Esters of 1-O-Demethylthiocolchicines: Formation of Isomers in Chloroform Solution

1-O-Acetyl-1-O-demethylcolchicine, and acylated 1-O,2-O-didemethylthiocolchicines, in contrast to 2-O-acetyl-, 2-O,3-O-diacetyl- and 3-O-acetyl analogs, showed after standing in CHCl₃ solution significant changes in optical rotation, a duplication of ¹H-NMR signals, and the formation of new isomers on TLC. Solid-state X-ray diffraction of O-acetylated colchinoids and thio analogs, showed out of planar arrangements of the aromatic substituents, but the analysis could not help to explain the structures of the newly formed isomers in CHCl₃ solution.     

Mathematics,Science of Possibility ‐‐ A Critical Review

This paper supports the view that search for the applicative standpoint in mathematical education has yet to be sufficiently exploited. Mathematical propositions are considered to have both an ‘internal’ and ‘external’ role and thus a system of ‘potential models’ is evolved. Despite the stress on the applicative nature of the subject it is argued in conclusion that the position in the body of the paper is compatible with the synthetic apriority of mathematics.

     

Quasistatic Thermoviscoelastic Frictional Contact Problem with Damped Response

We analyze a problem which describes the frictional contact between a thermoviscoelastic body and a rigid foundation. The process is assumed to be quasistatic and the contact is modeled by a general normal damped response condition with friction law and heat exchange. Then we present a variational formulation of the problem, which is set in an abstract form as a system of evolution equations for the displacements and temperature. We establish the existence and uniqueness of the weak solution, using general results on evolution equations with monotone operators and fixed point arguments. Finally, we study the continuous dependence of the solution with respect to the initial data and contact conditions.     

Further observations on the anharmonic motion equation

Peters [1] discussed some theoretical aspects of the ‘ringing’ sound associated with barbershop quartet singing. These combination tones were first investigated theoretically by Helmholtz [2] who showed that the transient displacement of the ear membrane is governed by the anharmonic motion equation. Rayleigh [3] modelled the situation as an initial value problem and this is now referred to as the Rayleigh problem. Following [1] there has been a renewed interest in the problem (see [4‐8]). The intention of the present paper is to:

• illustrate the qualitative behaviour of the solutions of the Rayleigh problem by a phase plane analysis;

• describe how the method of multiple scales provides a framework within which previous analyses can be seen;

• describe an improvement to the method of multiple scales, which may also prove useful in other applications.

     

Carleman estimate for a stationary isotropic Lamé system and the applications

For the isotropic stationary Lamé system with variable coefficients equipped with the Dirichlet or surface stress boundary condition, we obtain a Carleman estimate such that (i) the right hand side is estimated in a weighted L ²-space and (ii) the estimate includes nonhomogeneous surface displacement or surface stress. Using this estimate we establish the conditional stability in Sobolev's norm of the displacement by means of measurements in an arbitrary subdomain or measurements of surface displacement and stress on an arbitrary subboundary. Finally by the Carleman estimate, we prove the uniqueness and conditional stability for an inverse problem of determining a source term by a single interior measurement.     

SPECTRAL AND PHOTOCHEMICAL PROPERTIES OF CURCUMIN

Curcumin, bis(4-hydroxy-3-methoxyphenyl)-l,6-heptadiene-3,5-dione, is a natural yellow-orange dye derived from the rhizome of Curcuma longa, an East Indian plant. In order to understand the photobiology of curcumin better we have studied the spectral and photochemical properties of both curcumin and 4-(4-hydroxy-3-methoxy-phenyl)-3-buten-2-one (hC, half curcumin) in different solvents. In toluene, the absorption spectrum of curcumin contains some structure, which disappears in more polar solvents, e.g. ethanol, acetonitrile. Curcumin fluorescence is a broad band in acetonitrile (λ_max= 524 nm), ethanol (λ_max= 549 nm) or micellar solution (λ_max= 557 nm) but has some structure in toluene (λ_max= 460, 488 nm). The fluorescence quantum yield of curcumin is low in sodium dodecyl sulfate (SDS) solution (φ= 0.011) but higher in acetonitrile (φ= 0.104). Curcumin produced singlet oxygen upon irradiation (φ > 400 nm) in toluene or acetonitrile (Φ= 0.11 for 50 μM curcumin); in acetonitrile curcumin also quenched ¹O₂ (k_q, = 7 × 10⁶ M^?1 s^?1). Singlet oxygen production was about 10 times lower in alcohols and was hardly detectable when curcumin was solubilized in a D₂O micellar solution of Triton X-100. In SDS micelles containing curcumin no singlet oxygen phosphorescence could be observed. Curcumin photogenerates superoxide in toluene and ethanol, which was detected using the electron paramagnetic resonance/spin-trapping technique with 5,5-dimethyl-pyrroline-.N-oxide as a trapping agent. Unidentified carbon-centered radicals were also detected. These findings indicate that the spectral and photochemical properties of curcumin are strongly influenced by solvent. In biological systems, singlet oxygen, superoxide and products of photodegradation may all participate in curcumin phototoxicity depending on the environment of the dye.     

PHOTOCHEMISTRY OF 2-MERCAFTOPYRIDINES. PART 2. AN EPR AND SPIN-TRAPPING INVESTIGATION USING 2-METHYL-2-NITROSOPROPANE AND aci-NITROMETHANE AS SPIN TRAPS IN AQUEOUS SOLUTIONS*

Abstract Compounds possessing a pyridine-2-thione moiety show antimicrobial, antifungal and anticancer activities. Some of them are also photochemically active and upon UV irradiation generate free radicals. In this work, employing EPR and the spin traps 2-methyl-2-nitrosopropane (MNP) and aci-nitromethane (NM), we investigated the photochemistry in aqueous solutions of N-hydroxypyridine-2-thione (used here as a sodium salt, 2-S-PyrNONa), and pyridine-2-thione (2-S-PryH), as well as photochemistry of the respective disulfides, 2,2′-dithiobis(pyridine N-oxide) [(2-S-PyrN→O)₂] and 2,2′-dithiodipyridine [(2-S-Pyr)₂]. We found that UV irradiation of 2-S-PyrNONa and of 2-S-PyrH in the presence of MNP and NM generates EPR signals of reduced spin traps in addition to signals of MNP and NM adducts with aryl-thiyl radicals, 2–.S-PyrN→O and 2–.S-Pyr. The identification of the aromatic thiyl radicals was based on comparison of EPR spectra of spin adducts generated by irradiation of 2-S-PyrNONa and 2-S-PyrH with those produced by UV photolysis of the respective disulfides (2-S-PyrN→O), and (2-S-Pyr)₂. It is concluded that pyridine-2-thione and N-hydroxypyridine-2-thione possess a photoreducing capacity and generate aromatic thiyl radicals upon UV activation. This property may be relevant to biological action of agents containing the pyridine-2-thione moiety.     

SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS—X. A SPIN-TRAPPING AND DIRECT ELECTRON SPIN RESONANCE STUDY OF THE PHOTOCHEMICAL PATHWAYS OF DAUNOMYCIN AND ADRIAMYCIN

Abstract— Irradiation of daunomycin (or adriamycin) and the spin trap 5,5-dimethyl-l-pyrroline-1-oxide (DMPO) at 490 nm in the presence or in the absence of air generated the hydroxyl radical adduct (DMPO-OH). The observed DMPO-OH signal was not affected by the addition of hydroxyl radical scavengers (ethanol, formate), suggesting that direct trapping of the hydroxyl radical was not involved. The DMPO-OH signal was insensitive to superoxide dismutase and catalase, which ruled out the possibility of superoxide or H₂O₂ involvement. These findings demonstrate that daunomycin (or adriamycin) does not generate hydroxyl radicals or superoxide radical anions when subjected to 490-nm excitation. However, when daunomycin (or adriamycin) was irradiated at 310 nm DMPO adducts derived from two carbon-centered radicals, superoxide and the hydroxyl radical were detected. The superoxide adduct of DMPO was abolished by the addition of SOD, providing unequivocal evidence for the generation of the superoxide anion radical. The daunomycin semiquinone radical, observed upon 310-nm irradiation of daunomycin in the absence of DMPO, appears to be the precursor of the superoxide radical anion. One of the carbon-centered radicals trapped by DMPO exhibited a unique set of hyperfine parameters and was identified as an acyl radical. This suggests that the known photochemical deacylation of daunomycin occurs via a homolytic cleavage mechanism. The free radicals generated photolytically from adriamycin and daunomycin may be involved in the etiology of the skin ulceration and inflammation caused by these drugs. A knowledge of the dependence of these photogenerated radicals on the wavelength of excitation may be important in the development of adriamycin and daunomycin for photodynamic therapy.     

FREE RADICAL PRODUCTION BY CHLORPROMAZINE SULFOXIDE, AN ESR SPIN-TRAPPING AND FLASH PHOTOLYSIS STUDY

Abstract— Using the spin-trapping technique we have investigated the photolysis of chlorpromazine sulfoxide and promazine sulfoxide. Photolysis of these sulfoxides in aqueous solution resulted in a species which is capable of oxidizing ascorbate, cysteine, glutathione, NADH, and azide by one electron, in addition to extracting hydrogen atoms from ethyl alcohol and dimethyl sulfoxide. These oxidations were not dependent on the presence of dissolved oxygen. The oxidizing species is proposed to be the hydroxyl free radical arising from the homolytic cleavage of the S-O bond of the sulfoxide. Flash photolysis of the chlorpromazine and promazine sulfoxides demonstrated the formation of cation radicals consistent with the loss of the hydroxyl radical from the sulfoxides. In addition we present a simple direct method for the quantitative synthesis of promazine and chlorpromazine sulfoxides from the parent promazine derivatives.