Carbohydrate-based DNA ligands: sugar-oligoamides as a tool to study carbohydrate-nucleic acid interactions

Sugar-oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate-DNA interactions. The general design of the ligands 1-3 has been done as to favor the bound conformation of Distamycin-type gamma-linked covalent dimers which is a hairpin conformation. Indeed, NMR analysis of the sugar-oligoamides in the free state has indicated the presence of a percentage of a hairpin conformation in aqueous solution. The DNA binding activity of compounds 1-3 was confirmed by calf thymus DNA (ct-DNA) NMR titration. Interestingly, the binding of the different sugar-oligoamides seems to be modulated by the sugar configuration. Semiquantitative structural information about the DNA ligand complexes has been derived from NMR data. A competition experiment with Netropsin suggested that the sugar-oligoamide 3 bind to DNA in the minor groove. The NMR titrations of 1-3 with poly(dA-dT) and poly(dG-dC) suggested preferential binding to the ATAT sequence. TR-NOE NMR experiments for the sugar-oligoamide 3-ct-DNA complex both in D(2)O and H(2)O have confirmed the complex formation and given information on the conformation of the ligand in the bound state. The data confirmed that the sugar-oligoamide ligand is a hairpin in the bound state. Even more relevant to our goal, structural information on the conformation around the N-glycosidic linkage has been accessed. Thus, the sugar asymmetric centers pointing to the NH-amide and N-methyl rims of the molecule have been characterized.     

Rare earth metal complexes with 1,3-bis-(2-hydroxyphenyl)-1,3-propanedione. An example of anhydrous rare earth β-diketonates

Summary The interaction of non-anhydrous solutions of the ligand 1,3-bis-(2-hydroxyphenyl)-1,3-propanedione (bhppH₃) with hydrated rare earth chlorides resulted in the formation of anhydrous, non-solvated, complexes M(bhppH₂)₃ (M=Y, La, Nd, Pr, Sm or Yb). The complexes have been characterized by elemental analysis, t.g., i.r. and¹H n.m.r. spectroscopy. The evidence suggests that the coordination is through the -diketone site.     

Unexpected ferromagnetic interaction in a new tetranuclear copper(II) complex: synthesis, crystal structure, magnetic properties, and theoretical studies

The new tetranuclear carbonate complex [Cu2L)2(CO3)] x 8H2O (1 x 8H2O) (H3L = (2-(2-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine) has been obtained by two different synthetic routes and fully characterized. Recrystallization of 1 x 8H2O in methanol yields single crystals of {[(Cu2L)2(CO3)]}2 x 12H2O (1 x 6H2O), suitable for X-ray diffraction studies. The crystal structure of 1 x 6H2O shows two crystallographically different tetranuclear molecules in the asymmetric unit, 1a and 1b. Both molecules can be understood as self-assembled from two dinuclear [Cu2L]+ cations, joined by a mu4-eta(2):eta(1):eta(1) carbonate ligand. The copper atoms of each crystallographically different [(Cu2L)2(CO3)] molecule present miscellaneous coordination polyhedra: in both 1a and 1b, two metal centers are in square pyramidal environments, one displays a square planar chromophore and the other one has a geometry that can be considered as an intermediate between square pyramid and trigonal bipyramid. Magnetic studies reveal net intramolecular ferromagnetic coupling between the metal atoms. Density functional calculations allow the assignment of the different magnetic coupling constants and explain the unexpected ferromagnetic behavior, because of the presence of an unusual NCN bridging moiety and countercomplementarity of the phenoxo (or carbonate) and NCN bridges.     

Are electrocyclization reactions of (3Z)-1,3,5-hexatrienone and nitrogen derivatives pseudopericyclic? A DFT study

[reactions: see text] Electrocyclization reactions of (3Z)-1,3,5-hexatrienone and nitrogen derivatives were studied by performing density functional theory (DFT) calculations together with the 6-31+G* basis set. Reactants, products, and transition states for each reaction were localized and the IRC connecting reactants and products was also obtained. Magnetic properties were evaluated along the reaction path to elucidate the characteristics of the reactions studied. As obtained from the calculations, electrocyclization of (3Z)-1,3,5-hexatrienone is a pericyclic process, as indicated by a variety of indexes, such as Nucleus Independent Chemical Shift (NICS), anisotropy of the magnetic susceptibility, or anisotropy of the current-induced density (ACID). This reaction presents characteristics of pericyclic reactions despite the activation energy lowering relative to the electrocyclization of (4Z)-1,2,4,6-heptatetraene, and the relatively small NICS values observed in the transition state. Magnetic properties indicate that an enhancement of the aromaticity relative to reactants and products occurs revealing the absence of orbital disconnections on the cyclic loop of interacting orbitals. Only two reactions among those studied exhibit pseudopericyclic character due to the in-plane attack of the lone pair on nitrogen. In these cases, the reactions showed no barrier for the electrocyclization process, and no aromaticity enhancement was observed.     

Synthesis and structure of the incomplete cuboidal clusters [W3Se4H3(dmpe)3]+, [W3Se4H(3-x)(OH)x(dmpe)3]+ and [W3Se4(OH)3(dmpe)3]+, and the mechanism of the acid-assisted substitution of the coordinated hydrides

The novel incomplete cuboidal cluster [W3Se4H3(dmpe)3](PF6), [1](PF6), has been prepared by reduction of [W3Se4Br3(dmpe)3](PF6) with LiBH4 in THF solution. The trihydroxo complex [W3Se4(OH)3(dmpe)3](PF6), [2](PF6), was obtained by reacting [W3Se4Br3(dmpe)3](PF6) with NaOH in MeCN-H2O solution. The complexes [1](PF6) and [2](PF6) were converted to their BPh4- salts by treatment with NaBPh4. Recrystallisation of [1](BPh4) in the presence of traces of water affords the mixed dihydride hydroxo complex [W3Se4H2(OH)(dmpe)3](BPh4). The crystal structures of [1](BPh4), [2](BPh4) and [W3Se4H2(OH)(dmpe)3](BPh4) have been resolved. Although the [1]+ trihydride does not react with an excess of halide salts, reaction with HX leads to [W3Se4X3(dmpe)3]+ (X = Cl, Br). The kinetics of this reaction has been studied at 25 degrees C in MeCN-H2O solution (1:1, v/v) and found to occur with two consecutive kinetic steps. The first step is independent of the nature and concentration of the X(-) anion but shows a first order dependence on the concentration of acid (k1 = 12.0 mol(-1) dm(3) s(-1)), whereas the second one is independent of the nature and concentration of both the acid and added salts (k2 = 0.024 s(-1)). In contrast, the reaction of [2]+ with acids occurs in a single step with kobs = 0.63 s(-1)(HCl) and 0.17 s(-1)(HBr). These kinetic results are discussed on the basis of the mechanism previously proposed for the reactions of the analogous [W3S4H3(dmpe)3]+ cluster, with special emphasis on the effects caused by the change of S by Se on the rate constants for the different processes involved.     

Rapid determination of minority organic acids in honey by high-performance liquid chromatography

A rapid high-performance liquid chromatographic method for the determination of organic acids in honey is reported. Malic, maleic, citric, succinic and fumaric acids were identified and quantified in 15 min. First time repeatibility, reproducibility and recoveries were determined out for these acids in honey samples. Maleic acid was also quantified for first time by a chromatographic method. The organic acids were removed from honey by using a solid-phase extraction procedure with anion-exchange cartridges. Previously, the solution of honey was adjusted to pH 10.50 with 0.1 M NaOH and stirred for 15 min at room temperature. Then, this solution was adjusted to pH 5.00 with 0.1 M H2SO4. This procedure was carried out to avoid interferences in the baseline. The chromatographic separation was achieved with only one Spherisorb ODS-2 S5 column thermostated at 25 degrees C. Metaphosphoric acid (pH 2.20) was used as mobile phase at a flow-rate of 0.7 ml/min. Organic acids were detected with a UV-vis detector (215 nm). The precision results showed that the relative standard deviations of the repeatability and reproducibility were < or =3.20% and < or =4.86%, respectively. The recoveries of the organic acids ranged from 62.9 to 99.4%. Under optimum conditions the detection limits ranged from 0.0064 to 7.57 mg/kg and the quantification limits ranged from 0.025 to 10.93 mg/kg.     

Accurately solving the electronic Schrodinger equation of small atoms and molecules using explicitly correlated (r12-)MR-CI. VIII. Valence excited states of methylene (CH2)

We compute the adiabatic transition energies of methylene (CH(2)) from the ground state to the lowest electronically excited valence states using the r(12)-MR-ACPF-2 method with a large basis set and an extended reference space. We recall that this method aims at reaching the basis-set and full configuration interaction (CI) limits simultaneously. Our best excitation energies, T(e) (T(0)), are 9.22 (8.87) (a (1)A(1), corrected for relativistic and adiabatic effects), 31.98 (31.86) (b (1)B(1)), and 57.62 (57.18) kcal mol(-1) (c (1)A(1)) (both uncorrected). We are able to reach the respective basis-set limits that closely that the remaining errors of our (uncorrected) calculations are clearly due to the MR-ACPF-2 method. While we are unable to assess the error of the latter method in a systematic way, we still believe that it is rather unlikely that the errors of our excitation energies exceed +/-0.10 kcal mol(-1). We finally observe that our (corrected) a state values deviate by only -0.10 (-0.10) kcal mol(-1) from the results of Csaszar et al. [J. Chem. Phys. 118, 10631 (2003)]--who did careful extrapolations to the valence full-CI and basis-set limits and added a correction for the core correlation--and that the deviation from experiment is only -0.13 (-0.13) kcal mol(-1). From these excellent agreements we conclude that our excitation energies to the b and c states are similarly accurate.     

Reactivity of amino acids in nitrosation reactions and its relation to the alkylating potential of their products

Nitrosation reactions of amino acids with an -NH(2) group [namely, six alpha-amino acids (glycine, alanine, alpha-aminobutyric acid, alpha-aminoisobutyric acid, valine, and norvaline); two beta-amino acids (beta-alanine and beta-aminobutyric acid), and one gamma-amino acid (gamma-aminobutyric acid)] were studied. Nitrosation was carried out in aqueous acid media, mimicking the conditions of the stomach lumen. The rate equation was r = k(3)(exp)[amino acid][nitrite](2), with a maximum k(3)(exp) value in the 2.3-2.7 pH range. The existence of an isokinetic relationship supports the argument that all the reactions share a common mechanism. A nitrosation mechanism is proposed, and the following conclusions are drawn: (i) Nitrosation reactions of amino acids with a primary amino group in acid media occur with dinitrogen trioxide as the main nitrosating agent. The finding that the nitrosation rate is proportional to the square of the nitrite concentration suggests that the yield of nitrosation products in the stomach would increase sharply with higher nitrate/nitrite intakes. (ii) Stomach hypochlorhydria could be a potential enhancer of in vivo amino acid nitrosation. (iii) The reactivity (k(3)()(exp)) [alpha-amino acids > beta-amino acids > gamma-amino acids] is the same as that found in a previous work for the alkylating potential of lactones formed from nitrosation products of the same amino acids. This implies that the nitrosation reactions of the most common natural amino acids are the most efficient precursors of the most powerful alkylating agents. (iv) The order of magnitude (10(7)-10(8) M(-1) s(-1)) of the bimolecular rate constants of nitrosation shows that such reactions occur through an encounter process.