conditions and the analytical method of determination were presented and discussed.Keywords: electrochemical, reduction mechanism, xylenol orange, lanthanum complex, double potential step chronoamperometry and chronocoulometry, stripping voltammetric determination.

ISSN:0008-4042    

DOI:10.1139/v97-019

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

Oligo-tridentate ligands based on alternating pyridines and pyrimidines were synthesised by Stille-type carbon–carbon bond-forming reactions. The terpyridine-like sites are designed to coalign upon metal complexation, giving rise to organized and rigidly spaced metal ions. Peripheral functionalization of the basic bis-tridentate framework was explored. The heterocycles in the ligands are in an all-transconformation about the interannular bonds as indicated by comparison of their1H NMR spectra. An X-ray crystal structure analysis of the nonchiral tris-tridentate ligand2areveals a helical structure in the solid state. The seven heterocycles form a helical structure with resulting overlap of the terminal pyridines. Their centroid-to-centroid distance is 4.523 Å with 38.8° between the planes. NMR investigations support a helical conformation in solution as well. Electrochemical and UV absorption measurements indicate that the LUMO resides on the pyrimidine moiety of the ligands.Keywords: nitrogen-containing ligands, Stille coupling, helical structure, supramolecular chemistry.

ISSN:0008-4042    

DOI:10.1139/v97-020

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

Bis(hydroxamido)hydroxooxovanadate has been found to undergo favourable condensation reactions with simple peptides such as glycylglycine, glycylglycylglycine, or glycyltyrosine to afford, in each case, three products in the approximate ratio 1:3.5:0.2. The three products had the same ligand stoichiometry and, in the case of glycylglycine, an overall formation constant of 3.3 × 103 M−1for the addition of GlyGly to bis(hydroxamido)vanadate. The51V chemical shift range of the products (close to −850 ppm) overlaps that of the starting complexes and the products may well have a coordination geometry similar to the parent complexes. The chemical shifts observed for these materials are in the range of chemical shifts observed for peroxovanadium complexes. A crystalline monomeric complex with a single glycylglycinato ligand was obtained and its crystal structure determined. The complex is zwitterionic and has a pentagonal bipyramidal coordination at vanadium with the glycine-NH2functionality coordinated in the plane of the two hydroxyalamine ligands and the amido carbonyl oxygen in the apical position. Some comparisons with peroxovanadium complexes are drawn. Crystal structure of V(O)(ONH2)2(GlyGly)•H2O: monoclinic, space groupCc;Z = 4;a = 9.1340(9) Å;b = 16.3355(15) Å;c = 7.1149(6) Å; β(°) = 103.020(7);V = 1034.31 Å3;T = 295 K;RF = 0.21 for 2513 data (I0 ≥ 2.5σ(I0)) and 197 variables.Keywords: vanadate, hydroxylamine,N-methylhydroxylamine, oxobis(hydroxamido)glycylglycinatovanadium(V), peptide complex, glycylglycine,51V NMR, crystal structure.

ISSN:0008-4042    

DOI:10.1139/v97-021

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

The concept of electron delocalization, and the possibility of aromaticity in three dimensions has been introduced, but remains relatively unexplored. This work examines the structure and energy of a series of ions generated from pentacyclo[3.3.1.13,7.01,3.05,7]decane (1). The ions considered are the dication (12+), the radical cation (1+•), the radical anion (1−•), and the dianion (12−). The dication belongs to a small group of organic compounds that shows three-dimensional electron delocalization and it has been classified as "three-dimensionally homoaromatic." The relative stability of these ions is estimated by the enthalpy change of isodesmic and disproportionation reactions using energies obtained from HF, MP2, and DFT methods. The structural changes and the reorganization of the frontier orbitals when electrons are successively added to or removed from the neutral molecule (1) are also explored. The results confirm the three-dimensional electron delocalization in12+and indicate that it is stable relative to a localized structure with similar features; however, it is highly unstable compared to the radical cation (1+•). The dianion (12−), on the other hand, did not show any evidence for electron delocalization and it is unstable relative to the radical anion (1−•).Keywords: three-dimensional aromaticity, electron derealization, resonance, radical cations, radical anions.

ISSN:0008-4042    

DOI:10.1139/v97-022

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

The hydrolysis of a number of nitroactivated esters and amides has been studied in the presence of copper-containing metallomicelles at neutral pH. The relative rates of hydrolysis in the pure metallomicelle and in co-micelles with either cetyltrimethylammonium bromide (ctab) or Triton X-100 depends on the hydrophobicity of the substrate and whether it is completely solubilized by the copper micelle. Thus it depends on the concentration of the copper micelle. At low concentrations of copper micelle (0.2 mM) where the substrate is incompletely solubilized, the reaction is faster when 2 mM ctab is added. At higher concentrations (>0.6 mM) where the substrate may be almost completely solubilized by the copper micelle, the reaction is slower when 2 mM ctab is added. For ester hydrolysis the presence of either a carboxylic acid group or a heterocyclic nitrogen atom close to the reaction centre resulted in much larger catalysis by the metallomicelle than for model compounds without these additional groups. It is postulated that these groups coordinate with the metal ion and thus present the reaction centre close to a metal-bound hydroxyl resulting in a significant increase in the rate of bond formation, which is the rate-determining step for ester hydrolysis. For amide hydrolysis the presence of a carboxyl grouporthoto the reaction centre did not lead to larger catalysis by the copper micelle than for the compound without this group. This difference is attributed to the different rate-determining steps for amide and for ester hydrolysis.Keywords: metallomicelles, ester and amide hydrolysis.

ISSN:0008-4042    

DOI:10.1139/v97-023

出版商:NRC Research Press    

年代:1997

数据来源: NRC

摘要:

Densities and vapor-liquid equilibria were determined for tetrahydrofuran with propan-1-ol and propan-2-ol systems at 298.15 K. From the experimental results, excess molar volumes and excess Gibbs free energies were calculated. Information could be obtained from the possible interaction between both chemical species in the two systems. The Prigogine–Flory–Patterson method was applied to calculate excess molar volumes. Liquid activity coefficients were calculated and correlated with different expressions existing in the literature.Keywords: excess molar volumes, vapor–liquid equilibria, activity coefficients, excess Gibbs free energies, tetrahydrofuran, propan-1-ol, propan-2-ol.

ISSN:0008-4042    

DOI:10.1139/v97-024

出版商:NRC Research Press    

年代:1997

数据来源: NRC