Antifungal cellulose by capsaicin grafting

Cellulose is one of the most abundant materials in nature. Besides its biological function, cellulose can be extracted from the cell wall and used in several industrial applications. Thus, it can be used in papers, pharmaceuticals, food, cosmetics and innovative materials such as nanocomposites, packaging, coatings and dispersion technology. With the aim of extending cellulose applications and producing so-called “smart” materials, new functionality can be introduced by physical or chemical modifications. Taking into account that capsaicin, the active component of chili peppers, is an excellent antifungal agent, a potential new material could be obtained by chemical reaction between this active compound and cellulose. In this work, capsaicin grafting onto cellulose using polycarboxylic acid as linking agent is proposed. The reaction occurrence was corroborated by Fourier transform infrared spectroscopy and UV–Vis spectrophotometry in reflectance mode. Modified cellulose with <2 wt% of capsaicin shows a strong change in antifungal activity with respect to the unmodified one. This activity was evaluated by the fungal growth inhibition test with two different fungi, Trametes versicolor and Gloeophyllum trabeum. Modified cellulose samples showed a high percentage of fungal growth inhibition, demonstrating the success of the cellulose modification and high antifungal power of the grafting molecule.     

DFT 1H–1H coupling constants in the conformational analysis and stereoisomeric differentiation of 6‐heptenyl‐2H‐pyran‐2‐ones: configurational reassignment of synargentolide A

Density functional theory (DFT) ¹H–¹H NMR coupling constant calculations, including solvation parameters with the polarizable continuum model B3LYP/DGDZVP basis set together with the experimental values measured by spectral simulation, were used to predict the configuration of hydroxylated 6‐heptenyl‐5,6‐dihydro‐2H‐pyran‐2‐ones 1 , 2 , 4 , and 7 , allowing epimer differentiation. Modeling of these flexible compounds requires the inclusion of solvation models that account for stabilizing interactions derived from intramolecular and intermolecular hydrogen bonds, in contrast with peracetylated derivatives ( 3 , 5 , and 6 ) in which the solvation consideration can be omitted. Using this DFT NMR integrated approach as well as spectral simulation, the configurational reassignment of synargentolide A ( 8 ) was accomplished by calculations in the gas phase among four possible diastereoisomers ( 8–11 ). Calculated ³J_H,H values established its configuration as 6R‐[4′S,5′S,6′S‐(triacetyloxy)‐2E‐heptenyl]‐5,6‐dihydro‐2H‐pyran‐2‐one ( 8 ), in contrast with the incorrect 6R,4′R,5′R,6′R‐diastereoisomer previously proposed by synthesis ( 12 ). Application of this approach increases the probability for successful enantiospecific total syntheses of flexible compounds with multiple chiral centers. Copyright © 2014 John Wiley & Sons, Ltd.     

Stereoselective Synthesis of 1,3‐Diaminotruxillic Acid Derivatives: An Advantageous Combination of CH‐ortho‐Palladation and On‐Flow [2+2]‐Photocycloaddition in Microreactors

The stereoselective synthesis of ε‐isomers of dimethyl esters of 1,3‐diaminotruxillic acid in three steps is reported. The first step is the ortho‐palladation of (Z)‐2‐aryl‐4‐aryliden‐5(4H)‐oxazolones 1 to give dinuclear complexes 2 with bridging carboxylates. The reaction occurs through regioselective activation of the ortho‐C?H bond of the 4‐arylidene ring in carboxylic acids. The second step is the [2+2]‐photocycloaddition of the C?C exocyclic bonds of the oxazolone skeleton in 2 to afford the corresponding dinuclear ortho‐palladated cyclobutanes 3 . This key step was performed very efficiently by using LED light sources with different wavelengths (465, 525 or 625 nm) in flow microreactors. The final step involved the depalladation of 3 by hydrogenation in methanol to afford the ε‐1,3‐diaminotruxillic acid derivatives as single isomers.     

Water‐Promoted Generation of a Diazairida Homobarrelene by C?C Coupling Between an Iridacyclic Alkylidene and Acetonitrile

The stable cationic iridacyclopentenylidene [Tp^Me2Ir(CHC(Me)C(Me)C H₂(NCMe)]PF₆ ( A ; Tp^Me2=hydrotris(3,5‐dimethylpyrazolyl)borate) has been obtained by α‐hydride abstraction from the iridacyclopent‐2‐ene [Tp^Me2Ir(CH₂C(Me)C(Me)C H₂)(NCMe)]. Complex A exhibits Brønsted–Lowry acidity at the Ir CH₂ and proximal (relative to Ir CH₂) methyl sites. The coordination of an extra molecule of acetonitrile to the iridium center initiates the reversible isomerization of the chelating carbon chain of A to the monodentate butadienyl ligand of complex [Tp^Me2Ir(CHC(Me)C(Me)CH₂)(NCMe)₂]PF₆, which is capable to engage in a water‐promoted C C coupling with the MeCN co‐ligands. The product is an aesthetically appealing bicyclic structure that resembles the hydrocarbon barrelene.     

Synthesis of (Carbo)nucleoside Analogues by [3+2] Annulation of Aminocyclopropanes

(Carbo)nucleoside derivatives constitute an important class of pharmaceuticals, yet there are only few convergent methods to access new analogues. Here, we report the first synthesis of thymine‐, uracil‐, and 5‐fluorouracil‐substituted diester donor–acceptor cyclopropanes and their use in the indium‐ and tin‐catalyzed [3+2] annulations with aldehydes, ketones, and enol ethers. The obtained diester products could be easily decarboxylated and reduced to the corresponding alcohols. The method gives access to a broad range of new (carbo)nucleoside analogues in only four or five steps and will be highly useful for the synthesis of libraries of bioactive compounds.     

Electrochemical Oxidation of Sulfasalazine at a Glassy Carbon Electrode

Sulfasalazine (SSZ) is a pharmaceutical compound used for the treatment of rheumatoid arthritis. The electrochemical oxidation of SSZ at a glassy carbon electrode was studied by cyclic, differential pulse and square wave voltammetry in a wide pH range. For electrolytes with pH<11.0, the oxidation is an irreversible, diffusion‐control, pH‐dependent process that involves the transfer of one electron and one proton from the hydroxyl group of the salicylic moiety. For pH>11.0 the oxidation is pH‐independent, and a pK_a≈11 was determined. The formation of a quinone‐like oxidation product that undergoes two electrons and two protons reversible redox reaction was observed. Also, UV‐vis spectra of SSZ were recorded as a function of supporting electrolytes pH. An electrochemical oxidation mechanism was proposed.     

Reactivity of Cationic Agostic and Carbene Structures Derived from Platinum(II) Metallacycles

This paper describes the formation of new platinacyclic complexes derived from the phosphine ligands PiPr₂Xyl, PMeXyl₂, and PMe₂Ar (Xyl=2,6‐Me₂C₆H₃ and Ar=2,6‐(2,6‐Me₂C₆H₃)₂‐C₆H₃) as well as reactivity studies of the trans‐[Pt(C^P)₂] bis‐metallacyclic complex 1 a derived from PiPr₂Xyl. Protonation of compound 1 a with [H(OEt₂)₂][BAr_F] (BAr_F=B[3,5‐(CF₃)₂C₆H₃]₄) forms a cationic δ‐agostic structure 4 a , whereas α‐hydride abstraction employing [Ph₃C][PF₆] produces a cationic platinum carbene trans‐[Pt{PiPr₂(2,6‐CH(Me)C₆H₃}{PiPr₂(2,6‐CH₂(Me)C₆H₃}][PF₆] ( 8 ). Compounds 4 a and 8 react with H₂ to yield the same 1:3 equilibrium mixture of 4 a and trans‐[PtH(PiPr₂Xyl)₂][BAr_F] ( 6 ), in which one of the phosphine ligands participates in a δ‐agostic interaction. DFT calculations reveal that H₂ activation by 8 occurs at the highly electrophilic alkylidene terminus with no participation of the metal. The two compounds 4 a and 8 experience C–C coupling reactions of a different nature. Thus, 4 a gives rise to complex trans‐[PtH{(E)‐1,2‐bis(2‐(PiPr₂)‐3‐MeC₆H₃)CH?CH}] ( 7 ) that contains a tridentate diphosphine–alkene ligand, through agostic C?H oxidative cleavage and C–C reductive coupling steps, whereas the C–C coupling reaction in 8 involves classical migratory insertion of its [Pt?CH] and [Pt?CH₂] bonds promoted by platinum coordination of CO or CNXyl. The mechanisms of the C?C bond‐forming reactions have also been investigated by computational methods.     

Methyl‐, Ethenyl‐, and Ethynyl‐Bridged Cationic Digold Complexes Stabilized by Coordination to a Bulky Terphenylphosphine Ligand

Reactions of the gold(I) triflimide complex [Au(NTf₂)(PMe₂Ar )] ( 1 ) with the gold(I) hydrocarbyl species [AuR(PMe₂Ar )] ( 2 a – 2 c ) enable the isolation of hydrocarbyl‐bridged cationic digold complexes with the general composition [Au₂(μ‐R)(PMe₂Ar )₂][NTf₂], where Ar =C₆H₃‐2,6‐(C₆H₃‐2,6‐iPr₂)₂ and R=Me ( 3 ), CH?CH₂ ( 4 ), or C?CH ( 5 ). Compound 3 is the first alkyl‐bridged digold complex to be reported and features a symmetric [Au(μ‐CH₃)Au]⁺ core. Complexes 4 and 5 are the first species of their kind that contain simple, unsubstituted vinyl and acetylide units, respectively. In the series of complexes 3 – 5 , the bridging carbon atom systematically changes its hybridization from sp³ to sp² and sp. Concomitant with this change, and owing to variations in the nature of the bonding within the [Au(μ‐R)Au]⁺ unit, there is a gradual decrease in aurophilicity, that is, the strength of the Au???Au bonding interaction decreases. This change is illustrated by a monotonic increase in the Au–Au distance by approximately 0.3 Å from R=CH₃ (2.71 Å) to CH?CH₂ (3.07 Å) and C?CH (3.31 Å).     

Dissociation and electrooxidation of primaquine diphosphate as an approach to the study of anti-chagas prodrugs mechanism of action

This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH-dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized. This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown. This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs.