Shape recognition of alkylammonium ions by 1,3-bridged calix[5]arene crown-6 ethers: endo- vs exo-cavity complexation

A series of tri-O-substituted 1,3-bridged calix[5]arene crown-6 ethers bearing alkyl, arylalkyl, alkoxyalkyl, and alkoxycarbonylmethyl residues at the lower rim and either (t)()Bu or H substituents at the upper rim have been synthesized. (1)H NMR studies have shown that p-tert-butylcalix[5]crowns, irrespective of the size and nature of their lower rim pendant groups, adopt preorganized conelike conformations, whereas p-H-calix[5]crowns with bulky substituents preferentially exist in solution as partial cone conformers (C(1) symmetry). Calix[5]crown derivatives behave as mono- or ditopic receptors for isomeric butylammonium ions, forming endo-cavity (inside the calixarene cup) and/or exo-cavity (at the crown ether moiety) 1:1 complexes according to the shape of the guest. These two binding modes can be clearly distinguished and monitored by (1)H NMR titration experiments.     

New Cyclophanes as Initiator Cores for the Construction of Dendritic Receptors: Host-guest complexation in aqueous solutions and structures of solid-state inclusion compounds

Cyclophanes 3 and 4 were prepared as initiator cores for the construction of dendrophanes (dendritic cydophanes) 1 and 2 , respectively, which mimic recognition sites buried in globular proteins. The tetra-oxy[6.1.6.1]paracyclophane 3 was prepared by a short three-step route (Scheme 1) and possesses a cavity binding site shaped by two diphenylmethane units suitable for the inclusion of flat aromatic substrates such as benzene and naphthalene derivatives as was shown by ¹H-NMR binding titrations in basic D₂O phosphate buffer (Table 1). The larger cyclophane 4 , shaped by two wider naphthyl(phenyl)methane spacers, was prepared in a longer, ten-step synthesis (Scheme 2) which included as a key intermediate the tetrabromocyclophane 5 . ¹H-NMR Binding studies in basic borate buffer in D₂O/CD₃OD demonstrated that 4 is an efficient steroid receptor. In a series of steroids (Table 1), complexation strength decreased with increasing substrate polarity and increasing number of polar substituents; in addition, electrostatic repulsion between carboxylate residues of host and guest also affected the binding affinity strongly. The conformationally flexible tetrabromocyclophane 5 displayed a pronounced tendency to form solid-state inclusion compounds of defined stoichiometry, which were analyzed by X-ray crystallography (Fig. 2). 1,2-Dichloroethane formed a cavity inclusion complex 5a with 1:1 stoichiometry, while in the 1:3 inclusion compound 5b with benzene, one guest is fully buried in the macrocyclic cavity and two others are positioned in channels between the Cyclophanes in the crystal lattice. In the 1:2 inclusion compound 5c , two toluene molecules penetrate with their aromatic rings the macrocyclic cavity from opposite sides in an antiparallel fashion. On the other hand, p-xylene (= 1,4-dimethylbenzene) in the 1:1 compound 5d is sandwiched between the cyclophane molecules with its two Me groups penetrating the cavities of the two macrocycles. In the 1:2 inclusion compound 5e with tetralin (= 1,2,3,4-tetrahydronaphthalene), both host and guest are statically disordered. The shape of the macrocycle in 5a – e depends strongly on the nature of the guest (Fig. 4). Characteristic for these compounds is the pronounced tendency of 5 to undergo regular stacking and to form channels for guest inclusion; these channels can infinitely extend across the macrocyclic cavities (Fig. 6) or in the crystal lattice between neighboring cyclophane stacks (Fig. 5). Also, the crystal lattice of 5c displays a remarkable zig-zag pattern of short Br…?O contacts between neighboring macrocycles (Fig. 7).     

Proton controlled intramolecular communication in dinuclear ruthenium(II) polypyridine complexes

The synthesis and characterization of two dinuclear ruthenium polypyridyl complexes based on the bridging ligands 5,5'-bis(pyridin-2' '-yl)-3,3'-bis(1H-1,2,4-triazole) and 5,5'-bis(pyrazin-2' '-yl)-3,3'-bis(1H-1,2,4-triazole) and of their mononuclear precursors are reported. The dinuclear compounds have been prepared by a Ni(0) catalyzed coupling of a mononuclear ruthenium(II) polypyridyl complex containing a brominated triazole moiety. Electrochemical and photophysical studies indicate that, in these dinuclear complexes, the protonation state of the bridge may be used to tune the intercomponent interaction between the two metal centers and that these species act as proton driven three-way molecular switches that can be read by electrochemical or luminescence techniques.     

A study of the reaction kinetics of electrogenerated superoxide ion with benzylbromide

The reaction kinetics between O₂^? and C₆H₅CH₂Br has been investigated in N,N′-dimethylformamide by electroanalytical techniques. A mechanism is proposed in which two molecules of the primary electrode product regenerate, via a following chemical reaction, one molecule of the original electroactive species. Furthermore, evidence for a S_N2 reaction mechanism between O₂^? and C₆H₅CH₂Br has been obtained. Second order rate constants resulted to be 11000 M^?1s^?1 and 3000 M^?1s^?1at room temperature and 0°C, respectively. The main products of the reaction were found to be benzylalcohol, benzaldehyde, benzene and biphenyl.     

New sesquiterpenoids from the sponge axinella cannabina

The structures of three sesquiterpenoids, axisothiocyanate-2(4), axamide-1(5) and axamide-2(6), present in the marine sponge Axinella cannabina, have been determined on the basis of chemical and spectral evidences.     

Dendrophanes: Water-soluble dendritic receptors as models for buried recognition sites in globular proteins

Water-soluble dendritic cyclophanes (dendrophanes) of first ( 1 , 4 ), second ( 2 5 ), and third generation ( 3 6 ) with poly(ether amide) branching and 12, 36, and 108 terminal carboxylate groups, respectively, were prepared by divergent synthesis, and their molecular recognition properties in aqueous solutions were investigated. Dendrophanes 1 – 3 incorporate as the initiator core a tetraoxa[6.1.6.1]paracyclophane 7 with a suitably sized cavity for inclusion complexation of benzene or naphthalene derivatives. The initiator core in 4 – 6 is the [6.1.6.1]cyclo-phane 8 shaped by two naphthyl(phenyl) methane units with a cavity suitable for steroid incorporation. The syntheses of 1 – 6 involved sequential peptide coupling to monomer 9 , followed by ester hydrolysis (Schemes 1 and 4), Purification by gel-permeation chromatography (GPC; Fig. 3) and full spectral characterization were accomplished at the stage of the intermediate poly(methyl carboxylates) 10 – 12 and 23 – 25 , respectively. The third-generation 108-ester 25 was also independently prepared by a semi-convergent synthetic strategy, starting from 4 (Scheme 5). All dendrophanes with terminal ester groups were obtained in pure form according to the ¹³C-NMR spectral criterion (Figs, 1 and 5). The MALDI-TOF mass spectra of the third-generation derivative 25 (mol. wt. 19328 D) displayed the molecular ion as base peak, accompanied by a series of ions [M – n(1041 ± 7)]⁺, tentatively assigned as characteristic fragment ions of the poly(ether amide) cascade. A similar fragmentation pattern was also observed in the spectra of other higher-generation poly(ether amide) dendrimers. Attempts to prepare monodisperse fourth-generation dendrophanes by divergent synthesis failed. ¹H-NMR and fluorescence binding titrations in basic aqueous buffer solutions showed that dendrophanes 1 – 3 complexed benzene and naphthalene derivatives, whereas 4 – 6 bound the steroid testosterone. Complexation occurred exclusively at the cavity-binding site of the central cyclophane core rather than in fluctuating voids in the dendritic branches, and the association strength was similar to that of the complexes formed by the initiator cores 7 and 8 , respectively (Tables 1 and 3). Fluorescence titrations with 6-(p-toluidino)naphthalene-2-sulfonate as fluorescent probe in aqueous buffer showed that the micropolarity at the cyclophane core in dendrophanes 1 - 3 becomes increasingly reduced with increasing size and density of the dendritic superstructure; the polarity at the core of the third-generation compound 3 is similar to that of EtOH (Table 2). Host-guest exchange kinetics were remarkably fast and, except for receptor 3 , the stabilities of all dendrophane complexes could be evaluated by ¹H-NMR titrations. The rapid complexation-decomplexation kinetics are explained by the specific attachment of the dendritic wedges to large, nanometer-sized cyclophane initiator cores, which generates apertures in the surrounding dendritic superstructure.     

Digital simulation of cyclic voltammetric experiments for non-first-order electrode reactions

Application of the explicit finite-difference simulation method to linear-sweep cyclic voltammetry in the case of non-first-order electrode reactions is described. Reversible, quasi-reversible and totally irreversible electrode reactions with reaction orders > 1 or < 1 are discussed. Simple criteria for evaluating the kinetic parameters are proposed. The accuracy of the proposed method is checked by comparing the results obtained with literature data.     

Simplex optimization procedure for evaluating equivalence points in sigmoidal and segmented titration curves

The use of the simplex procedure as a non-linear least-squares curve-fitting method is proposed for evaluation of equivalence points in sigmoidal and segmented titration curves. The application of this procedure to theoretical curves affected by different amounts of random noise indicates its effectiveness and accuracy for locating the correct end-point in titrations characterized by very low reaction constants. The relevant results are compared with those obtained by other regression methods as well as by the first-derivative and Gran approaches.     

Interrelations between the parasitophorous vacuole of Toxoplasma gondii and host cell organelles.

Toxoplasma gondii, the causative agent of toxoplasmosis, is capable of actively penetrating and multiplying in any nucleated cell of warm-blooded animals. Its survival strategies include escape from fusion of the parasitophorous vacuole with host cell lysosomes and rearrangement of host cell organelles in relation to the parasitophorous vacuole. In this article we report the rearrangement of host cell organelles and elements of the cytoskeleton of LLCMK2 cells, a lineage derived from green monkey kidney epithelial cells, in response to infection by T. gondii tachyzoites. Transmission electron microscopy made on flat embedded monolayers cut horizontally to the apical side of the cells or field emission scanning electron microscopy of monolayers scraped with scotch tape before sputtering showed that association of mitochondria to the vacuole is much less frequent than previously described. On the other hand, all parasitophorous vacuoles were surrounded by elements of the endoplasmic reticulum. These data were complemented by observations by laser scanning microscopy using fluorescent probes from mitochondria and endoplasmic reticulum and reinforced by three-dimensional reconstruction from serial sections observed by transmission electron microscopy and labeling of mitochondria and endoplasmic reticulum by fluorescent probes.     

Determination of moxifloxacin in tablets and human urine by square-wave adsorptive voltammetry

This work presents an electroanalytical methodology developed for square-wave voltammetry based in the electrochemical reduction in hanging mercury drop electrode (HMDE), which is simple, fast, reliable and sensitive for determination of moxifloxacin (MOXI) in tablets and spiked urine human samples. The support electrolyte that provided a more defined and intense peak current for MOXI determination was the phosphate buffer 0.04 mol l^{− 1} pH 8.0. In the best-optimized conditions the drug presented an only peak of reduction at − 1.38 V vs. Ag/AgCl, using an E_acc. of − 0.30 V. An LOD of 0.44 and 3.20 ng ml^{− 1} and an LOQ of 1.46 and 10.60 ng ml^{− 1} were found for the pure standard of moxifloxacin and in the presence of matrix, respectively. A good recovery was obtained for assay spiked urine samples and a good quantification of MOXI was achieved in a commercial formulation. The methodology proposed was more sensitive than the spectrofluorimetric and spectrophotometric method with precision and accuracy equivalent.