Antitumor Effect of Zwitterions of Imidazolium Derived from L-methionine in BALB/c Mice with Lymphoma L5178Y.

BACKGROUND: In the therapy of cancer, several treatments have been designed using nanomaterials, among which gold nanoparticles (AuNPs) have been featured as a promising antitumoral agent. Our research group has developed the synthesis of gold nanoparticles L-AuNPs and D-AuNPs stabilized with zwitterions of imidazolium (L-1 and D-1) derived from L-methionine and D-methionine. Because the stabilizer agent is chiral, we observed through circular dichroism that AuNPs also present chirality; such chirality as well as the fact that the stabilizing agent contains fragments of methionine and imidazolium that are commonly involved in biological processes, opens up the possibility that this system may have biological compatibility. Additionally, the presence of methionine in the stabilizing agent opens the application of this system as a possible antitumor agent because methionine is involved in methylation processes of molecules such as DNA. OBJECTIVE: The aim of this research is the evaluation of the antitumor activity of gold nanoparticles stabilized with zwitterions of imidazolium (L-AuNPs) derived from L-methionine in the model of BALB/c mice with lymphoma L5178Y. METHODS: Taking as a parameter cell density, the evaluation of the inhibitory effect of L-AuNPs was carried out with a series of in vivo tests in BALB/c type mice; three groups of five mice each were formed (Groups 1, 2 and 3); all mice were i.p. inoculated with the lymphoblast murine L5178Y. Group 1 consisted of mice without treatment. In the Groups 2 and 3 the mice were treated with L-AuNPs at 0.3 mg/Kg on days 1, 7 and 14 by orally and intraperitonally respectively. RESULTS: These results show low antitumor activity of these gold nanoparticles (L-NPsAu) but interestingly, the imidazolium stabilizing agent of gold nanoparticle (L-1) displayed promising antitumor activity. On the other hand, the enantiomer of L-1, (D-1) as well as asymmetric imidazole derivate from L-methionine (L-2), do not exhibit the same activity as L-1. CONCLUSION: The imidazolium stabilizing agent (L-1) displayed promising antitumor activity. Modifications in the structure of L-1 showed that, the stereochemistry (like D-1) and the presence of methionine fragments (like L-2) are determinants in the antitumor activity of this compound.

Reliable change indices for the 37-item version of the MMSE in Spanish older adults.

OBJECTIVE: The aim of this study was to establish reliable change and regression-based change score norms on the 37-item version of MMSE in older Spanish adults at the three-year follow-up. METHOD: All subjects of this research were selected from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort study of older adults (65 years and over). Of the 4208 individuals free from neurological disorders in this cohort, 2073 participants completed the MMSE-37 at baseline and at the three-year follow-up. Reliable Change Indices were computed for the 80, 90% and 95 confidence intervals (CIs). Multiple regression analyses were used to derive equations for predicting MMSE-37 post-test scores taking into account baseline scores, time to follow-up and sociodemographic factors. RESULTS: The MMSE-37 obtained a marginal test-retest reliability (.70). The results showed significant effects of education, age, and sex on the MMSE-37 change scores. After correcting for regression to the mean, at least a 6-point change on MMSE-37 (three-years follow-up) is required to be classified as reliable (90% CI). CONCLUSIONS: These findings demonstrate that the MMSE-37 is a reliable test-retest measure whose change scores are significantly influenced by sociodemographic factors. Importantly, small changes on this measure require a cautious interpretation.

From metallic gold to [Au(NHC)2]+ complexes: an easy, one-pot method.

A simple and direct method is described to prepare cationic bis(NHC)-Au(i) complexes containing N-alkyl or N-aryl NHC ligands to generate relevant gold complexes using metallic gold as the starting material.

Chiral Imidazolium-Functionalized Au Nanoparticles: Reversible Aggregation and Molecular Recognition.

Gold nanoparticles (AuNPs) stabilized by imidazolium salts derived from amino acids [glycine (1), rac-alanine (2), l-phenylalanine (3), and rac-methionine (4)] were prepared. The AuNPs were stabilized the most by 4, which kept the particles dispersed in water for months at pH > 5.5. These AuNPs exhibited a well-defined absorption band at 517 nm and had an average particle size of 11.21 ± 0.07 nm. The 4-AuNPs were reversibly aggregated by controlling the pH of the solution. Chiral R,R-4-AuNPs and S,S-4-AuNPs were synthesized, and the chiral environment on the nanoparticle surface was confirmed using circular dichroism; these nanoparticles exhibited a molecular recognition of chiral substrates. Furthermore, they showed potential for separating racemic mixtures when supported on a layered double hydroxide.

Calix[4]arenes of aluminum and gallium with benzimidazolyl ligands: steric control of the conformation via substitution on the ligand.

Complexes [bzimAlR(2)](4) [bzim = benzimidazolate; R = Et (2), (i)Bu (3)], [mbzimAlR(2)](4) [mbzim = 2-methylbenzimidazolate; R = Et (6), (i)Bu (7)], [dmbzimAlR(2)](4) [dmbzim = 5,6-dimethylbenzimidazolate; R = Me (9), Et (10), (i)Bu (11)], and [tmbzimAlR(2)](4) [tmbzim = 2,5,6-trimethylbenzimidazolate; R = Me (12), Et (13), (i)Bu (14)] have been prepared via alkane elimination and coordinative self-assembly upon the reaction of benzimidazole ligands with aluminum alkyls in benzene, toluene, or xylene. Characterization of the complexes was achieved by spectroscopic methods, microanalysis, and X-ray crystallography of 2, 7, 10, 11, 13, and 14. The complexes reported herein and the aluminum and gallium analogues 1, 4, 5, and 8 reported in a previous paper (1) are predominantly tetranuclear aggregates related to calix[4]arenes in which the benzimidazolyl ligands bind two metal atoms in a η(1):η(1) fashion. X-ray crystallography demonstrates that modulation of the conformation adopted by these metallacalix[4]arenes is achieved by proper substitution on the C atom at the 2 position of the benzimidazolyl ligand. An H substituent for 1, 2, 4, 10, and 11 favors a chair conformation with a small cavity and approximate C(2h) symmetry, while a CH(3) substituent for 5, 7, 8, 13, and 14 introduces enough repulsion to switch the conformation to a 1,3-alternate or double cone with a concomitant larger cavity and approximate C(2v) symmetry.

Aluminium complexes derived from tridentate thioetherbis(phenolate) ligands and their activity in Diels-Alder catalysis.

Organoaluminium(III) thioetherbis(phenolate) complexes derived from 2,2-thiobis(4,6-diterbuthylphenolate) (Stdiol) and 2,2-thiobis(4,6-dimethylphenolate) (Smdiol) were prepared by reaction of AlMe3 with the diol proligands LH2 (SmdiolH2, StdiolH2). Monomeric complexes of general formulae [LAlR(L)] (L = Stdiol, R = Me, L = THF (1); L = Stdiol, R = Me, L = Et2O (2); L = Stdiol, R = iBu, L = THF) (3); L = Smdiol, R = Me, L = THF (4); L = Smdiol, R = iBu, L = THF (5)) and [LAlCl(THF)] (L = Stdiol (6); L = Smdiol (7)) were obtained when the reactions were performed in THF or Et2O in hexane or toluene, species of formulae [(L2Al)AlR2] (L = Stdiol, R = Me (8); L = Stdiol, R = iBu (9); L = Smdiol, R = Me (10)) were formed as evidenced by spectroscopic methods. Crystals suitable for X-ray diffraction studies were obtained for 2, 3, 4, 6, 8, 9 and 10. In these cases the sulfur atom coordinates to the aluminium center with Al-S bond lengths between 2.43-2.75 A adopting boat-boat conformations. Compounds 1, 3, 4, and 8 were tested in the catalytic Diels-Alder cycloaddition reaction between methacrolein and cyclopentadiene showing excellent regioselectivities with good conversion yields.

Dichloro and alkylchloro gallium derivatives of dichalcogenoimidodiphosphinate ligands: isolation of a spirogallium cation.

Dichloro and chloromethyl Ga(III) complexes of general formulae [XClGa-eta2-{R2P(E)NP(E'R'2-E,E'}](X = Cl, R, R'= Ph, E, E'= O (1), S (2), Se (3); R = Ph, R'= OEt, E = O, E'= S (4); R = Me, R'= Ph, E, E'= S (5) and X = Me, E, E'= O (6), S (7), Se (8)) were synthesised by either metathesis reactions between GaCl3 and the potassium salt of the ligand (X = Cl) or by methane eliminations from in situ prepared GaMe2Cl and the protonated ligands LH (X = Me). Redistribution reaction of (3) in either CDCl3 or THF afforded the solvent-free tetracoordinate gallium spirocycle cation [Ga-{eta2-{Ph2P(Se)NP(Se)Ph2-Se,Se'})2]+ (9+). The molecular structures of complexes 2, 4, 5, 7 and 9(+) show non-planar gallacycle rings.