Equilibrium and NMR relaxometric studies on the s-triazine-based heptadentate ligand PTDITA showing high selectivity for Gd3+ ions

A complete potentiometric and NMR relaxometric solution study on the heptadentate 2,2',2″,2'″-[(6-piperidinyl-1,3,5-triazine-2,4-diyl)dihydrazin-2-yl-1-ylidene]tetraacetic acid (PTDITA) ligand has been carried out. This ligand is based on the 1,3,5-triazine ring with two hydrazine-N,N-diacetate groups in positions 2 and 4 and a piperidine moiety in position 6. The introduction of the triazine ring into the ligand backbone is expected to modify its flexibility and then to affect the stability of the corresponding complexes with transition-metal and lanthanide ions. Thermodynamic stabilities have been determined by pH potentiometry, UV spectrophotometry, and (1)H NMR spectroscopy for formation of the complexes with Mg(2+), Ca(2+), Cu(2+), Zn(2+), La(3+), Gd(3+), and Lu(3+) ions. PTDITA shows a good binding affinity for Gd(3+) (logK = 18.49, pGd = 18.6) and an optimal selectivity for Gd(3+) over the endogenous Ca(2+), Zn(2+), and Cu(2+) (K(sel) = 6.78 × 10(7)), which is 3 orders of magnitude higher that that reported for Gd(DTPA) (K(sel) = 2.85 × 10(4)). This is mainly due to the lower stability of the Cu(II)- and Zn(II)(PTDITA) complexes compared to the corresponding DTPA complexes, which suggests an important role of the triazine ring on the selectivity for the Gd(3+) ion. The relaxometric properties of Gd(PTDITA) have been investigated in aqueous solution by measuring the (1)H relaxivity as a function of the pH, temperature, and magnetic field strength (nuclear magnetic relaxation dispersion profile). Variable-temperature (17)O NMR data have provided direct information on the kinetic parameters for exchange of the coordinated water molecules. A simultaneous fit of the data suggests that the high relaxivity value (r(1) = 10.2 mM(-1) s(-1)) is a result of the presence of two inner-sphere water molecules along with the occurrence of relatively slow rotation and electronic relaxation. The water residence lifetime, (298)τ(M) = 299 ns, is quite comparable to that of clinically approved magnetic resonance imaging contrast agents. The displacement of the inner-sphere water molecules by bidentate endogeneous anions (citrate, phosphate, and carbonate) has also been evaluated by (1)H relaxometry. In general, the binding interaction is markedly weak, and only in the case of citrate, a ca. 35% decrease in relaxivity was observed in the presence of 60 equiv of the anion. Phosphate and carbonate also interact with the paramagnetic ion, likely as monodentate ligands, but formation of the ternary complex is accompanied by a modest increase of r(1) due to the contribution of second-sphere water molecules.     

Self‐Assembled PAA‐Based Nanoparticles as Potential Gene and Protein Delivery Systems

A series of nanoparticles is prepared via layer‐by‐layer assembly of oppositely charged, synthetic biocompatible polyamidoamine polymers as potential carriers. Particle size, surface charge and internal chain mobility are quantified as a function of the polymer type and number of layers. The effect of addition of surfactant is examined to simulate the effects of nanoparticle dissolution. The cyctotoxicity of these particles (in epithelia and murine cell lines) are orders of magnitude lower than polyethyleneimine controls. Stable nanoparticles may be prepared from mixtures of strongly, oppositely charged polymers, but less successfully from weakly charged polymers, and, given their acceptable toxicity characteristics, such modularly designed constructs show promise for drug and gene delivery.

     

Solvent-Free Microwave-Assisted Organic Reactions Preparation of β-Keto Esters

Microwave technique has been utilised in the preparation of β-keto esters. Two different procedures are described: transesterification of β-keto esters and ring opening of 2,2,6-trimethyl-1,3-dioxin-4-one.     

Studies related to cephalosporins. Part 2 . Displacement reactions on 3-bromomethylcephems with salts of carboxylic acids

The reactivity of Δ³- and Δ²-3-bromomethylcephems toward carboxylate nucleophiles has been studied. The Δ³-bromomethylcephem 1 , less reactive than the Δ²-analogue 4 , is converted in high yields into 3-acyl-oxymethyl-3-cephems 2a-d , generally with no isomerization of the double bond, only within a narrow range of conditions. In particular, the Δ³-7-aminocephalosporanic acid (7-ACA) derivative 2a has been obtained as the only product in 91% yield by treatment of 1 with triethylammonium acetate in acetic acid. The Δ²-bromomethyl-cephem 4 is easily converted into the Δ²-acyloxymethyl-cepheras 5a-d without double bond isomerization, in very high yields.     

Surfactant Hydrogels for the Dispersion of Carbon‐Nanotube‐Based Catalysts

Novel hydrogel phases based on positively charged and zwitterionic surfactants, namely, N‐[p‐(n‐dodecyloxybenzyl)]‐N,N,N‐trimethylammonium bromide (pDOTABr) and p‐dodecyloxybenzyldimethylamine oxide (pDOAO), which combine pristine carbon nanotubes (CNTs), were obtained, thus leading to stable dispersions and enhanced cross‐linked networks. The composite hydrogel featuring a well‐defined nanostructured morphology and an overall positively charged surface was shown to efficiently immobilise a polyanionic and redox‐active tetraruthenium‐substituted polyoxometalate (Ru₄POM) by complementary charge interactions. The resulting hybrid gel has been characterised by electron microscopy techniques, whereas the electrostatic‐directed assembly has been monitored by means of fluorescence spectroscopy and ζ‐potential tests. This protocol offers a straightforward supramolecular strategy for the design of novel aqueous‐based electrocatalytic soft materials, thereby improving the processability of CNTs while tuning their interfacial decoration with multiple catalytic domains. Electrochemical evidence confirms that the activity of the catalyst is preserved within the gel media.     

New Chemistry of α-Silyl Vinylsulfides

α-Silyl Vinylsulfides, obtained in a stereoselective manner through enethiolizable silyl thioketones, can be used for the synthesis of vinylsulfides and vinylsilane with a specific geometry, and for the preraration of bicyclic and open chain thiofunzionalized enones.     

Molecular volume calculation using AM1 semi-empirical method toward diffusion coefficients and electrophoretic mobility estimates in aqueous solution

Diffusion coefficients and electrophoretic mobility are two important physicochemical parameters used in mass transport phenomenon studies. The volume of the solute is required to determine or estimate these parameters. Classical methods, such as the LeBas method are commonly used. However, although valid, this method may represent a boring and time-consuming task, depending on the nature and number of compounds to be calculated. In this study, the volumes of a series of neutral and charged substances of the main functional groups present in organic molecules, amino acids, drugs and diverse compounds, such as cytosine and glucose, were calculated according to the LeBas method (V_M) and the AM1 semi-empirical method, V_W(AM1). The latter showed to be statistically coincident with the former. Employed as a pure value or corrected by the LeBas molar volume, the AM1 molecular volume was also demonstrated to estimate the diffusion coefficients in infinite aqueous dilution within an acceptable average error, according to the Othmer–Thakar, Wilke–Chang and Hayduk–Laudie methods, as well as the electrophoretic mobility of charged substances, such as carboxylates and protonated amines. According to these results, the AM1 method was seen to be statistically valid to calculate molecular volume. Many advantages in the construction of most diverse structures were noted, as well as a reduction in time and an increase in the quality of the information, when run on molecular modeling software.     

Mechanistic investigation of the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes

The mechanism for the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes with electrophilic halogenation reagents has been investigated by using experimental and computational methods. These studies have led us to propose a mechanism for the reaction that proceeds through an initial N-chlorination of the chiral catalyst-substrate complex, followed by a 1,3-sigmatropic shift of the chlorine atom to the enamine carbon atom. The suggested reaction course is different from previously proposed mechanisms for organocatalytic enamine reactions, in which the carbon-electrophile bond is formed directly. Furthermore, the rate-determining step in the overall reaction was determined and the presence of nonlinear effects was probed.