Structure-activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues

Many analogues of the antitumor agent irofulven have been readily prepared by replacing the allylic hydroxyl with a variety of nucleophiles. Analogues of acylfulvene (the precursor to irofulven) were also prepared by Michael reaction with acrolein. The toxicity of the analogues was determined, as well as preclinical antitumor activity. Several analogues exhibited good activity in mouse xenografts. Structural requirements for activity are discussed.     

An intraindividual study of the characteristics of erythema induced by bath and oral methoxsalen photochemotherapy and narrowband ultraviolet B

We compared the characteristics of psoralen and ultraviolet A (PUVA) erythema in skin photosensitized by bath or oral methoxsalen in 20 subjects. Erythema was assessed visually and with a reflectance instrument at 24 h intervals for 7 days. In addition, narrowband ultraviolet B (TL-01 UVB) erythema was examined in 19 of these subjects at 4, 8, 12, 24, 48 and 72 h and in another nine subjects at 12, 15, 18, 21 and 24 h. Both bath and oral PUVA exhibited broad erythemal peaks beyond 72 h. For topical PUVA the lowest minimal phototoxic dose (MPD) occurred at 120 and 144 h (P = 0.01 and 0.03 compared with 72 h). Oral PUVA erythema peaked earlier at 96 h: the MPD was significantly lower at 96, 120 and 144 h compared with 72 h (P = 0.001, 0.01 and 0.02, respectively). At 120 h, bath PUVA had a significantly steeper slope compared with oral PUVA. The TL-01 UVB minimal erythema dose was significantly lower at 12 h compared with 24 h (P = 0.019). The majority of subjects were at maximal erythema at 12 h (22 of 28) and 15 h (eight of nine). Our results suggest that peak erythema for bath PUVA, oral PUVA and TL-01 UVB occurs at 120, 96 and 12-15 h, respectively.     

Synthesis and complexation of a ‘mixed’-pyridine-naphthalene homooxacalixarene

A deep-cavity ‘mixed’ octahomotetraoxacalix[2]naphthalene[2]pyridine macrocycle has been synthesised and its single-crystal X-ray structure has been determined. Molecular modeling studies suggested that this macrocycle could be an effective host for guest aromatic diol(s) similar to Wang's methylazacalixpyridines. Binding constants were determined using ¹H NMR chemical shifts changes and comparisons were made between the diols which were tested.     

Synthesis and Characterization of Liquid-Crystalline Tetraoxapentacene Derivatives Exhibiting Aggregation-Induced Emission

A series of new tetrakis(dialkoxyphenyl) dicyanotetraoxapentacene derivatives ( 1 a – c ) were prepared by reaction of the appropriate terphenyl diols with tetrafluoroterephthalonitrile in good yields. Compounds 1 b and 1 c , which bear hexyloxy and decyloxy side chains, exhibited columnar hexagonal mesophases, as shown by polarized optical microscopy, variable-temperature powder X-ray diffraction, and differential scanning calorimetry. Single-crystal X-ray diffraction of methoxy-substituted 1 a revealed that the dicyanotetraoxapentacene core is highly planar, consistent with the notion that these molecules are able to stack in columnar mesophases. A detailed photophysical characterization showed that these compounds exhibit aggregation-induced emission in solution, emission in nonpolar solvents, weak emission in polar solvents, and strong emission in the solid state both as powder and in thin films. These observations are consistent with a weakly emissive charge-transfer state in polar solvents and a more highly emissive locally excited state in nonpolar solvents.     

Synthesis and clathrates of oligomeric 2-O-naphthoide macrocycles

New macrocyclic O-naphthoides 4-6 were synthesized from dehydration reactions of 3-hydroxy- and 7-tert-butyl-3-hydroxy-2-naphthoic acids, respectively. Their X-ray structures were determined and their clathrate inclusion properties were investigated. Hexamer 6 formed an inclusion clathrate with four chloroform molecules. The trimer 5, by analogy with tri-o-thymotide, was studied for its potential optical resolution effects.     

Halide ion effect on the chloroform chemical shift in supramolecular complexation studies with tetra-n-butylammonium salts: a 1H NMR and X-ray study

A ¹H NMR spectroscopic study of tetra-n-butylammonium halides (TBAX: X = Cl^? , Br^?  or I^? ) in CDCl₃ solutions was conducted. Complexation studies of TBAX salts with different host molecules using ¹H NMR in CDCl₃ have previously revealed that the reference residual CHCl₃ proton signal had been shifted downfield. The aim of the study was to quantify the extent of these chemical shift changes with TBAX salts. Linear concentration–chemical shift relationships in each case were obtained from the resulting titration plots obtained from the addition of the TBAX salts alone to CDCl₃. Interactions in the solid state as determined by X-ray crystallography support the solution-state investigations indicating halide ion–chloroform proton interactions.     

Rayleigh-Ritz vibration analysis of Mindlin plates

The Rayleigh-Ritz method is applied to the prediction of the natural frequencies of flexural vibration of square plates having general boundary conditions. The analysis is based on the use of Mindlin plate theory so that the effects of shear deformation and rotary inertia are included. The spatial variations of the plate deflection and the two rotations over the plate middle surface are assumed to be series of products of appropriate Timoshenko beam functions. Results are presented for a number of types of plate and these demonstrate the manner of convergence of the method as the number of terms in the assumed series increases.     

Dilithium tetrabromonickelate (II) as a source of soft nucleophilic bromide : Reaction with epoxides

Dilithium tetrabromonickelate (II) in THF serves as a source of “soft” nucleophilic bromide and reacts regioselectively with epoxides to give bromohydrins in high yield.     

Fractals — An overview of potential applications to transport in porous media

We present an overview of the potential applicability of fractal concepts to various aspects of transport phenomena in heterogeneous porous media. Three examples of phenomena where a fractal approach should prove illuminating are presented. In the first example we consider pore level heterogeneities as typified by pore surface roughness. We suggest that roughness may be usefully modelled by fractal curves and surfaces and also cite experimental evidence for regarding pores as fractals. In the second example we consider a fractal network approach to modelling large-scale heterogeneities. The presence of features on all length scales in simple fractal models should capture the essential role played by the presence of heterogeneities on many scales in natural reservoirs. Studies of transport phenomena in such models may yield valuable insights into the problems of macroscopic dispersion. The final example concerns dispersion in multiphase flow. Here the fractal character is attributed to the distribution of the fluid phases rather than the porous medium itself. Again studies of transport phenomena in simple fractal models should help to clarify various problems associated with the corresponding phenomena in real reservoirs.