Structural role of counterions adsorbed on self-assembled peptide nanotubes

Among noncovalent forces, electrostatic ones are the strongest and possess a rather long-range action. For these reasons, charges and counterions play a prominent role in self-assembly processes in water and therefore in many biological systems. However, the complexity of the biological media often hinders a detailed understanding of all the electrostatic-related events. In this context, we have studied the role of charges and counterions in the self-assembly of lanreotide, a cationic octapeptide. This peptide spontaneously forms monodisperse nanotubes (NTs) above a critical concentration when solubilized in pure water. Free from any screening buffer, we assessed the interactions between the different peptide oligomers and counterions in solutions, above and below the critical assembly concentration. Our results provide explanations for the selection of a dimeric building block instead of a monomeric one. Indeed, the apparent charge of the dimers is lower than that of the monomers because of strong chemisorption. This phenomenon has two consequences: (i) the dimer-dimer interaction is less repulsive than the monomer-monomer one and (ii) the lowered charge of the dimeric building block weakens the electrostatic repulsion from the positively charged NT walls. Moreover, additional counterion condensation (physisorption) occurs on the NT wall. We furthermore show that the counterions interacting with the NTs play a structural role as they tune the NTs diameter. We demonstrate by a simple model that counterions adsorption sites located on the inner face of the NT walls are responsible for this size control.     

Thermodynamics of translesion synthesis across a major DNA adduct of antitumor oxaliplatin: differential scanning calorimetric study

Differential scanning calorimetry (DSC) was used to measure the thermodynamic changes associated with translesion synthesis across major lesion induced in DNA by antitumor oxaliplatin [1,2-d(GG) intrastrand cross-link]. Insertion of matched nucleotides dC at the primer terminus (across unique 3'- or 5'-dG in the unplatinated template) and subsequent extensions resulted in an incremental increase in thermodynamic parameters. In contrast, incorporation of dC opposite either platinated dG in the intrastrand cross-link formed in the template strand and subsequent extensions by one nucleotide resulted only in little changes in thermodynamics. A similar thermodynamic delay was observed for a control template primer containing a dG:dT mismatch across 3'- or 5'-dG in the template and subsequent Watson-Crick primer extensions. The thermodynamic scarcity generated by either the lesion or mismatches was not localized but extended to the 5'-downstream sites, which may be connected with the phenomenon termed "short-term memory" of replication errors retained by some DNA polymerases responding to DNA damages or mismatches. Interestingly, formation of the 1,2-d(GG) intrastrand cross-link of oxaliplatin altered the overall DSC profiles of the dG:dT mismatch template/primers only in a very small extent. While addition of matched nucleotide dC across either dG in the template strand was thermodynamically favored over the presence of a mismatched dT (ΔΔG(0)(310) was 7.6 or 6.8 kJ mol(-1), ΔΔH was 14 or 49 kJ mol(-1)), no such thermodynamic advantage was observed with the 1,2-d(GG) intrastrand cross-link of oxaliplatin at these positions (ΔΔG(0)(310) was 2.8 or -0.3 kJ mol(-1), ΔΔH was 4 or 9 kJ mol(-1)). The equilibrium thermodynamic data also provide insight into the processes associated with misincorporation of incorrect nucleotides during replication bypass across major cross-links of antitumor oxaliplatin. On the other hand, besides thermodynamic effects also kinetic factors play an important role in the processing of the cross-links of antitumor platinum drugs. The impact of the two effects in overall processing DNA adducts by a particular DNA polymerase will depend on its nature.     

Towards dual photodynamic and antiangiogenic agents: design and synthesis of a phthalocyanine-chalcone conjugate

A phthalocyanine-chalcone conjugate has been designed to combine the vascular disrupting effect of chalcones with the photodynamic effect of phthalocyanines. This potential dual photodynamic and antiangiogenic agent was obtained by the condensation of a tetrahydroxylated non-peripherally substituted Zn(ii) phthalocyanine with an amino chalcone converted into the corresponding activated isocyanate. The conjugate was fully characterized.     

peri-Dimethylamino substituent effects on proton transfer at carbon in α-naphthylacetate esters: a model for mandelate racemase

The rate constants for exchange of hydrogen for deuterium at the α-CH(2) positions of 8-(N,N-dimethylaminonaphthalen-1-yl)acetic acid tert-butyl ester 1 and naphthalen-1-ylacetic acid tert-butyl ester 2 have been determined in potassium deuteroxide solutions in 1 : 1 D(2)O : CD(3)CN, in order to quantify the effect of the neighbouring peri-dimethylamino substituent on α-deprotonation. Intramolecular general base catalysis by the (weakly basic) neighbouring group was not detected. Second-order rate constants, k(DO), for the deuterium exchange reactions of esters 1 and 2 have been determined as 1.35 × 10(-4) M(-1) s(-1) and 3.95 × 10(-3) M(-1) s(-1), respectively. The unexpected 29-fold decrease in the k(DO) value upon the introduction of a peri-dimethylamino group is attributed to an unfavourable steric and/or electronic substituent effect on intermolecular deprotonation by deuteroxide ion. From the experimental k(DO) values, carbon acid pK(a) values of 26.8 and 23.1 have been calculated for esters 1 and 2.     

Doped semimetal clusters: ternary, intermetalloid anions [Ln@Sn7Bi7]4- and [Ln@Sn4Bi9]4- (Ln = La, Ce) with adjustable magnetic properties

Two K([2.2.2]crypt) salts of lanthanide-doped semimetal clusters were prepared, both of which contain at the same time two types of ternary intermetalloid anions, [Ln@Sn(7)Bi(7)](4-) and [Ln@Sn(4)Bi(9)](4-), in 0.70:0.30 (Ln = La) or 0.39:0.61 (Ln = Ce) ratios. The cluster shells represent nondeltahedral, fullerane-type arrangements of 14 or 13 main group metal atoms that embed the Ln(3+) cations. The assignment of formal +III oxidation states for the Ln sites was confirmed by means of magnetic measurements that reveal a diamagnetic La(III) compound and a paramagnetic Ce(III) analogue. Whereas the cluster anions with a 14-atomic main-group metal cage represent the second examples in addition to a related Eu(II) cluster published just recently, the 13-atomic cages exhibit a yet unprecedented enneahedral topology. In contrast to the larger cages, which accord to the Zintl-Klemm-Busmann electron number-structure correlation, the smaller clusters require a more profound interpretation of the bonding situation. Quantum chemical investigations served to shed light on these unusual complexes and showed significant narrowing of the HOMO-LUMO gap upon incorporation of Ce(3+) within the semimetal cages.     

Spectroscopic methods in gas hydrate research

Gas hydrates are crystalline structures comprising a guest molecule surrounded by a water cage, and are particularly relevant due to their natural occurrence in the deep sea and in permafrost areas. Low molecular weight molecules such as methane and carbon dioxide can be sequestered into that cage at suitable temperatures and pressures, facilitating the transition to the solid phase. While the composition and structure of gas hydrates appear to be well understood, their formation and dissociation mechanisms, along with the dynamics and kinetics associated with those processes, remain ambiguous. In order to take advantage of gas hydrates as an energy resource (e.g., methane hydrate), as a sequestration matrix in (for example) CO₂ storage, or for chemical energy conservation/storage, a more detailed molecular level understanding of their formation and dissociation processes, as well as the chemical, physical, and biological parameters that affect these processes, is required. Spectroscopic techniques appear to be most suitable for analyzing the structures of gas hydrates (sometimes in situ), thus providing access to such information across the electromagnetic spectrum. A variety of spectroscopic methods are currently used in gas hydrate research to determine the composition, structure, cage occupancy, guest molecule position, and binding/formation/dissociation mechanisms of the hydrate. To date, the most commonly applied techniques are Raman spectroscopy and solid-state nuclear magnetic resonance (NMR) spectroscopy. Diffraction methods such as neutron and X-ray diffraction are used to determine gas hydrate structures, and to study lattice expansions. Furthermore, UV-vis spectroscopic techniques and scanning electron microscopy (SEM) have assisted in structural studies of gas hydrates. Most recently, waveguide-coupled mid-infrared spectroscopy in the 3–20 μm spectral range has demonstrated its value for in situ studies on the formation and dissociation of gas hydrates. This comprehensive review summarizes the importance of spectroscopic analytical techniques to our understanding of the structure and dynamics of gas hydrate systems, and highlights selected examples that illustrate the utility of these individual methods.     

Zinc chalcogenolate complexes as precursors to ZnE and Mn/ZnE (E = S, Se) clusters

The ternary clusters (tmeda)(6)Zn(14-x)Mn(x)S(13)Cl(2) (1a-d) and (tmeda)(6)Zn(14-x)Mn(x)Se(13)Cl(2) (2a-d), (tmeda = N,N,N',N'-tetramethylethylenediamine; x ≈ 2-8) and the binary clusters (tmeda)(6)Zn(14)E(13)Cl(2) (E = S, 3; Se, 4;) have been isolated by reacting (tmeda)Zn(ESiMe(3))(2) with Mn(II) and Zn(II) salts. Single crystal X-ray analysis of the complexes confirms the presence of the six "(tmeda)ZnE(2)" units as capping ligands that stabilize the clusters, and distorted tetrahedral geometry around the metal centers. Mn(II) is incorporated into the ZnE framework by substitution of Zn(II) ions in the cluster. The polynuclear complexes (tmeda)(6)Zn(12.3)Mn(1.7)S(13)Cl(2)1a, (tmeda)(6)Zn(12.0)Mn(2.0)Se(13)Cl(2)2a, and (tmeda)(6)Zn(8.4)Mn(5.6)Se(13)Cl(2)2d represent the first examples of "Mn/ZnE" clusters with structural characterization and indications of the local chemical environment of the Mn(II) ions. The incorporation of higher amounts of Mn into 1d and 2d has been confirmed by elemental analysis. Density functional theory (DFT) calculations indicate that replacement of Zn with Mn is perfectly feasible and at least partly allows for the identification of some sites preferred by the Mn(II) metals. These calculations, combined with luminescence studies, suggest a distribution of the Mn(II) in the clusters. The room temperature emission spectra of clusters 1c-d display a significant red shift relative to the all zinc cluster 3, with a peak maximum centered at 730 nm. Clusters 2c-d display a peak maximum at 640 nm in their emission spectra.     

Nature and structure of aluminum surface sites grafted on silica from a combination of high-field aluminum-27 solid-state NMR spectroscopy and first-principles calculations

The determination of the nature and structure of surface sites after chemical modification of large surface area oxides such as silica is a key point for many applications and challenging from a spectroscopic point of view. This has been, for instance, a long-standing problem for silica reacted with alkylaluminum compounds, a system typically studied as a model for a supported methylaluminoxane and aluminum cocatalyst. While (27)Al solid-state NMR spectroscopy would be a method of choice, it has been difficult to apply this technique because of large quadrupolar broadenings. Here, from a combined use of the highest stable field NMR instruments (17.6, 20.0, and 23.5 T) and ultrafast magic angle spinning (>60 kHz), high-quality spectra were obtained, allowing isotropic chemical shifts, quadrupolar couplings, and asymmetric parameters to be extracted. Combined with first-principles calculations, these NMR signatures were then assigned to actual structures of surface aluminum sites. For silica (here SBA-15) reacted with triethylaluminum, the surface sites are in fact mainly dinuclear Al species, grafted on the silica surface via either two terminal or two bridging siloxy ligands. Tetrahedral sites, resulting from the incorporation of Al inside the silica matrix, are also seen as minor species. No evidence for putative tri-coordinated Al atoms has been found.     

Preparation,Structure, and Reactivity of Thioxo and Imino Derivatives of the Triolide (and Pentolide) from (R)-3-Hydroxybutanoic Acid

Reaction of the triolide 1 from (R)-3-hydroxybutanoic acid with Lawesson's reagent 5 leads to the mono-, di-, and trithio derivatives 6–8 which can be isolated in pure form (20–40% yields), and which have crystal structures very similar to the parent triolide 1 (Fig. 1). Similarly, pentolide 3 is converted to mixtures of various thio derivatives, three of which are separated ( 10–12 ) by HPLC and fully characterized. The X-ray structures of the mono- and of one of the dithiopentolides ( 10, 12 ) differ remarkably from each other (Fig. 3). Reduction of the thiotriolides 6–8 (NaBH₄, R₃SnH, Cl₃SiH, Raney-Ni) gives 12-membered rings containing up to three ether groups (chiral crown ethers, 15, 17–19 ) in poor yields. The thiotriolides react spontaneously and in yields of up to 96% with ammonia, certain primary amines, and hydroxylamine to give imine and oxime derivatives with intact 12-membered-ring backbones ( 20, 22–24, 30 , see crystal structures in Figs. 4–7). The rigid structure of all the derivatives of triolide 1 puts the C?O, C?S, and C?NR O-, S-, and N-atoms in juxtaposition (a feature reminiscent of the side chains in the iron-binder enterobactin, Fig. 6). Imines containing PPh₂ groups are prepared ( 30, 33, 35 ) from the thiotriolides and tested as chiral ligands for Pd^II-catalyzed 1,3-diphenyallylations (→ 37 , enantiomer ratio up to 77:23). The reactions described demonstrate that multiple reactions of the triolide 1 from (R)-3-hydroxybutanoic acid which proceed through tetrahedral intermediates are possible without ring opening – the skeleton is remarkably stable, and this might be exploited as a template for bringing up to three pendent substituents into close proximity to allow a study of their interactions and cooperative properties. Also, the di- and trithio derivatives 7 and 8 could be used for cross-linking in molecules containing primary NH₂ groups.     

Binuclear rhodium(II) complexes with leucine and proline

The dimeric rhodium(II) complexes [Rh₂(leu)₄(H₂O)₂]- (ClO₄)₄ and [Rh₂(pro)₄(H₂O)₂](ClO₄)₄ have been prepared and characterized by elemental analyses, i.r., u.v.–vis. and ¹H-n.m.r. spectroscopy. The amino acid molecules are coordinated as bridging ligands via their carboxylato groups. Cyclic voltammetry in DMF has shown that the complexes undergo a quasi-reversible reduction to yield dimers containing a Rh ₂ ³⁺ core. Oxidation processes within the 0–1.5V range were not observed.