Substituent electrophilicities in the NMR spectra of barbituric derivatives

Comparison of the ¹H and ¹³ C NMR spectra of a series of substituted 5‐benzylidene‐N,N′‐dimethylbarbituric acids (1) revealed chemical‐shift variations of different centers that correlated with the theoretical electrophilicities or with the substituent electrophilic constant σ_ω , in an example of the usefulness of these DFT‐based indices. Copyright © 2012 John Wiley & Sons, Ltd.     

Electrospray ionization mass spectrometric fragmentation of hydroquinone derivatives

The fragmentation patterns of nine di-, tri- and tetracyclic hydroquinones with potential antitumor activity were rationalized by invoking competing mechanisms that included sterically accelerated homolytic cleavage, Meerwein-type rearrangements and dehydrations through elimination or intramolecular nucleophilic substitution.     

Change of mechanism with a change of substituents for a Zincke reaction

The reaction between N-(2,4-dinitrophenyl)-4-(4-pyridyl)pyridinium chloride and 4-aminothiophenol led to an unexpected displacement of the 2,4-dinitrophenyl group, in contrast with the normal Zincke product formed with other nucleophilic 4-substituted anilines. Evidence for a SET process was obtained from EPR spectra of the reaction mixture.     

Remote regio- and stereocontrol by the sulfinyl group: Diels–Alder reaction of sulfinyl dienols and 8,8-dimethylnaphthalene-1,4,5(8H)-trione

Diels–Alder cycloaddition of 8,8-dimethylnaphthalene-1,4,5(8H)-trione with diastereomeric hydroxysulfinyldienes proceeded with high yields and good π-facial and regioselectivities. The hydroxysulfoxide moiety controls the regio- and stereoselectivities, through hydrogen bonds in the suggested transition state.     

Theoretical insights into the regioselectivity of a Pictet‐Spengler reaction: Transition state structures leading to salsolinol and isosalsolinol

The mechanism of the cyclization step of the Pictet‐Spengler reaction between acetaldehyde and dopamine to give salsolinol and isosalsolinol was studied computationally, using density functional theory. The preferential formation in acidic media of salsolinol, the product of para‐cyclization, and the requirement of a neutral pH for the formation of the ortho‐cyclized isosalsolinol are explained in terms of 2 different mechanistic routes with an iminium ion or a phenolate‐iminium zwitterion as starting reactants.     

Factors affecting the competitive reduction of 8,8-dimethylnaphthalene-1,4,5(8H)-trione in a Diels–Alder cycloaddition with hydroxysulfinyldienes

Competing reduction and cycloaddition products were formed in the reaction of 8,8-dimethylnaphthalene-1,4,5(8H)-trione with a hydroxysulfinyldiene. The ratio of reduction to cycloaddition products depended on the stereochemistry of the diene and on the solvent employed, being higher in ethanol than in benzene. The ratio was also affected by the addition of Lewis acids, decreasing in the order BF₃ = Al₂O₃ > MgCl₂ > ZnCl₂. The results help to explain and predict the occurrence of these competing processes in Diels–Alder cycloadditions involving quinonedienophiles.     

Diketopyrrolopyrrole Derivatives as Photosensitizing Agents against Staphylococcus aureus

Diketopyrrolopyrrole (DPP) derivatives containing sulfonamide ( Sulfonamide-DPP ), pyridyl ( Dipyridyl-DPP ) and N-methylpyridyl ( MePyridyl-DPP ) substituents were assessed as antibacterial photosensitizers. Non-charged DPPs showed an intense absorption band centered at about 480 nm and green fluorescence emission (Φ_F ~ 0.7) in acetonitrile. The absorption of MePyridyl-DPP was bathochromically shifted at 510 nm, with decreased fluorescence emission. Sulfonamide-DPP and Dipyridyl-DPP photosensitized the formation of O₂(¹Δ_g) (Φ_Δ ~ 0.15–0.17), while the production induced by MePyridyl-DPP was at least 10 times lower. Furthermore, these DPPs produced a photoreduction of NBT similar to that of the control. Photodynamic inactivation induced by DPPs was first investigated at the single-bacterium level of Staphylococcus aureus attached to a surface. After 30 min irradiation, MePyridyl-DPP produced a complete eradication of the bacteria. In bacterial cell suspensions, dicationic DPP induced more than 7 log₁₀ decrease in S. aureus cell survival after 30 min irradiation. Potentiation with iodide anions allowed a complete elimination of bacteria after 15 min therapy. This compound was also effective to eliminate S. aureus cells on biofilms. The results show that MePyridyl-DPP bearing two positive groups provides an amphiphilic character to the structure that improves the interaction with the cell envelop. This effect enhances the photocytotoxic activity of MePyridyl-DPP against bacteria.     

Adsorption kinetics of deamidated antibody variants on macroporous and dextran-grafted cation exchangers. III. Microscopic studies

The kinetics of single and multicomponent adsorption of deamidated monoclonal antibody (mAb) charge variants is investigated using confocal laser scanning microscopy for two commercial cation exchangers, one with an open macroporous structure--UNOsphere S--and the other with charged dextran grafts--Capto S. Markedly different intraparticle concentration profiles are obtained, being very sharp for UNOsphere S, indicating pore diffusion control, but much more diffuse for Capto S, consistent with a solid or surface diffusion mechanism. For single-component adsorption, the mAb effective pore diffusivities for UNOsphere S are approximately D(e)=4.5×10(-8) and 8.3×10(-8) cm(2)/s at pH 5 and 7.5, respectively, while effective solid diffusivities for Capto S are D(s)=0.98×10(-9) and 5.0×10(-9) cm(2)/s at pH 5 and 7.5, respectively. Two-component adsorption at pH 7.5, where the deamidated variants are bound selectively also showed markedly different profiles for the two matrices. UNOsphere S showed distinct adsorption zones within the particles indicating that multicomponent transport occurs with continuous displacement of the more deamidated variant by the less deamidated one. Capto S, however, showed no spatial resolution of the variants within the particle during co-adsorption and very slow mass transfer during sequential adsorption suggesting that protein counter-diffusion is severely hindered in this material.