Suppression of Delayed-type Hypersensitivity and Hemolysis Induced by Previously Photooxidized Psoralen: Effect of Fluence Rate and Psoralen Concentration

Abstract— The kinetics of the formation of biologically active psoralen photooxidation (POP) products were analyzed by the biological effects produced. Effects of the UV light fluence rate and psoralen concentration during the preir-radiation were investigated to assess the yield of POP products, which were active in vivo (inducing suppression of delayed-type hypersensitivity [DTH] reaction to sheep red blood cells) and in vitro (altering the human erythrocyte membrane permeability). It was shown that the reciprocity law of the irradiation fluence rate and time was not valid in the case of POP-induced hemolysis and DTH suppression. Immunosuppressive POP products were more efficiently formed at low fluence rate (20.8 W/m²), whereas POP hemolysins were more efficiently produced at a high fluence rate (180 W/m²) of UV light. The yield of immunosuppressive POP products was enhanced in dilute psoralen solutions, while the POP hemolysins yield increased with increasing psoralen concentration. A kinetic scheme for psoralen photoproduct formation was proposed. Kinetic analysis showed that a labile intermediate was produced as the result of excitation of psoralen. This intermediate was either converted to a stable immunosuppressive POP product, or two intermediates combined to form a POP hemolysin. It is proposed that PUVA therapy conditions are more favorable for the formation of immunosuppressive rather than membrane-damaging psoralen photooxidation products.     

An Efficient Finite Element Method for Computing Spectra of Photonic and Acoustic Band-Gap Materials: I. Scalar Case

The paper describes an efficient finite element method for computing spectra of photonic and acoustic band-gap materials. In the photonic case only the scalar models are treated. The full vector model will be considered in the next publication.     

Stereochemical memory in the regioselective and diastereoselective rearrangement of tricyclo[3.3.0.0 2,4]octanes (housanes) by electron transfer (1,3-cyclopentanediyl radical cations) and acid (cyclopentyl carbenium ions) and silver-ion catalysis

The electron-transfer-catalyzed rearrangement of the housanes 5 affords regioselectively only the two cyclopentenes 6 (CH(3) migration) and 7 (R migration) by 1,2-migration of the two groups at the methano bridge to the methyl terminus. The 1,2-shift of the CH(3) group prevails, and the rearrangement ratio is essentially insensitive to the migratory aptitude of the R substituent. This stereochemical memory effect derives from the conformational impositions on the stereoelectronic requirements during the 1,2-migration in the 1,3-radical-cation intermediates. Similar regioselectivities and diastereoselectivities are observed for the TFA-catalyzed and silver(I)-ion-promoted rearrangements, whereas the rearrangement catalyzed by HClO(4) affords a complete reversal in the product selectivity and both the regioselectivity and the diastereoselectivity are much reduced. Migration to the phenyl terminus is favored to afford the 6' and 7' cyclopentenes, of which the former (CH(3) migration) dominates. For the minor regioisomer, only the cyclopentene 6 is formed by an exclusive 1,2-shift of the CH(3) group. This dichotomy in product selectivities is rationalized in terms of two distinct mechanisms for the various activation modes: a common one for the electron-transfer-induced, TFA-catalyzed, and silver(I)-ion-promoted rearrangements and a different one for HClO(4).     

Generation of 4,5-Diazacyclopentane-1,3-diyl Radical Cations by Chemical Electron Transfer (CET) Oxidation of Urazole-Bridged Bicyclic Housanes (Bicyclo[2.1.0]pentanes) and Their Chemical Transformations

4,5-Diazacyclopentane-1,3-diyl radical cations 3(*)(+)() were generated from urazole-bridged bicyclic housanes 3 through chemical oxidation by using tris(4-bromophenyl)aminium hexachloroantimonate as oxidant to afford the two olefinic products 4 and 5. Product studies establish that the bisolefins 5 are the result of double oxidation of the housanes 3, whereas the monoolefins 4 are formed by acid-catalyzed rearrangement, which can be suppressed by excess of base (2,6-di-tert-butylpyridine). In the case of dibenzyl substitution (3c), disproportionation of two monoradical species 5(H)c(*) serves as an alternative pathway to the corresponding olefins 4 and 5 because higher amounts of double oxidation product were isolated in the absence of base than expected if only a stoichiometric reaction were operating. Semiempirical MO calculations suggest that ionization takes place from one of the nitrogen lone pairs rather than from the strained central C-C bond as implied by the significantly lower (by ca. 0.5 eV) ionization potential. Furthermore, in the initially puckered radical cation, the positive charge is mainly located at the two nitrogen atoms, while after relaxation to the planar geometry, the charge shifts essentially entirely to the radical cation carbon atoms. The trapping reaction with methanol leads to the hemiaminal-type products 6 and 7, which establish the involvement of the cationic intermediates 3(H)(+)() and 5(H)(+)(). In addition, (13)C NMR spectroscopy confirmed these cationic intermediates [3(H)(+)() and 5(H)(+)()] by detection of the characteristic signals below delta 250 for carbenium ions. Unquestionably, the urazole ring significantly influences the radical cation reactivity of the housanes 3. Thus, in contrast to the corresponding homocyclic tricyclooctane derivatives, stoichiometric instead of catalytic amounts of CET oxidant are needed, the two nitrogen atoms of the hydrazino bridge stabilize the radical cation 3(*)(+)() by conjugation, and the carbonyl groups of the urazole moiety assist the deprotonation to the exocyclic double bonds to prevent 1,2 alkyl migration.     

Microanalytical Techniques Applied to Phase Identification and Measurement of Solute Redistribution at the Solid/Liquid Interface of Frozen Fe-4.3Ni Doublets

 A Fe-4.3Ni alloy has been solidified directionally by using the Bridgman system. The solidification conditions were chosen to obtain an oriented cellular structure of δ-ferrite. These are: a positive temperature gradient of about 60 K/cm and a growth rate of 6.6 μm/s. A change in these conditions can lead either to the formation of austenite or to the competitive growth of δ-ferrite/γ-austenite. The solid/liquid interface of δ-ferrite cells has been frozen and double instability has been revealed at the tip of the cells. The instability is described as the first harmonic wave of fundamental undulation, which appeared at the formerly planar solid/liquid interface. This means that a doublet structure is formed only with the imposed specific conditions of solidification. The Ni-solute redistribution after back-diffusion has been measured across the δ-ferrite doublet. Results of energy dispersive X-ray (EDX) measurements on the distribution of Ni and Fe correspond well to the theoretical prediction for redistribution developed especially for oriented structure formation (two dimensional solidification). Additionally, electron backscattered diffraction from the bulk Fe-4.3Ni alloy sample allowed us to determine the local structure, i.e. the distribution of single crystallite orientations in the microstructure. A unique correlation between fluctuations of the Ni-solute redistribution and crystalline orientations in the δ-ferrite doublets has been demonstrated. Moreover, a relationship between geometrical asymmetry of the doublets and solute redistribution has also been found.     

A density-functional study of the mechanism for the diastereoselective epoxidation of chiral allylic alcohols by the titanium peroxy complexes

The epoxidation of three stereolabeled methyl-substituted chiral allylic alcohols with (1,2)A and/or (1,3)A allylic strain, namely 3-methylbut-3-en-2-ol (1a), pent-3-en-2-ol (1b), and 3-methylpent-3-en-2-ol (1c), have been studied by the density-functional theory method, B3LYP/6-31+G(d,p). For each substrate we calculated the two prereaction complexes with Ti(OH)(4)/MeOOH (the oxidant model for Ti(O-i-Pr)(4)/t-BuOOH), their threo and erythro transition states for oxygen transfer, and the corresponding product complexes. For substrate 1a, the erythro transition state is 0.91 kcal/mol of lower energy than the threo one; for substrates 1b and 1c, the threo compared to the erythro transition states are by 1.05 and 0.21 kcal/mol more favorable, respectively. The threo/erythro product ratios have been estimated from the computed free energies for the competing threo and erythro transition states 3a-c in CH(2)Cl(2) solution to be 12:88 (1a), 92:8 (1b), and 77:23 (1c), which are in good accordance with the experimental values 22:78 (1a), 91:9 (1b), and 83:17 (1c). The diastereoselectivity of this diastereoselective oxyfunctionalization is rationalized in terms of the competition between (1,3)A and (1,2)A strain and the electronic advantage for the spiro transition state. In addition, solvent effects are also play a role for the diastereoselectivity at the same time.     

Synthesis and reactions of the cyclic silyl peroxide 1,1,4,4-tetramethyl-2,3-dioxa-1,4-disilacyclohexane

The first simple cyclic silyl peroxide, namely 1,1,4,4,-tetramethyl-1,4-disila-2,3-dioxane (1), was prepared by classical synthetic methodology from its corresponding cyclic disilazane and the urea complex of hydrogen peroxide.     

The 185-nm photochemistry of 2,3-diazabicyclo[2.2.1]heptene and of its denitrogenation products bicyclo[2.1.0]pentane and cyclopentene

The 185-nm denitrogenation of 2,3-diazabicyclo[2.2.1]heptene ($\text{1}$) afforded bicyclo[2.1.0]-pentane ($\text{2}$) and cyclopentene ($\text{3}$) presumably via a “hot” cyclopentane-1,3-diyl diradical ($\text{8}$); 1,4-pentadiene ($\text{4}$) and methylenecyclobutane ($\text{5}$) were secondary products of the 185-nm photolysis of ($\text{2}$) and ($\text{3}$).     

cis-Stilbene and (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)benzene as mechanistic probes in the Mn(III)(salen)-catalyzed epoxidation: influence of the oxygen source and the counterion on the diastereoselectivity of the competitive concerted and radical-type oxygen transfer

cis-Stilbene (1) has been epoxidized by a set of diverse oxygen donors [OxD], catalyzed by the Mn(III)(salen)X complexes 3 (X = Cl, PF(6)), to afford a mixture of cis- and trans-epoxides 2. The cis/trans ratios range from 29:71 (extensive isomerization) to 92:8, which depends both on the oxygen source [OxD] and on the counterion X of the catalyst. When (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)-benzene (4) is used as substrate, a mechanistic probe which differentiates between radical and cationic intermediates, no cationic ring-opening products are found in this epoxidation reaction; thus, isomerized epoxide product arises from intermediary radicals. The dependence of the diastereoselectivity on the oxygen source is rationalized in terms of a bifurcation step in the catalytic cycle, in which concerted Lewis-acid-activated oxygen transfer competes with stepwise epoxidation by the established Mn(V)(oxo) species. The experimental counterion effect is attributed to the computationally assessed ligand-dependent reaction profiles and stereoselectivities of the singlet, triplet, and quintet spin states available to the manganese species.     

Calculation for an Oriented Eutectic Interface of Constant Curvature

Calculation of interface shape for oriented eutectic growth has been proposed for regular structure formation. The constant interface curvature has been applied in the analysis. The obtained function contains some physical factors which affects the formation of concave-convex interface. The proposed approach has been related to the theory of completely coupled growth.