Calix[6]arene-based cuprous "funnel complexes": a mimic for the substrate access channel to metalloenzyme active sites

Two calixarene-based model systems (a and b) for monocopper enzymes are compared. Both present a tris(pyridine) coordination site for Cu that mimics the imidazole-rich neutral binding site in enzymes. Upon reaction with 1 equiv of copper(I), the tridentate ligands gave rise to ill-defined unsymmetrical complexes. However, in the presence of an organonitrile RCN (R = Me, Et, Ph), tetrahedral species were obtained, with the nitrilo ligand included in the calixarene hydrophobic cone. System b presents a larger cavity than system a, with a wider opening thanks to the removal of three tBu groups from the calixarene structure. As a result, the recognition pattern for MeCN vs PhCN is inverted, and the relative affinity constants differ by 3 orders of magnitude. The mechanism of the acetonitrile exchange at the cuprous centers was studied by (1)H NMR spectroscopy. Thermodynamic and kinetic data show that it follows a dissociative pathway in both cases. The main differences between systems a and b stem from the presence of a door that entraps the guest in case a. In system b indeed, the removal of three calixarene tBu groups led to a 100-fold acceleration of the MeCN exchange rate. Hence, these supramolecular systems provide a rare and interesting model for the hydrophobic substrate channel giving access to a metalloenzyme active site.     

Synthesis of branched oxime-linked peptide mimetics of the MUC1 containing a universal T-helper epitope

Our goal was to develop mimics of MUC1, highly immunogenic to induce an efficient immune response against the tumor-associated form of MUC1, and sufficiently different from the natural antigen to bypass the tolerance barrier in humans. With the aim of obtaining a well-defined peptide construct as a means of evoking the precise immune responses required in immunotherapy, we synthesized artificial mimics of the MUC1 protein composed of two MUC1 repeat units of inverse orientation and a universal T-helper epitope. To synthesize these heteromeric peptide constructs, we followed a convergent approach using chemoselective ligation based on oxime chemistry. A stem peptide was first synthesized bearing two orthogonally masked aldehydes. After successive deprotection, two oxime bonds can be specifically generated. The proposed strategy proved to be concise and robust, and allowed the synthesis of the tri-branched protein in a very satisfactory yield. The different constructs were tested for their ability to generate antibodies able to recognize the MUC1 protein.     

Syntheses and structures of structurally diverse potassium beta-diketiminates derived from the ligand [(N(SiMe3)C(Ph))2CH

The compounds [K((mu-N(SiMe3)C(Ph))2CH)(thf)2]infinity 1, [K(mu-N(SiMe3)C(Ph)C(H)C(Ph)NH)L]2 [L = (thf)2 2, tmen 3], [K(mu-NSi(Me)2C(Ph)C(H)C(Ph)N)(thf)3]2 4 and [K(N(H)C(Ph))2CH](thf)0.5 5 have been prepared from K[(N(SiMe3)C(Ph))2CH] and the X-ray structures of 1-4 are reported.     

Second-order Green's function calculations of the ionization potential of a (H2)7 chain embedded in a homogeneous electric field

Summary The vertical ionization potential and the related pole strength of a model alternant chain of 14 hydrogen atoms subject to a homogeneous electric field, parallel to the chain and of increasing intensity are calculated, in the framework of a 6–31G** basis set, at the second-order level of the many-body Green's function theory. Trends observed with orbital relaxation, pair removal and pair relaxation effects are interpreted in terms of deformations of the electron density.     

Co-eluent effect in partition chromatography. Rhamnose-xylose separation with strong and weak cation-exchangers in aqueous ethanol

The effect of ethanol in aqueous eluent on the chromatographic separation was studied at 298 K. Two sugars, L-rhamnose and D-xylose, were separated by using strong and weak cation-exchangers as a stationary phase. The ionic form of the resins was Na+ or Ca2+. The separations were carried out with sugar feed concentrations up to 35 wt% and with both low (about 1%) and high (about 10%) feed volume to bed volume ratios. The separation of the sugars was improved by adding ethanol into the eluent. The separation was also significantly enhanced when the weak cation-exchangers with the greatest affinity for water were used instead of strong cation-exchangers as a separation medium for the sugars having different hydrophilicities. The experimental data were successfully explained with a rate-based column model, which accounted for the volume changes of the stationary phase. A thermodynamic sorption model was utilized in column calculations.     

Dinitrogen reduction by TmII,DyII, and NdII with simple amide and aryloxide ligands

Dinitrogen can be reduced to the planar M2(mu-eta2:eta2-N2) structure without employing cyclopentadienyl or complicated polydentate ligands using the recently discovered divalent oxidation states of Tm(II), Dy(II), and Nd(II). Complexes of these ions with common monodentate amide and aryloxide ligands can effect N2 reduction. THF solutions of LnI2 (Ln = Tm, Dy) in the presence of 2 equiv of NaN(SiMe3)2 reduce dinitrogen to form {[(Me3Si)2N]2(THF)Ln}2(mu-eta2:eta2-N2) complexes that have planar Ln2N2 units and 1.264(7) and 1.305(6) A NN bonds consistent with (N2)2- moieties. With the stronger reductant Nd(II), aryloxides are sufficient ancillary ligands: the NdI2/2KOC6H3tBu2-2,6 (KOAr) system forms [(ArO)2(THF)2Nd]2(mu-eta2:eta2-N2), which has a 1.242(7) A NN bond.     

Kinetics of formation and dissociation of lanthanide(III) complexes with the 13-membered macrocyclic ligand TRITA4-

The tetraazamacrocyclic ligand TRITA(4-) is intermediate in size between the widely studied and medically used 12-membered DOTA(4-) and the 14-membered TETA(4-). The kinetic inertness of GdTRITA(-) was characterized by the rates of exchange reactions with Zn(2+) and Eu(3+). In the Zn(2+) exchange, a second order [H(+)] dependence was found for the pseudo-first-order rate constant (k(0)=(4.2 +/- 0.5) x 10(-7) s(-1); k'=(3.5 +/- 0.3) x 10(-1) M(-1)s(-1), k" =(1.4 +/- 0.4) x 10(3) M(-2)s(-1)). In the Eu(3+) exchange, at pH <5 the rate decreases with increasing concentration of the exchanging ion, which can be accounted for by the transitional formation of dinuclear GdTRITAEu(2+) species. At physiological pH, the kinetic inertness of GdTRITA(-) is considerably lower than that of GdDOTA(-)(t(1/2)= 444 h (25 degrees C) vs. 3.8 x 10(5) h (37 degrees C), respectively). However, GdTRITA(-) is still kinetically more inert than GdDTPA(2-), the most commonly used MRI contrast agent (t(1/2)= 127 h). The formation reactions of LnTRITA(-) complexes (Ln = Ce, Gd and Yb) proceed via the rapid formation of a diprotonated intermediate and its subsequent deprotonation and rearrangement in a slow, OH(-) catalyzed process. The stability of the LnH(2)TRITA* intermediates (log K(LnH2L*)= 3.1-3.9) is lower than that of the DOTA-analogues. The rate constants of the OH(-) catalyzed step increase with decreasing lanthanide ion size, and are about twice as high as for DOTA-complexes.     

Simultaneous determination of chromium(III) and chromium(VI) in aqueous solutions by ion chromatography and chemiluminescence detection.

A method for the simultaneous determination of chromium(iii) and chromium(vi) in a flow system based on chemiluminescence was developed. A Dionex cation-exchange guard column was used to separate chromium(iii) from chromium(vi), and chromium(vi) was reduced by potassium sulfite, whereupon both species were detected by use of the luminol-hydrogen peroxide chemiluminescence system. Linear calibration for both species was established over the concentration range 1-1000 micrograms l-1. The precision at the 20 micrograms l-1 level was 3.5% for chromium(iii) and 3.3% for chromium(vi), respectively. The detection limit was 0.5 micrograms l-1 for both species. Data were in agreement with Zeeman-effect background corrected atomic absorption spectrometry measurements.